Difference between revisions of "Cervical cancer"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|gyn}} | |
− | + | ''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Cervical_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Cervical cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | |
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+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==[https://www.asco.org/ ASCO]== | ||
+ | *'''2022:''' Chuang et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8920468/ Management and Care of Patients With Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update] [https://pubmed.ncbi.nlm.nih.gov/35245079/ PubMed] | ||
+ | **'''2016:''' Chuang et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5493265/ Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/28717717/ PubMed] | ||
− | + | ==[https://www.esmo.org/ ESMO]== | |
− | ==[ | + | *'''2018:''' Marth et al. [https://doi.org/10.1093/annonc/mdy160 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/29741577/ PubMed] |
− | *''' | + | **'''2017:''' Marth et al. [https://doi.org/10.1093/annonc/mdx220 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/28881916/ PubMed] |
− | + | **'''2012:''' Colombo et al. [https://doi.org/10.1093/annonc/mds268 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/22997451 PubMed] | |
− | *'''2012:''' Colombo et al. [ | + | **'''2010:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdq162 Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555099/ PubMed] |
− | + | **'''2009:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdp119 Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454454/ PubMed] | |
− | *[https://www.nccn.org/ | + | **'''2008:''' Haie-Meder et al. [https://doi.org/10.1093/annonc/mdn112 Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456752/ PubMed] |
+ | |||
+ | ==NCCN== | ||
+ | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426 NCCN Guidelines - Cervical Cancer] | ||
+ | **'''2019:''' Koh et al. [https://doi.org/10.6004/Jnccn.2019.0001 Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/30659131/ PubMed] | ||
+ | **'''2015:''' Koh et al. [https://doi.org/10.6004/jnccn.2015.0055 Cervical Cancer, Version 2.2015] [https://pubmed.ncbi.nlm.nih.gov/25870376/ PubMed] | ||
+ | **'''2013:''' Koh et al. [https://doi.org/10.6004/Jnccn.2013.0043 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/23486458/ PubMed] | ||
+ | **'''2010:''' Greer et al. [https://doi.org/10.6004/Jnccn.2010.0104 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/21147903/ PubMed] | ||
+ | **'''2008:''' Greer et al. [https://doi.org/10.6004/Jnccn.2008.0003 Cervical cancer.] [https://pubmed.ncbi.nlm.nih.gov/18267056/ PubMed] | ||
+ | **'''2004:''' Teng et al. [https://doi.org/10.6004/Jnccn.2004.0051 Cervical cancer guidelines. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19780304/ PubMed] | ||
=Neoadjuvant chemotherapy= | =Neoadjuvant chemotherapy= | ||
==Cisplatin & Paclitaxel {{#subobject:fdd2df|Regimen=1}}== | ==Cisplatin & Paclitaxel {{#subobject:fdd2df|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:7b5fcb|Variant=1}}=== | ===Regimen {{#subobject:7b5fcb|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2003.09.015 Park et al. 2004] |
− | |style="background-color:#91cf61"|Phase | + | |2000-10 to 2002-01 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second''' | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second''' | ||
*[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first''' | *[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 12 and 6 hours prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 12 and 6 hours prior to | + | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to | ||
*[[:Category:Emesis_prevention|Antiemetics]] before and 3 days after chemotherapy | *[[:Category:Emesis_prevention|Antiemetics]] before and 3 days after chemotherapy | ||
− | |||
'''10-day cycle for 3 cycles''' | '''10-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*Clinical response assessed after 3 cycles with pelvic examination and MRI. Treatment followed by [[Surgery#Cervical_cancer_surgery|surgery]] or radiation therapy. | *Clinical response assessed after 3 cycles with pelvic examination and MRI. Treatment followed by [[Surgery#Cervical_cancer_surgery|surgery]] or radiation therapy. | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. [https://doi.org/10.1016/j.ygyno.2003.09.015 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14751139/ PubMed] | ||
+ | =Definitive therapy for locally advanced disease= | ||
+ | ==Brachytherapy protocol {{#subobject:ea73cc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen=== | ||
+ | To be completed | ||
+ | ====Radiotherapy==== | ||
+ | *[[Brachytherapy|Intracavitary brachytherapy with radium or its equivalent]] by the following study-specific criteria: | ||
+ | **Pearcey et al. 2002: See paper for details | ||
+ | **GOG 120, stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A | ||
+ | ***Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy | ||
+ | **B9E-MC-JHQS & Sehouli et al. 2012: 30 to 3500 cGy delivered to point A | ||
+ | **GOG 219: 35 to 4360 cGy to point A | ||
+ | **GOG 120, stage IIB: 4000 cGy for a total dose of 8080 cGy to point A | ||
+ | ***Patients that could not receive brachytherapy underwent additional external_beam_radiotherapy for a total dose of 6120 cGy | ||
+ | **GOG 123: 3000 cGy to point A for a total dose of 7500 cGy | ||
+ | **GOG 165: ONE of the following: | ||
+ | ***Low-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 4000 cGy to point A given in 1 to 2 fractions | ||
+ | ***High-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT | ||
+ | **GOG 165: Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078] |
− | |||
==Carboplatin & RT {{#subobject:ea866d|Regimen=1}}== | ==Carboplatin & RT {{#subobject:ea866d|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | Carboplatin & RT: Carboplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, AUC-based carboplatin {{#subobject:e0ewe0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(23)00479-5 Monk et al. 2023 (CALLA)] | ||
+ | |2019-02-15 to 2020-12-10 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Durvalumab.2C_RT_999|Carboplatin, Durvalumab, RT]]<br>1b. [[#Cisplatin.2C_Durvalumab.2C_RT_999|Cisplatin, Durvalumab, RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ===Regimen {{#subobject:e0e770|Variant=1}}=== | + | ====Chemotherapy==== |
+ | *[[Carboplatin (Paraplatin)]] AUC 2 IV once per day on days 1, 8, 15, 22, 29 | ||
+ | ====Radiotherapy==== | ||
+ | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 180 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions) | ||
+ | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Brachytherapy_protocol|Brachytherapy]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, BSA-based carboplatin {{#subobject:e0e770|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.ygyno.2006.06.045 Veerasarn et al. 2006] |
|2001-2003 | |2001-2003 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Carboplatin, UFT, RT | + | |[[#Carboplatin.2C_UFT.2C_RT_999|Carboplatin, UFT, RT]] |
− | | style="background-color:#ffffbf" |Did not meet primary endpoints of TTP/OS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of TTP/OS |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once on | + | *[[Carboplatin (Paraplatin)]] 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, +/- 36 |
− | |||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Concurrent [[External_beam_radiotherapy|radiation therapy]] | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | ||
− | + | '''5- to 6-week course''' | |
− | ''' | + | </div></div> |
===References=== | ===References=== | ||
− | # Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P, Suntornpong N, Sangruchi S, Lertsanguansinchai P, Khorprasert C, Sookpreedee L, Udompunturak S. A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results. Gynecol Oncol. 2007 Jan;104(1):15-23. Epub 2006 Sep 25. [https:// | + | # Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P, Suntornpong N, Sangruchi S, Lertsanguansinchai P, Khorprasert C, Sookpreedee L, Udompunturak S. A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results. Gynecol Oncol. 2007 Jan;104(1):15-23. Epub 2006 Sep 25. [https://doi.org/10.1016/j.ygyno.2006.06.045 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16996583/ PubMed] |
− | + | # '''CALLA:''' Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. [https://doi.org/10.1016/s1470-2045(23)00479-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38039991/ PubMed] [https://clinicaltrials.gov/study/NCT03830866 NCT03830866] | |
==Cisplatin & RT {{#subobject:89c649|Regimen=1}}== | ==Cisplatin & RT {{#subobject:89c649|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen variant #1, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, weekly cisplatin x 5, no cap + 4500 cGy {{#subobject:72453d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1200/jco.22.02852 Kenter et al. 2023 (EORTC-55994)] | |
− | | | + | |2002-05 to 2014-01 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | | | + | |Neoadjuvant chemotherapy, then surgery |
− | |style="background-color:#ffffbf"|Did not meet primary | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS60 |
|- | |- | ||
− | | | + | |[https://doi.org/10.1016/s1470-2045(23)00479-5 Monk et al. 2023 (CALLA)] |
− | |style="background-color:# | + | |2019-02-15 to 2020-12-10 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Durvalumab.2C_RT_999|Carboplatin, Durvalumab, RT]]<br>1b. [[#Cisplatin.2C_Durvalumab.2C_RT_999|Cisplatin, Durvalumab, RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV | + | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | ====Radiotherapy | + | ====Radiotherapy==== |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 1 | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | + | **Total number of fractions: 25 | |
− | '''5-week course | + | **Total dose: 4500 cGy |
− | + | '''5-week course''' | |
− | ==== | + | </div> |
− | * | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | + | ====Subsequent treatment==== | |
− | + | *Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details) | |
− | ===Regimen variant #2, | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly cisplatin x 5, no cap + 5000 cGy {{#subobject:72d63d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.radonc.2016.02.010 Lutgens et al. 2016 (RADCHOC)] |
− | | | + | |2003-2009 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Hyperthermia_.26_RT_999|RT-HT]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS |
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885185/ Shrivastava et al. 2018 (CRACx)] |
− | | | + | |2003-2011 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[# | + | |[[Cervical_cancer_-_historical#Radiation_therapy|RT]] |
− | |style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint)<br>OS60: 54% vs 46%<br>(HR 0.82, 95% CI 0.68-0.98) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> | + | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | ==== | + | ====Supportive therapy==== |
− | * | + | *[[Ondansetron (Zofran)]] 16 mg (route not specified) once on day 1, prior to cisplatin |
− | + | *[[Dexamethasone (Decadron)]] 8 mg (route not specified) once on day 1, prior to cisplatin | |
− | + | *Pre- and post- cisplatin [[:Category:Hydration|hydration]] | |
− | ====Radiotherapy | + | ====Radiotherapy==== |
− | * | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | + | **Total number of fractions: 25 | |
− | ** | + | **Total dose: 5000 cGy |
− | ** | + | '''5-week course''' |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details) |
− | + | </div></div><br> | |
− | ===Regimen variant #3, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #3, weekly cisplatin x 6, no cap {{#subobject:63d249|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2002.20.4.966 Pearcey et al. 2002] | ||
+ | |1991-1996 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Cervical_cancer_-_historical#Radiation_therapy|RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS36 | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1056/NEJM199904153401502 Rose et al. 1999 (GOG 120)] | ||
+ | |rowspan=2|1992-1997 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Hydroxyurea.2C_RT|Cisplatin, Fluorouracil, Hydroxyurea, RT]] | ||
+ | |style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS | ||
+ | |- | ||
+ | |2. [[#Hydroxyurea_.26_RT|Hydroxyurea & RT]] | ||
+ | |style="background-color:#1a9850"|Superior OS (co-primary endpoint) | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)] | ||
+ | |2002-2004 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_RT|Cisplatin, Gemcitabine, RT]] | ||
+ | |style="background-color:#fc8d59"|Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdr628 Sehouli et al. 2012] | ||
+ | |2003-2008 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Paclitaxel_999|Carboplatin & Paclitaxel]], then [[Cervical_cancer_-_historical#Radiation_therapy|RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2013.50.1205 Zuliani et al. 2014] | ||
+ | |2003-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Cervical_cancer_-_historical#Radiation_therapy|RT]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>(HR 0.53, 95% CI 0.31-0.92) | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912330/ DiSilvestro et al. 2014 (GOG 219)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912330/ DiSilvestro et al. 2014 (GOG 219)] | ||
|2006-2009 | |2006-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Cisplatin, Tirapazamine, RT | + | |[[#Cisplatin.2C_Tirapazamine.2C_RT_999|Cisplatin, Tirapazamine, RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ Yang et al. 2022] |
− | + | |2018-2020 | |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |[[#Nedaplatin_.26_RT|Nedaplatin & RT]] | |
− | + | | style="background-color:#d73027" |Inferior PFS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[https://doi.org/10. | + | |[https://doi.org/10.1016/s0140-6736(24)00317-9 Lorusson et al. 2024 (KEYNOTE-A18)] |
− | | | + | |2020-06-09 to 2022-12-15 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Cisplatin.2C_Pembrolizumab.2C_RT|Cisplatin, Pembrolizumab, RT]] |
− | | style="background-color:# | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br> | ||
+ | ''Note: In GOG 120, this regimen was intended for disease.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 | + | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given 1 to 4 hours prior to radiation''' |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following study-specific criteria: |
− | + | **GOG 120, stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy | |
− | ''' | + | **GOG 219: 180 cGy x 23 to 25 fractions, for an initial dose of 41.4 to 4500 cGy |
+ | **Pearcey et al. 2002 & Zuliani et al. 2014: 180 cGy x 25 fractions, for an initial dose of 4500 cGy | ||
+ | **B9E-MC-JHQS & Sehouli et al. 2012: 180 cGy x 28 fractions, for an initial dose of 5040 cGy | ||
+ | **GOG 120, stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy | ||
+ | **Yang et al. 2022: 180 cGy/fraction/day, 5 days/week, a total of 25-28 fractions | ||
+ | '''6-week course, followed in 1 to 3 weeks by:''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Sequential [[#Brachytherapy_protocol|brachytherapy]] |
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #4, weekly cisplatin x 6, capped {{#subobject:ff6bdc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199904153401503 Keys et al. 1999 (GOG 123)] |
− | | | + | |1992-1997 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |RT | + | |[[Cervical_cancer_-_historical#Radiation_therapy|RT]] |
− | | style="background-color:# | + | |style="background-color:#1a9850"|Superior OS (co-primary endpoint)<br>OS36: 83% vs 74%<br>(RR 0.54, 95% CI 0.34-0.86) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2004.00.0497 Lanciano et al. 2005 (GOG 165)] |
− | | | + | |1997-2000 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
− | |[[# | + | |[[#Fluorouracil_.26_RT|Fluorouracil & RT]] |
− | | style="background-color:# | + | |style="background-color:#d9ef8b"|Might have superior ORR (secondary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> | + | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> (maximum dose of 70 mg) IV once per day on days 1, 8, 15, 22, 29, 36, '''given 4 hours before radiation''' |
− | + | ====Radiotherapy==== | |
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 | |
− | + | **Total number of fractions: 25 | |
− | + | **Total dose: 4500 cGy | |
− | + | '''6-week course, followed by:''' | |
− | ''' | + | </div> |
− | ====Radiotherapy | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: | + | ====Subsequent treatment==== |
− | + | *GOG 123: Sequential [[#Brachytherapy_protocol|brachytherapy]], then adjuvant [[Surgery#Hysterectomy|hysterectomy]] | |
− | ''' | + | *GOG 165: Sequential [[#Brachytherapy_protocol|brachytherapy]] |
− | + | </div></div><br> | |
− | ==== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | * | + | ===Regimen variant #5, q3wk cisplatin x 3 {{#subobject:9a0b6f|Variant=1}}=== |
− | |||
− | ===Regimen variant # | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10. | + | |[https://doi.org/10.1016/j.ijrobp.2011.05.002 Ryu et al. 2011 (KCCH GY 1005)] |
|2002-2004 | |2002-2004 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
− | |[[# | + | |[[#Cisplatin_.26_RT|Cisplatin & RT]]; weekly cisplatin |
− | |style="background-color:# | + | |style="background-color:#1a9850"|Superior OS60<br>OS60: 89% vs 66.5%<br>(HR 0.375, 95% CI 0.15-0.91) |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once per day on days 1, 22, 43 |
− | ==== | + | ====Radiotherapy==== |
− | * | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 1.8 to 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, (35 to 37) |
− | + | **Total number of fractions: 25 to 28 | |
− | ''' | + | **Total dose: 5000 cGy |
− | + | '''9-week course''' | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
+ | ====Subsequent treatment==== | ||
+ | *Sequential [[#Brachytherapy_protocol|brachytherapy]] (see paper for details) | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed] | ||
+ | ## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed] | ||
+ | # '''GOG 123:''' Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. [https://doi.org/10.1056/NEJM199904153401503 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202166/ PubMed] | ||
+ | # '''NCIC-CTG:''' Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. [https://doi.org/10.1200/JCO.2002.20.4.966 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11844818/ PubMed] | ||
+ | # '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078] | ||
+ | <!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. --> | ||
+ | # '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100] | ||
+ | # '''KCCH GY 1005:''' Ryu SY, Lee WM, Kim K, Park SI, Kim BJ, Kim MH, Choi SC, Cho CK, Nam BH, Lee ED. Randomized clinical trial of weekly vs triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e577-81. Epub 2011 Aug 11. [https://doi.org/10.1016/j.ijrobp.2011.05.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21840137/ PubMed] [https://clinicaltrials.gov/study/NCT01097252 NCT01097252] | ||
+ | # Sehouli J, Runnebaum IB, Fotopoulou C, Blohmer U, Belau A, Leber H, Hanker LC, Hartmann W, Richter R, Keyver-Paik MD, Oberhoff C, Heinrich G, du Bois A, Olbrich C, Simon E, Friese K, Kimmig R, Boehmer D, Lichtenegger W, Kuemmel S; NOGGO; AGO. A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Ann Oncol. 2012 Sep;23(9):2259-64. Epub 2012 Feb 21. [https://doi.org/10.1093/annonc/mdr628 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22357252/ PubMed] | ||
+ | # '''GOG 219:''' DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. Epub 2014 Jan 6. [https://doi.org/10.1200/JCO.2013.51.4265 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912330/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24395863/ PubMed] [https://clinicaltrials.gov/study/NCT00262821 NCT00262821] | ||
+ | #Zuliani AC, Esteves SC, Teixeira LC, Teixeira JC, de Souza GA, Sarian LO. Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized controlled trial. J Clin Oncol. 2014 Feb 20;32(6):542-7. Epub 2014 Jan 21. [https://doi.org/10.1200/jco.2013.50.1205 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24449243/ PubMed] | ||
+ | ##'''Update:''' Fachini AMD, Zuliani AC, Sarian LO, Teixeira JC, Esteves SCB, da Costa Machado H, Zeferino LC. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial. Gynecol Oncol. 2021 Feb;160(2):379-383. Epub 2020 Dec 16. [https://doi.org/10.1016/j.ygyno.2020.11.029 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33341239/ PubMed] | ||
+ | # '''RADCHOC:''' Lutgens LC, Koper PC, Jobsen JJ, van der Steen-Banasik EM, Creutzberg CL, van den Berg HA, Ottevanger PB, van Rhoon GC, van Doorn HC, Houben R, van der Zee J. Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial. Radiother Oncol. 2016 Sep;120(3):378-382. Epub 2016 Feb 17. [https://doi.org/10.1016/j.radonc.2016.02.010 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26897513/ PubMed] | ||
+ | # '''CRACx:''' Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: a randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. [https://doi.org/10.1001/jamaoncol.2017.5179 link to original article] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29423520/ PubMed] [https://clinicaltrials.gov/study/NCT00193791 NCT00193791] | ||
+ | #Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. [https://doi.org/10.1016/j.esmoop.2022.100565 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35994789/ PubMed] ChiCTR1800017108 | ||
+ | #'''EORTC-55994:''' Kenter GG, Greggi S, Vergote I, Katsaros D, Kobierski J, van Doorn H, Landoni F, van der Velden J, Reed N, Coens C, van Luijk I, Colombo N, Steen-Banasik EV, Ottevanger N, Casado A; EORTC-55994 Study Group. Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994. J Clin Oncol. 2023 Nov 10;41(32):5035-5043. Epub 2023 Sep 1. [https://doi.org/10.1200/jco.22.02852 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37656948/ PubMed] [https://clinicaltrials.gov/study/NCT00039338 NCT00039338] | ||
+ | # '''CALLA:''' Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. [https://doi.org/10.1016/s1470-2045(23)00479-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38039991/ PubMed] [https://clinicaltrials.gov/study/NCT03830866 NCT03830866] | ||
+ | #'''KEYNOTE-A18:''' Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. [https://doi.org/10.1016/s0140-6736(24)00317-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38521086/ PubMed] [https://clinicaltrials.gov/study/NCT04221945 NCT04221945] | ||
+ | #'''NRG-GY006:''' [https://clinicaltrials.gov/study/NCT02466971 NCT02466971] | ||
− | === | + | ==Cisplatin, Pembrolizumab, RT {{#subobject:8pec49|Regimen=1}}== |
+ | Cisplatin, Pembrolizumab, RT: Cisplatin, Pembrolizumab, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:f6gc1c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1016/s0140-6736(24)00317-9 Lorusson et al. 2024 (KEYNOTE-A18)] | |
− | | | + | |2020-06-09 to 2022-12-15 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
− | | | + | |[[#Cisplatin_.26_RT|Cisplatin & RT]] |
− | |style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>PFS24: 68% vs 57%<br>(HR 0.70, 95% CI 0.55-0.89)<br><br>Did not meet co-primary endpoint of OS |
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV | + | *[[Cisplatin (Platinol)]] as follows: |
− | ====Radiotherapy | + | **Cycles 1 & 2: 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | ====Radiotherapy==== |
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | |
− | + | ====Immunotherapy==== | |
− | + | *[[Pembrolizumab (Keytruda)]] as follows: | |
− | ==== | + | **Cycles 1 to 5: 200 mg IV once on day 1 |
− | * | + | **Cycles 6 to 20: 400 mg IV once on day 1 |
− | ** | + | '''21-day cycle for 5 cycles, then 42-day cycle for 15 cycles''' |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # ''' | + | #'''KEYNOTE-A18:''' Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. [https://doi.org/10.1016/s0140-6736(24)00317-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38521086/ PubMed] [https://clinicaltrials.gov/study/NCT04221945 NCT04221945] |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ==Cisplatin | + | ==Cisplatin & Fluorouracil (CF) & RT {{#subobject:7fff9b|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
CF & RT: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CF & RT: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 70/4000 x 4 {{#subobject:749e5d|Variant=1}}=== | ===Regimen variant #1, 70/4000 x 4 {{#subobject:749e5d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 334: | Line 431: | ||
|[https://doi.org/10.1200/jco.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)] | |[https://doi.org/10.1200/jco.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)] | ||
|1986-1990 | |1986-1990 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Hydroxyurea_.26_RT|Hydroxyurea & RT]] | |[[#Hydroxyurea_.26_RT|Hydroxyurea & RT]] | ||
− | |style="background-color:#91cf60"|Seems to have superior OS | + | |style="background-color:#91cf60"|Seems to have superior OS (co-primary endpoint)<br>Median OS: NYR vs 59.8 mo<br>(RR 0.74, 90% CI 0.58-0.95) |
|- | |- | ||
|[https://doi.org/10.1200/jco.2000.18.8.1606 Peters et al. 2000 (GOG 109/SWOG-8797)] | |[https://doi.org/10.1200/jco.2000.18.8.1606 Peters et al. 2000 (GOG 109/SWOG-8797)] | ||
|1991-1996 | |1991-1996 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[#Radiation_therapy|Radiation therapy]] | + | |[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]] |
− | |style="background-color:#1a9850"|Superior OS | + | |style="background-color:#1a9850"|Superior OS (co-primary endpoint)<br>OS48: 81% vs 71%<br>(HR 0.51) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV over 2 hours once on | + | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 22, 43, 64 |
− | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on | + | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1, 22, 43, 64 (total dose: 16,000 mg/m<sup>2</sup>) |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 170 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 39 (29 fractions, for a total dose of 4930 cGy) |
− | **Patients with positive high common iliac lymph nodes also received | + | **Patients with positive high common iliac lymph nodes also received 150 cGy x 30 fractions, for a total dose of 4500 cGy |
− | ''' | + | '''12-week course''' |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 75/4000 x 3 {{#subobject:16dd3c|Variant=1}}=== | ===Regimen variant #2, 75/4000 x 3 {{#subobject:16dd3c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199904153401501 Morris et al. 1999 (RTOG 9001)] |
|1990-1997 | |1990-1997 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[#Radiation_therapy|Radiation therapy]] | + | |[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]] |
− | |style="background-color:#1a9850"|Superior OS | + | |style="background-color:#1a9850"|Superior OS (primary endpoint)<br>OS60: 73% vs 58% |
|- | |- | ||
|} | |} | ||
+ | ''Note: radiation could start one day before chemotherapy, on "day 0".'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on | + | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 22, 43, '''given first''' |
− | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on | + | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1, 22, 43 (total dose: 12,000 mg/m<sup>2</sup>) |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy) |
− | ''' | + | '''9-week course''' |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *Brachytherapy (see paper for details) | + | *[[#Brachytherapy_protocol|Brachytherapy]] (see paper for details) |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. [https:// | + | # '''RTOG 9001:''' Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. [https://doi.org/10.1056/NEJM199904153401501 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202164/ PubMed] |
− | # '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517 PubMed] | + | # '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517/ PubMed] |
− | # '''GOG 109/SWOG-8797:''' Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [https://doi.org/10.1200/jco.2000.18.8.1606 link to original article] '''contains | + | # '''GOG 109/SWOG-8797:''' Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. [https://doi.org/10.1200/jco.2000.18.8.1606 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10764420/ PubMed] |
− | + | ==Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT {{#subobject:670a50|Regimen=1}}== | |
− | ==Cisplatin | ||
− | |||
− | |||
− | |||
− | |||
− | |||
Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | + | <div class="toccolours" style="background-color:#c8a2c8"> | |
− | == | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1056/NEJM199904153401502 Rose et al. 1999 (GOG 120)] |
|rowspan=2|1992-1997 | |rowspan=2|1992-1997 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
|1. [[#Cisplatin_.26_RT|Cisplatin & RT]] | |1. [[#Cisplatin_.26_RT|Cisplatin & RT]] | ||
− | |style="background-color:#ffffbf"|Did not meet primary endpoints of PFS/OS | + | |style="background-color:#ffffbf"|Did not meet co-primary endpoints of PFS/OS |
|- | |- | ||
|2. [[#Hydroxyurea_.26_RT|Hydroxyurea & RT]] | |2. [[#Hydroxyurea_.26_RT|Hydroxyurea & RT]] | ||
− | |style="background-color:#1a9850"|Superior OS | + | |style="background-color:#1a9850"|Superior OS (co-primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive therapy {{#subobject:bc5f6d|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on | + | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 29 |
− | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on | + | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose per cycle: 4000 mg/m<sup>2</sup>) |
*[[Hydroxyurea (Hydrea)]] 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation on weeks 1 to 6''' | *[[Hydroxyurea (Hydrea)]] 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation on weeks 1 to 6''' | ||
− | + | ====Radiotherapy==== | |
− | ====Radiotherapy | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following stage-based criteria: |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | **Stage IIB: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 25 (24 fractions, for an initial dose of 4080 cGy) |
− | **Stage IIB | + | **Stage III or IVA: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (30 fractions, for an initial dose of 5100 cGy) |
− | **Stage III or IVA | ||
'''5- to 6-week course, followed by:''' | '''5- to 6-week course, followed by:''' | ||
− | + | </div></div><br> | |
− | ====Radiotherapy | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | *Stage IIB patients received | + | ===Consolidation=== |
− | *Stage III or IVA disease received | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | **Patients that could not receive brachytherapy underwent additional [[External_beam_radiotherapy|external beam radiation therapy]] for a total dose of | + | ====Radiotherapy==== |
+ | *Stage IIB patients received 4000 cGy by [[Brachytherapy|intracavitary brachytherapy]], for a total dose of 8080 cGy to point A | ||
+ | *Stage III or IVA disease received 3000 cGy by [[Brachytherapy|intracavitary brachytherapy]], for a total dose of 8100 cGy to point A | ||
+ | **Patients that could not receive brachytherapy underwent additional [[External_beam_radiotherapy|external beam radiation therapy]] for a total dose of 6120 cGy | ||
+ | '''One course''' | ||
+ | </div></div></div> | ||
===References=== | ===References=== | ||
− | # '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https:// | + | # '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed] |
− | ## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627 PubMed] | + | ## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed] |
− | + | ==Cisplatin & Gemcitabine (GC) & RT {{#subobject:8df5df|Regimen=1}}== | |
− | ==Cisplatin | ||
− | |||
− | |||
− | |||
− | |||
− | |||
Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:342f7f|Variant=1}}=== | ===Regimen {{#subobject:342f7f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 446: | Line 543: | ||
|[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)] | |[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)] | ||
|2002-2004 | |2002-2004 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Cisplatin_.26_RT|Cisplatin & RT]] | |[[#Cisplatin_.26_RT|Cisplatin & RT]] | ||
− | |style="background-color:#91cf60"|Seems to have superior OS | + | |style="background-color:#91cf60"|Seems to have superior PFS (primary endpoint)<br>PFS36: 74.4% vs 65%<br>(HR 0.68, 95% CI 0.49-0.95)<br><br>Seems to have superior OS (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.68, 95% CI 0.49-0.95) |
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdt142 Cetina et al. 2013] | |[https://doi.org/10.1093/annonc/mdt142 Cetina et al. 2013] | ||
|2004-2009 | |2004-2009 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given first, 1 to 2 hours before radiation''' | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given first, 1 to 2 hours before radiation''' | ||
*[[Gemcitabine (Gemzar)]] 125 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 to 2 hours before radiation''' | *[[Gemcitabine (Gemzar)]] 125 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 to 2 hours before radiation''' | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for an initial dose of 5040 cGy) |
− | |||
'''6-week course''' | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *B9E-MC-JHQS: [[# | + | *B9E-MC-JHQS: [[#Brachytherapy_protocol|Brachytherapy]] (30 to 3500 cGy delivered to point A), then adjuvant [[#Cisplatin_.26_Gemcitabine_.28GC.29|GC]], in 2 weeks |
− | *Cetina et al. 2013: [[# | + | *Cetina et al. 2013: [[#Brachytherapy_protocol|Brachytherapy]] verus [[Surgery#Radical_hysterectomy|radical hysterectomy]] |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | <!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. NCT00191100), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. --> | + | <!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. --> |
− | # '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains | + | # '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100] |
− | # Cetina L, González-Enciso A, Cantú D, Coronel J, Pérez-Montiel D, Hinojosa J, Serrano A, Rivera L, Poitevin A, Mota A, Trejo E, Montalvo G, Muñoz D, Robles-Flores J, de la Garza J, Chanona J, Jiménez-Lima R, Wegman T, Dueñas-González A. Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients. Ann Oncol. 2013 Aug;24(8):2043-7. Epub 2013 Apr 21. [https://doi.org/10.1093/annonc/mdt142 link to original article] '''contains | + | # Cetina L, González-Enciso A, Cantú D, Coronel J, Pérez-Montiel D, Hinojosa J, Serrano A, Rivera L, Poitevin A, Mota A, Trejo E, Montalvo G, Muñoz D, Robles-Flores J, de la Garza J, Chanona J, Jiménez-Lima R, Wegman T, Dueñas-González A. Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients. Ann Oncol. 2013 Aug;24(8):2043-7. Epub 2013 Apr 21. [https://doi.org/10.1093/annonc/mdt142 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23609186/ PubMed] |
− | |||
==Fluorouracil & RT {{#subobject:e9a589|Regimen=1}}== | ==Fluorouracil & RT {{#subobject:e9a589|Regimen=1}}== | ||
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5-FU & RT: '''<u>5-F</u>'''luouro'''<u>U</u>'''racil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | 5-FU & RT: '''<u>5-F</u>'''luouro'''<u>U</u>'''racil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | + | <div class="toccolours" style="background-color:#c8a2c8"> | |
− | == | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 491: | Line 584: | ||
|[https://doi.org/10.1200/jco.2004.00.0497 Lanciano et al. 2005 (GOG 165)] | |[https://doi.org/10.1200/jco.2004.00.0497 Lanciano et al. 2005 (GOG 165)] | ||
|1997-2000 | |1997-2000 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Cisplatin_.26_RT|Cisplatin & RT]] | |[[#Cisplatin_.26_RT|Cisplatin & RT]] | ||
− | |style="background-color:#fee08b"|Might have inferior ORR | + | |style="background-color:#fee08b"|Might have inferior ORR (secondary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive therapy {{#subobject:38087d|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on | + | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29, 36 (total dose: 6750 mg/m<sup>2</sup>) |
− | + | ====Radiotherapy==== | |
− | ====Radiotherapy | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for an initial dose of 4080 cGy) |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''6-week course, followed by:''' | '''6-week course, followed by:''' | ||
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Consolidation=== | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
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====Radiotherapy==== | ====Radiotherapy==== | ||
− | * | + | **EITHER Low-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 4000 cGy to point A given in 1 to 2 fractions |
− | + | **OR High-dose rate [[Brachytherapy|intracavitary brachytherapy]] of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT | |
+ | *Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete | ||
+ | </div></div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''GOG 165:''' Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. [https://doi.org/10.1200/jco.2004.00.0497 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16230678/ PubMed] [https://clinicaltrials.gov/study/NCT00003078 NCT00003078] |
− | |||
==Hydroxyurea & RT {{#subobject:b93f37|Regimen=1}}== | ==Hydroxyurea & RT {{#subobject:b93f37|Regimen=1}}== | ||
− | |||
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Hydroxyurea & RT: Hydroxyurea & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Hydroxyurea & RT: Hydroxyurea & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | + | <div class="toccolours" style="background-color:#c8a2c8"> | |
− | == | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0360-3016(79)91209-4 Hreshchyshyn et al. 1979 (GOG 04)] |
|1970-1976 | |1970-1976 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[#Radiation_therapy|Radiation therapy]] | + | |[[Cervical_cancer_-_historical#Radiation_therapy|Radiation therapy]] |
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/0002-9378(88)90499-1 Stehman et al. 1988 (GOG 56)] | ||
+ | |1981-06 to 1985-12 | ||
+ | |style="background-color:#1a9851"|Randomized | ||
+ | |[[#Misonidazole_.26_RT_999|Misonidazole & RT]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)] | |[https://doi.org/10.1200/jco.1999.17.5.1339 Whitney et al. 1999 (GOG 85/SWOG 8695)] | ||
|1986-1990 | |1986-1990 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT|Cisplatin, Fluorouracil, RT]] |
|style="background-color:#fc8d59"|Seems to have inferior OS | |style="background-color:#fc8d59"|Seems to have inferior OS | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1056/NEJM199904153401502 Rose et al. 1999 (GOG 120)] |
|rowspan=2|1992-1997 | |rowspan=2|1992-1997 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
|1. [[#Cisplatin_.26_RT|Cisplatin & RT]] | |1. [[#Cisplatin_.26_RT|Cisplatin & RT]] | ||
|style="background-color:#d73027"|Inferior OS | |style="background-color:#d73027"|Inferior OS | ||
|- | |- | ||
− | |2. [[# | + | |2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Hydroxyurea.2C_RT|Cisplatin, Fluorouracil, Hydroxyurea, RT]] |
|style="background-color:#d73027"|Inferior OS | |style="background-color:#d73027"|Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy for GOG 56 is based on the 1993 update.'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive therapy {{#subobject:176533|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Hydroxyurea (Hydrea)]] 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation | + | *[[Hydroxyurea (Hydrea)]] as follows: |
− | ====Radiotherapy | + | **Weeks 1 to 6: 2000 mg/m<sup>2</sup> PO two times per week, '''given 2 hours before radiation''' |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | ====Radiotherapy==== |
− | **Stage IIB | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] by the following stage-based criteria: |
− | **Stage III or IVA | + | **Stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy |
− | + | **Stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy | |
− | ''' | + | '''7- to 9-week course''' |
− | + | </div></div><br> | |
− | ====Radiotherapy | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | * | + | ===Consolidation=== |
− | *Stage III or IVA | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Radiotherapy==== | |
− | + | *[[Brachytherapy|Intracavitary brachytherapy]] by the following stage-based criteria: | |
+ | **Stage IIB: 4000 cGy for a total dose of 8080 cGy to point A | ||
+ | *Stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A | ||
+ | *Patients that could not receive brachytherapy underwent additional [[External_beam_radiotherapy|external beam radiation therapy]] for a total dose of 6120 cGy | ||
+ | </div></div></div> | ||
===References=== | ===References=== | ||
− | # Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA. Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys. 1979 Mar;5(3):317-22. [ | + | # Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA. Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys. 1979 Mar;5(3):317-22. [https://doi.org/10.1016/0360-3016(79)91209-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/110744/ PubMed] |
− | # '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https:// | + | # '''GOG 56:''' Stehman FB, Bundy BN, Keys H, Currie JL, Mortel R, Creasman WT. A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix: A preliminary report of a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1988 Jul;159(1):87-94. [https://doi.org/10.1016/0002-9378(88)90499-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3293456/ PubMed] |
− | ## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627 PubMed] | + | ##'''Update:''' Stehman FB, Bundy BN, Thomas G, Keys HM, d'Ablaing G 3rd, Fowler WC Jr, Mortel R, Creasman WT. Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial. J Clin Oncol. 1993 Aug;11(8):1523-8. [https://doi.org/10.1200/jco.1993.11.8.1523 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8336190/ PubMed] |
− | # '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517 PubMed] | + | # '''GOG 120:''' Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. [https://doi.org/10.1056/NEJM199904153401502 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10202165/ PubMed] |
+ | ## '''Update:''' Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. [https://doi.org/10.1200/jco.2006.09.4532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17502627/ PubMed] | ||
+ | # '''GOG 85/SWOG 8695:''' Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. [https://doi.org/10.1200/jco.1999.17.5.1339 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334517/ PubMed] | ||
− | == | + | ==Nedaplatin & RT {{#subobject:igjz49|Regimen=1}}== |
− | + | Nedaplatin & RT: Nedaplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:638icz|Variant=1}}=== | |
− | |||
− | ===Regimen {{#subobject: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ Yang et al. 2022] | |
− | + | |2018-2020 | |
− | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |
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− | |[https://www. | ||
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− | |style="background-color:#1a9851"|Phase | ||
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|[[#Cisplatin_.26_RT|Cisplatin & RT]] | |[[#Cisplatin_.26_RT|Cisplatin & RT]] | ||
− | |style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS36 (primary endpoint)<br>Median PFS: 30 vs 28 mo<br>(HR 0.25, 95% CI 0.08-0.77) |
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|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Chemotherapy==== | ||
+ | *[[Nedaplatin (Aqupla)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, +/- 36 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[ | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day, 5 days/week, a total of 25-28 fractions |
− | + | </div></div> | |
− | |||
− | |||
===References=== | ===References=== | ||
− | # | + | #Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. [https://doi.org/10.1016/j.esmoop.2022.100565 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9588898/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35994789/ PubMed] ChiCTR1800017108 |
− | |||
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− | |||
− | |||
− | |||
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=Adjuvant therapy= | =Adjuvant therapy= | ||
==Carboplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}== | ==Carboplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:93caff|Variant=1}}=== | ===Regimen {{#subobject:93caff|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 712: | Line 716: | ||
|[https://doi.org/10.1200/JCO.2010.30.4899 Blohmer et al. 2011 (NOGGO-AGO)] | |[https://doi.org/10.1200/JCO.2010.30.4899 Blohmer et al. 2011 (NOGGO-AGO)] | ||
|1999-2001 | |1999-2001 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Complex_multipart_regimens#NOGGO-AGO|See link]] | |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | ||
| style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | | style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | ||
|- | |- | ||
|} | |} | ||
− | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[Surgery#Radical_hysterectomy|Wertheim-Meigs radical abdominal hysterectomy]] | *[[Surgery#Radical_hysterectomy|Wertheim-Meigs radical abdominal hysterectomy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 4 IV over 60 minutes once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 4 IV over 60 minutes once on day 1 | ||
− | *[[Ifosfamide (Ifex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3 | + | *[[Ifosfamide (Ifex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3, with mesa |
− | ====Supportive | + | ====Supportive therapy==== |
− | *[[Mesna (Mesnex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3, with | + | *[[Mesna (Mesnex)]] 1600 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 3, with ifosfamide |
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Radiation_therapy_2|Pelvic EBRT]] x | + | *[[Cervical_cancer_-_historical#Radiation_therapy_2|Pelvic EBRT]] x 5040 cGy |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains | + | # '''NOGGO-AGO:''' Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed] |
− | |||
==Cisplatin & Gemcitabine (GC) {{#subobject:5de31f|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) {{#subobject:5de31f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:c4c8f2|Variant=1}}=== | ===Regimen {{#subobject:c4c8f2|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)] | |[https://doi.org/10.1200/jco.2009.25.9663 Dueñas-González et al. 2011 (B9E-MC-JHQS)] | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |2002-2004 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *Definitive [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_RT|Cisplatin, Gemcitabine, RT]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | <!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. NCT00191100), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. --> | + | <!-- Presented in part on the clinical trial registry located at ClinicalTrials.gov (identification No. [https://clinicaltrials.gov/study/NCT00191100 NCT00191100]), on the Lilly Clinical Trial Registry (www.lillytrials.com: trial identification No. 4015), and at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. --> |
− | # '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains | + | # '''B9E-MC-JHQS:''' Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2009.25.9663 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21444871/ PubMed] [https://clinicaltrials.gov/study/NCT00191100 NCT00191100] |
− | |||
==Radiation therapy {{#subobject:e34211|Regimen=1}}== | ==Radiation therapy {{#subobject:e34211|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:aa4d8e|Variant=1}}=== | ===Regimen {{#subobject:aa4d8e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/JCO.2010.30.4899 Blohmer et al. 2011] | + | |[https://doi.org/10.1200/JCO.2010.30.4899 Blohmer et al. 2011 (NOGGO-AGO)] |
|1999-2001 | |1999-2001 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Complex_multipart_regimens#NOGGO-AGO|See link]] | |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | ||
| style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | | style="background-color:#fee08b" |[[Complex_multipart_regimens#NOGGO-AGO|See link]] | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery#Cervical_cancer_surgery|Surgery]], then [[#Carboplatin_.26_Ifosfamide|Carboplatin & Ifosfamide]] x 4 | + | *[[Surgery#Cervical_cancer_surgery|Surgery]], then adjuvant [[#Carboplatin_.26_Ifosfamide|Carboplatin & Ifosfamide]] x 4 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External beam radiotherapy]]: | + | *[[External beam radiotherapy]]: 180 cGy for 28 fractions, for a total dose of 5040 cGy |
*If resection margins positive, patients received one of the following: | *If resection margins positive, patients received one of the following: | ||
− | **EBRT boost of 2 x | + | **EBRT boost of 2 x 500 cGy |
− | **Low-dose | + | **Low-dose brachytherapy |
− | |||
'''6-week course''' | '''6-week course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains | + | # '''NOGGO-AGO:''' Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed] |
=Persistent, recurrent, or metastatic disease, first-line therapy= | =Persistent, recurrent, or metastatic disease, first-line therapy= | ||
+ | ==ABCP {{#subobject:bcc235|Regimen=1}}== | ||
+ | ABCP: '''<u>A</u>'''tezolizumab, '''<u>B</u>'''evacizumab, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:76uty4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)] | ||
+ | |2018-10-08 to 2021-08-20 | ||
+ | |style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 32.1 vs 22.8 mo<br>(HR 0.68, 95% CI 0.52-0.88)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 13.7 vs 10.4 mo<br>(HR 0.62, 95% CI 0.49-0.78) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839] | ||
==Carboplatin monotherapy {{#subobject:fae1e7|Regimen=1}}== | ==Carboplatin monotherapy {{#subobject:fae1e7|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:fe1b36|Variant=1}}=== | ===Regimen {{#subobject:fe1b36|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0090-8258(90)90262-j Weiss et al. 1990] |
− | |style="background-color:#91cf61"|Phase | + | |NR |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV once on day 1 | *[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS; [[Study_Groups#SWOG|SWOG]]. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. [ | + | # Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS; [[Study_Groups#SWOG|SWOG]]. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. [https://doi.org/10.1016/0090-8258(90)90262-j link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2258080/ PubMed] |
==Carboplatin & Docetaxel {{#subobject:39c86d|Regimen=1}}== | ==Carboplatin & Docetaxel {{#subobject:39c86d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 6 cycles {{#subobject:9fb5d5|Variant=1}}=== | ===Regimen variant #1, 6 cycles {{#subobject:9fb5d5|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/IGC.0b013e3181a81221 Takekida et al. 2010] |
− | |style="background-color:#91cf61"|Phase | + | |2004-01 to 2005-12 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second''' | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second''' | ||
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Dexamethasone (Decadron)]] | *[[Dexamethasone (Decadron)]] | ||
*[[Ondansetron (Zofran)]] or [[Granisetron]] | *[[Ondansetron (Zofran)]] or [[Granisetron]] | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia | *[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, indefinite {{#subobject:9ce265|Variant=1}}=== | ===Regimen variant #2, indefinite {{#subobject:9ce265|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2004.11.044 Nagao et al. 2005] |
− | |style="background-color:#ffffbe"|Pilot, | + | |2001-2004 |
+ | |style="background-color:#ffffbe"|Pilot, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second''' | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given second''' | ||
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Dexamethasone (Decadron)]] | *[[Dexamethasone (Decadron)]] | ||
*[[Ondansetron (Zofran)]] or [[Granisetron]] | *[[Ondansetron (Zofran)]] or [[Granisetron]] | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia | *[[Filgrastim (Neupogen)]] 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer: a pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [ | + | # Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer: a pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. [https://doi.org/10.1016/j.ygyno.2004.11.044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15721429/ PubMed] |
− | # Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. [https:// | + | # Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. [https://doi.org/10.1111/IGC.0b013e3181a81221 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21370599/ PubMed] |
− | |||
==Carboplatin & Paclitaxel (CP) {{#subobject:be30d5|Regimen=1}}== | ==Carboplatin & Paclitaxel (CP) {{#subobject:be30d5|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin | TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:7668ec|Variant=1}}=== | ===Regimen {{#subobject:7668ec|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/igc.0b013e3181a40a8b Pectasides et al. 2009a] |
|NR | |NR | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 885: | Line 920: | ||
|[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)] | |[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)] | ||
|2006-2009 | |2006-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
− | |style="background-color:#eeee01"|Non-inferior OS | + | |style="background-color:#eeee01"|Non-inferior OS (primary endpoint)<br>Median OS: 17.5 vs 18.3 mo<br>(HR 0.994, 90% CI 0.79-1.25) |
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Pectasides et al. 2009a allowed the regimen to be given up to 9 cycles.'' | + | ''Note: Pectasides et al. 2009a allowed the regimen to be given up to 9 cycles. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second''' | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second''' | ||
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first''' | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first''' | ||
+ | '''21-day cycle for 6 or more cycles (see note)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. [https://doi.org/10.1111/igc.0b013e3181a40a8b link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19509587/ PubMed] | ||
+ | # '''JCOG0505:''' Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.58.4391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732161/ PubMed] [https://clinicaltrials.gov/study/NCT00295789 NCT00295789] | ||
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
− | '''21-day | + | ==Carboplatin & Paclitaxel (CP) & Bevacizumab {{#subobject:be3165|Regimen=1}}== |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:76615h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)] | ||
+ | |2018-10-08 to 2021-08-20 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#ABCP|ABCP]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Atezolizumab.2C_Bevacizumab|Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS/OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: In KEYNOTE-826, the decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): AUC 5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
+ | #'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839] | ||
+ | ==Carboplatin & Paclitaxel (CP), Bevacizumab, Pembrolizumab {{#subobject:yh2n65|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ug81uh|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br> | ||
+ | ''Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): AUC 5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Pembrolizumab (Keytruda)]] as follows: | ||
+ | **Cycles 1 up to 35: 200 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] |
− | # ''' | + | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] |
− | + | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | |
− | == | + | ==Carboplatin & Paclitaxel (CP) & Pembrolizumab {{#subobject:ch10d5|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:ag7nec|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br> | ||
+ | ''Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): AUC 5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
+ | '''21-day cycle for up to 35 cycles (2 years)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
+ | ==Cisplatin monotherapy {{#subobject:117c0b|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a3542f|Variant=1}}=== | ===Regimen {{#subobject:a3542f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 916: | Line 1,074: | ||
|[https://pubmed.ncbi.nlm.nih.gov/498154 Thigpen et al. 1979a] | |[https://pubmed.ncbi.nlm.nih.gov/498154 Thigpen et al. 1979a] | ||
|NR in abstract | |NR in abstract | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 922: | Line 1,080: | ||
|[https://doi.org/10.1200/JCO.1985.3.8.1079 Bonomi et al. 1985 (GOG 43)] | |[https://doi.org/10.1200/JCO.1985.3.8.1079 Bonomi et al. 1985 (GOG 43)] | ||
|1978-1982 | |1978-1982 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |1. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose<br> 2. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose, split doses | + | |1. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose<br>2. [[#Cisplatin_monotherapy|Cisplatin]]; higher dose, split doses |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0090-8258(89)80033-2 Thigpen et al. 1989 (GOG 64)] |
|1982-1985 | |1982-1985 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Cisplatin_monotherapy|Cisplatin]]; CI | |[[#Cisplatin_monotherapy|Cisplatin]]; CI | ||
| style="background-color:#ffffbf" |Did not meet primary efficacy endpoints | | style="background-color:#ffffbf" |Did not meet primary efficacy endpoints | ||
Line 934: | Line 1,092: | ||
|rowspan=2|[https://doi.org/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)] | |rowspan=2|[https://doi.org/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)] | ||
|rowspan=2|1990-1994 | |rowspan=2|1990-1994 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
− | |[[#Cisplatin_.26_Ifosfamide|Cisplatin & Ifosfamide]] | + | |1. [[#Cisplatin_.26_Ifosfamide|Cisplatin & Ifosfamide]] |
|style="background-color:#d73027"|Inferior PFS | |style="background-color:#d73027"|Inferior PFS | ||
|- | |- | ||
− | |Cisplatin & Mitolactol | + | |2. [[#Cisplatin_.26_Mitolactol_999|Cisplatin & Mitolactol]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
|[https://doi.org/10.1023/a:1011165115426 Vermorken et al. 2001] | |[https://doi.org/10.1023/a:1011165115426 Vermorken et al. 2001] | ||
|1986-1991 | |1986-1991 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |BEMP | + | |[[#BEMP_999|BEMP]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2004.04.170 Moore et al. 2004 (GOG 169)] | |[https://doi.org/10.1200/jco.2004.04.170 Moore et al. 2004 (GOG 169)] | ||
|1997-1999 | |1997-1999 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |[[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
|style="background-color:#d73027"|Inferior PFS | |style="background-color:#d73027"|Inferior PFS | ||
Line 955: | Line 1,113: | ||
|rowspan=2|[https://doi.org/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)] | |rowspan=2|[https://doi.org/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)] | ||
|rowspan=2|1999-2002 | |rowspan=2|1999-2002 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
|1. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | |1. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | ||
|style="background-color:#fc8d59"|Seems to have inferior OS | |style="background-color:#fc8d59"|Seems to have inferior OS | ||
|- | |- | ||
− | |2. MVAC | + | |2. [[#MVAC_999|MVAC]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6162273/ Aoki et al. 2018 (Taiho 10020380)] |
|2008-2011 | |2008-2011 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Cisplatin & S-1 | + | |[[#Cisplatin_.26_S-1_999|Cisplatin & S-1]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycles; if not responding, given for maximum of 6 cycles''' | '''21-day cycles; if not responding, given for maximum of 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J; Gynecologic Oncology Group. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1549-55. [https://pubmed.ncbi.nlm.nih.gov/498154 PubMed] | + | # Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J; Gynecologic Oncology Group. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1549-55. [https://pubmed.ncbi.nlm.nih.gov/498154/ PubMed] |
− | # '''GOG 43:''' Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. [https://doi.org/10.1200/JCO.1985.3.8.1079 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3894589 PubMed] | + | # '''GOG 43:''' Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. [https://doi.org/10.1200/JCO.1985.3.8.1079 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3894589/ PubMed] |
− | # '''GOG 64:''' Thigpen JT, Blessing JA, DiSaia PJ, Fowler WC Jr, Hatch KD. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1989 Feb;32(2):198-202. [https:// | + | # '''GOG 64:''' Thigpen JT, Blessing JA, DiSaia PJ, Fowler WC Jr, Hatch KD. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1989 Feb;32(2):198-202. [https://doi.org/10.1016/s0090-8258(89)80033-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2910782/ PubMed] |
− | # '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains | + | # '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8996138/ PubMed] |
− | # Vermorken JB, Zanetta G, | + | # Vermorken JB, Zanetta G, Freire de Oliveira C, van der Burg ME, Lacave AJ, Teodorovic I, Boes GH, Colombo N; [[Study_Groups#EORTC|EORTC]] Gynecological Cancer Cooperative Group. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol. 2001 Jul;12(7):967-74. [https://doi.org/10.1023/a:1011165115426 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11521804/ PubMed] |
− | # '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains | + | # '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284262/ PubMed] |
<!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. --> | <!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. --> | ||
− | # '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains | + | # '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15911865/ PubMed] [https://clinicaltrials.gov/study/NCT00003945 NCT00003945] |
− | # '''Taiho 10020380:''' Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, Katsumata N, Cha SD, Kim JH, Kim BG, Hirashima Y, Fujiwara K, Kim YT, Kim SM, Chung HH, Chang TC, Kamura T, Takizawa K, Takeuchi M, Kang SB. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer. 2018 Aug;119(5):530-537. Epub 2018 Aug 3. [https:// | + | # '''Taiho 10020380:''' Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, Katsumata N, Cha SD, Kim JH, Kim BG, Hirashima Y, Fujiwara K, Kim YT, Kim SM, Chung HH, Chang TC, Kamura T, Takizawa K, Takeuchi M, Kang SB. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer. 2018 Aug;119(5):530-537. Epub 2018 Aug 3. [https://doi.org/10.1038/s41416-018-0206-7 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6162273/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30072745/ PubMed] [https://clinicaltrials.gov/study/NCT00770874 NCT00770874] |
− | |||
==Cisplatin & Gemcitabine (GC) {{#subobject:fbbad7|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) {{#subobject:fbbad7|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin | GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:2e2004|Variant=1}}=== | ===Regimen {{#subobject:2e2004|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,002: | Line 1,156: | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | ||
|rowspan=3|2003-2007 | |rowspan=3|2003-2007 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
− | |style="background-color:#fc8d59"|Seems to have inferior PFS | + | |style="background-color:#fc8d59"|Seems to have inferior PFS (secondary endpoint) |
|- | |- | ||
|2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | |2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |3. [[#Cisplatin_. | + | |3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | ||
− | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains | + | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077] |
− | |||
==Cisplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}== | ==Cisplatin & Ifosfamide {{#subobject:3c6ded|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:93caff|Variant=1}}=== | ===Regimen {{#subobject:93caff|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,038: | Line 1,188: | ||
|rowspan=2 |[https://doi.org/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)] | |rowspan=2 |[https://doi.org/10.1200/jco.1997.15.1.165 Omura et al. 1997 (GOG 110)] | ||
|rowspan=2|1990-1994 | |rowspan=2|1990-1994 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[#Cisplatin_monotherapy|Cisplatin]] | + | |1. [[#Cisplatin_monotherapy|Cisplatin]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (secondary endpoint) |
|- | |- | ||
− | |Cisplatin & Mitolactol | + | |2. [[#Cisplatin_.26_Mitolactol_777|Cisplatin & Mitolactol]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2002.07.045 Bloss et al. 2002 (GOG 149)] | |[https://doi.org/10.1200/JCO.2002.07.045 Bloss et al. 2002 (GOG 149)] | ||
|1994-1997 | |1994-1997 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Stub#CIB|CIB]] | |[[Stub#CIB|CIB]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Ifosfamide (Ifex)]] | + | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 concurrent with mesna |
− | + | ====Supportive therapy==== | |
+ | *[[Mesna (Mesnex)]] 6000 mg/m<sup>2</sup> IV continuous infusion over 36 hours, started on day 1 concurrent with ifosfamide | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains | + | # '''GOG 110:''' Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. [https://doi.org/10.1200/jco.1997.15.1.165 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8996138/ PubMed] |
− | # '''GOG 149:''' Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, Markman M, Benda J. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2002 Apr 1;20(7):1832-7. [https://doi.org/10.1200/JCO.2002.07.045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11919241 PubMed] | + | # '''GOG 149:''' Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, Markman M, Benda J. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2002 Apr 1;20(7):1832-7. [https://doi.org/10.1200/JCO.2002.07.045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11919241/ PubMed] |
==Cisplatin & Mitomycin {{#subobject:c97b6f|Regimen=1}}== | ==Cisplatin & Mitomycin {{#subobject:c97b6f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:6e84ee|Variant=1}}=== | ===Regimen {{#subobject:6e84ee|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0959-8049(01)00178-2 Wagenaar et al. 2001] |
− | |style="background-color:#91cf61"|Phase | + | |NR |
+ | |style="background-color:#91cf61"|Phase 2 | ||
| style="background-color:#8c96c6" |ORR: 42% (95% CI: 26-61%) | | style="background-color:#8c96c6" |ORR: 42% (95% CI: 26-61%) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second''' | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second''' | ||
*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV push once on day 1, '''given first''' | *[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV push once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *1 liter NS over 1 hour once on day 1, prior to chemotherapy, then 1 liter NS over 1 hour once on day 1, after cisplatin |
− | *1 liter NS over 1 hour once on day 1, prior to chemotherapy, then 1 liter NS over 1 hour once on day 1, after | ||
*[[Furosemide (Lasix)]] (route/dose not specified) once on day 1, prior to chemotherapy | *[[Furosemide (Lasix)]] (route/dose not specified) once on day 1, prior to chemotherapy | ||
− | *[[Mannitol]] IV push once on day 1, prior to | + | *[[Mannitol]] IV push once on day 1, prior to cisplatin |
− | |||
'''28-day cycle for 9 cycles''' | '''28-day cycle for 9 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Gynecological Cancer Group. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix: a European Organisation for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. [https:// | + | # Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Gynecological Cancer Group. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix: a European Organisation for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. [https://doi.org/10.1016/s0959-8049(01)00178-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11527687/ PubMed] |
− | |||
==Cisplatin & Paclitaxel {{#subobject:aab02e|Regimen=1}}== | ==Cisplatin & Paclitaxel {{#subobject:aab02e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''isplatin | PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''isplatin | ||
<br>CP: '''<u>C</u>'''isplatin & '''<u>P</u>'''aclitaxel | <br>CP: '''<u>C</u>'''isplatin & '''<u>P</u>'''aclitaxel | ||
<br>TP: '''<u>T</u>'''axol (Paclitaxel) & '''<u>P</u>'''latinol (Cisplatin) | <br>TP: '''<u>T</u>'''axol (Paclitaxel) & '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 50/135, 3 hr paclitaxel {{#subobject:PYV4|Variant=1}}=== | ===Regimen variant #1, 50/135, 3 hr paclitaxel {{#subobject:PYV4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=3|[https:// | + | |rowspan=3|[https://doi.org/10.1056/NEJMoa1309748 Tewari et al. 2014 (GOG 240)] |
|rowspan=3|2009-2012 | |rowspan=3|2009-2012 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (C) |
|1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | |1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
− | |style="background-color:# | + | | style="background-color:#d73027" |Inferior OS<sup>1</sup> |
|- | |- | ||
− | |2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] | + | |2. [[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
Line 1,119: | Line 1,267: | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2017 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV once on day 1 | *[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycles until CR or indefinitely''' | '''21-day cycles until CR or indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 50/135, CI paclitaxel {{#subobject:bd6f7b|Variant=1}}=== | ===Regimen variant #2, 50/135, CI paclitaxel {{#subobject:bd6f7b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,135: | Line 1,285: | ||
|[https://doi.org/10.1200/jco.2004.04.170 Moore et al. 2004 (GOG 169)] | |[https://doi.org/10.1200/jco.2004.04.170 Moore et al. 2004 (GOG 169)] | ||
|1997-1999 | |1997-1999 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Cisplatin_monotherapy|Cisplatin]] | |[[#Cisplatin_monotherapy|Cisplatin]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (secondary endpoint)<br><br>Superior ORR (primary endpoint) |
|- | |- | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | ||
|rowspan=3|2003-2007 | |rowspan=3|2003-2007 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (C) |
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | |1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | ||
− | |style="background-color:#91cf60"|Seems to have superior PFS | + | |style="background-color:#91cf60"|Seems to have superior PFS (secondary endpoint) |
|- | |- | ||
|2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | |2. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |3. [[#Cisplatin_. | + | |3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]] |
− | |style="background-color:#d9ef8b"|Might have superior PFS | + | |style="background-color:#d9ef8b"|Might have superior PFS (secondary endpoint) |
|- | |- | ||
|[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)] | |[https://doi.org/10.1200/JCO.2014.58.4391 Kitagawa et al. 2015 (JCOG0505)] | ||
|2006-2009 | |2006-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | |[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | ||
|style="background-color:#eeee01"|Non-inferior OS | |style="background-color:#eeee01"|Non-inferior OS | ||
Line 1,159: | Line 1,309: | ||
|} | |} | ||
''Note: patients in JCOG0505 received a maximum of 6 cycles.'' | ''Note: patients in JCOG0505 received a maximum of 6 cycles.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 2 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 2 | ||
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | *[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*(varies depending on reference): | *(varies depending on reference): | ||
*[[Dexamethasone (Decadron)]] | *[[Dexamethasone (Decadron)]] | ||
*[[Diphenhydramine (Benadryl)]] | *[[Diphenhydramine (Benadryl)]] | ||
*H2 receptor antagonist such as [[Cimetidine (Tagamet)]] or [[Ranitidine (Zantac)]] | *H2 receptor antagonist such as [[Cimetidine (Tagamet)]] or [[Ranitidine (Zantac)]] | ||
− | *Prophylactic [[:Category:Emesis_prevention|antiemetics]] | + | *Prophylactic [[:Category:Emesis_prevention|antiemetics]] |
− | *"Adequate IV hydration and electrolyte replacement" | + | *"Adequate IV [[:Category:Hydration|hydration]] and electrolyte replacement" |
− | |||
'''21-day cycles; if not responding, given for maximum of 6 cycles.''' | '''21-day cycles; if not responding, given for maximum of 6 cycles.''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 50/175 {{#subobject:ccc92b|Variant=1}}=== | ===Regimen variant #3, 50/175 {{#subobject:ccc92b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=3|[https:// | + | |rowspan=3|[https://doi.org/10.1056/NEJMoa1309748 Tewari et al. 2014 (GOG 240)] |
|rowspan=3|2009-2012 | |rowspan=3|2009-2012 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (C) |
|1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | |1. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
− | |style="background-color:# | + | | style="background-color:#d73027" |Inferior OS<sup>1</sup> |
|- | |- | ||
− | |2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] | + | |2. [[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | |3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br> | ||
+ | ''Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | '''21-day cycle for 6 or more cycles (see note)''' | |
− | '''21-day cycles | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains | + | # '''GOG 169:''' Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. [https://doi.org/10.1200/jco.2004.04.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284262/ PubMed] |
<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | ||
− | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains | + | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077] |
− | # '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https:// | + | # '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062] |
− | ## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https:// | + | ## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed] |
− | # '''JCOG0505:''' Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.58.4391 link to original article] '''contains | + | ## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed] |
− | + | # '''JCOG0505:''' Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.58.4391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732161/ PubMed] [https://clinicaltrials.gov/study/NCT00295789 NCT00295789] | |
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
==Cisplatin, Paclitaxel, Bevacizumab {{#subobject:PYR1|Regimen=1}}== | ==Cisplatin, Paclitaxel, Bevacizumab {{#subobject:PYR1|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | CP+Bev: '''<u>C</u>'''isplatin, '''<u>P</u>'''aclitaxel, '''<u>Bev</u>'''acizumab |
+ | {| class="wikitable" style="color:black; background-color:#42f584" | ||
+ | |<small>'''ESMO-preferred (I-A, 2017)'''</small> | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 135 mg/m<sup>2</sup> paclitaxel {{#subobject:PYV1|Variant=1}}=== | ===Regimen variant #1, 135 mg/m<sup>2</sup> paclitaxel {{#subobject:PYV1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,223: | Line 1,386: | ||
|- | |- | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|rowspan=3|2009-2012 | |rowspan=3|2009-2012 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
− | |style="background-color:# | + | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 16.8 vs 13.3 mo<br>(HR 0.77, 95% CI 0.62-0.95) |
|- | |- | ||
− | |2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] | + | |2. [[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] |
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup> |
|- | |- | ||
|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | |3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | ||
Line 1,235: | Line 1,402: | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy is based on the 2017 update.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
Line 1,241: | Line 1,409: | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles until CR or indefinitely''' | '''21-day cycles until CR or indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 175 mg/m<sup>2</sup> paclitaxel {{#subobject:ca025d|Variant=1}}=== | ===Regimen variant #2, 175 mg/m<sup>2</sup> paclitaxel {{#subobject:ca025d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,253: | Line 1,421: | ||
|- | |- | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|rowspan=3|2009-2012 | |rowspan=3|2009-2012 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
− | |style="background-color:# | + | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 16.8 vs 13.3 mo<br>(HR 0.77, 95% CI 0.62-0.95) |
|- | |- | ||
− | |2. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] | + | |2. [[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] |
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup> |
|- | |- | ||
|3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | |3. [[#Paclitaxel.2C_Topotecan.2C_Bevacizumab|Paclitaxel, Topotecan, Bevacizumab]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Pembrolizumab|CP, Bevacizumab, Pembrolizumab]]<br>1c. [[#Cisplatin.2C_Paclitaxel.2C_Pembrolizumab|Cisplatin, Paclitaxel, Pembrolizumab]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab.2C_Pembrolizumab|Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)] | ||
+ | |2018-10-08 to 2021-08-20 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#ABCP|ABCP]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Atezolizumab.2C_Bevacizumab|Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS/OS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for this comparison in GOG 240 is based on the 2017 update.''<br> |
+ | ''Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. The decision to give bevacizumab in KEYNOTE-826 was at the discretion of the treating institution and was not a randomization.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
Line 1,271: | Line 1,457: | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 6 or more cycles (see note)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062] | ||
+ | ## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed] | ||
+ | ## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed] | ||
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
+ | #'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839] | ||
− | '''21-day cycles | + | ==Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab {{#subobject:bcc2hw|Regimen=1}}== |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:51hby4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)02405-4 Oaknin et al. 2023 (BEATcc)] | ||
+ | |2018-10-08 to 2021-08-20 | ||
+ | |style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1b. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 32.1 vs 22.8 mo<br>(HR 0.68, 95% CI 0.52-0.88)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 13.7 vs 10.4 mo<br>(HR 0.62, 95% CI 0.49-0.78) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''BEATcc:''' Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. [https://doi.org/10.1016/s0140-6736(23)02405-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38048793/ PubMed] [https://clinicaltrials.gov/study/NCT03556839 NCT03556839] | ||
+ | ==Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab {{#subobject:gac765|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:18ghuh|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br> | ||
+ | ''Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Pembrolizumab (Keytruda)]] as follows: | ||
+ | **Cycles 1 up to 35: 200 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # ''' | + | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] |
− | ## ''' | + | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] |
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
− | ==Cisplatin | + | ==Cisplatin, Paclitaxel, Pembrolizumab {{#subobject:chge55|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:aggc1h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112435 Colombo et al. 2021 (KEYNOTE-826)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-306-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|CP & Bevacizumab]]<br>1c. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]]<br>1d. [[#Cisplatin.2C_Paclitaxel.2C_Bevacizumab|Cisplatin, Paclitaxel, Bevacizumab]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 26.4 vs 16.8 mo<br>(HR 0.63, 95% CI 0.52-0.77) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update for all patients.''<br> | ||
+ | ''Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6 (see note): 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
+ | '''21-day cycle for up to 35 cycles (2 years)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''KEYNOTE-826:''' Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. [https://doi.org/10.1056/nejmoa2112435 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34534429/ PubMed] [https://clinicaltrials.gov/study/NCT03635567 NCT03635567] | ||
+ | ##'''HRQoL analysis:''' Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. [https://doi.org/10.1016/s1470-2045(23)00052-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36878237/ PubMed] | ||
+ | ##'''Update:''' Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. [https://doi.org/10.1200/jco.23.00914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37910822/ PubMed] | ||
+ | ==Cisplatin & Topotecan {{#subobject:e399c6|Regimen=1}}== | ||
TC: '''<u>T</u>'''opotecan & '''<u>C</u>'''isplatin | TC: '''<u>T</u>'''opotecan & '''<u>C</u>'''isplatin | ||
<br>CT: '''<u>C</u>'''isplatin & '''<u>T</u>'''opotecan | <br>CT: '''<u>C</u>'''isplatin & '''<u>T</u>'''opotecan | ||
− | ===Regimen {{#subobject:f703f4|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 6 cycles {{#subobject:f703f4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,295: | Line 1,591: | ||
|rowspan=2|[https://doi.org/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)] | |rowspan=2|[https://doi.org/10.1200/jco.2005.10.021 Long et al. 2005 (GOG 179)] | ||
|rowspan=2|1999-2002 | |rowspan=2|1999-2002 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|1. [[#Cisplatin_monotherapy|Cisplatin]] | |1. [[#Cisplatin_monotherapy|Cisplatin]] | ||
− | |style="background-color:#91cf60"|Seems to have superior OS | + | |style="background-color:#91cf60"|Seems to have superior OS (primary endpoint)<br>Median OS: 9.4 vs 6.5 mo<br>(RR 0.76, 95% CI 0.59-0.98) |
|- | |- | ||
− | |2. MVAC | + | |2. [[#MVAC_999|MVAC]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | ||
|rowspan=3|2003-2007 | |rowspan=3|2003-2007 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | |1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
Line 1,311: | Line 1,607: | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |3. [[#Cisplatin_. | + | |3. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1007/s12032-010-9700-3 Coronel et al. 2010 (006/027/ICI)] |
|2007-2009 | |2007-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |CT + HV | + | |[[#Cisplatin.2C_Topotecan.2C_Hydralazine.2C_Valproate_888|CT + HV]] |
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second''' | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second''' | ||
*[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3, '''given first''' | *[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3, '''given first''' | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 6 to 9 cycles {{#subobject:f76294|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ygyno.2024.03.002 Gass et al. 2024 (AGO-Zervix-1)] | ||
+ | |2007-01 to 2012-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|TP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 12 vs 9.6 mo | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second''' | ||
+ | *[[Topotecan (Hycamtin)]] 0.75 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3, '''given first''' | ||
+ | '''21-day cycle for 6 up to 9 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. --> | <!-- Presented in abstract form at the Annual Meeting of the Society of Gynecologic Oncologists, San Diego, CA, February 8, 2004. --> | ||
− | # '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains | + | # '''GOG 179:''' Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.10.021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15911865/ PubMed] [https://clinicaltrials.gov/study/NCT00003945 NCT00003945] |
<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | ||
− | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains | + | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077] |
− | # '''006/027/ICI:''' Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M, Vidal S, Dueñas-González A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer: preliminary results. Med Oncol. 2011 Dec;28 Suppl 1:S540-6. Epub 2010 Oct 8. [https:// | + | # '''006/027/ICI:''' Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M, Vidal S, Dueñas-González A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer: preliminary results. Med Oncol. 2011 Dec;28 Suppl 1:S540-6. Epub 2010 Oct 8. [https://doi.org/10.1007/s12032-010-9700-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20931299/ PubMed] [https://clinicaltrials.gov/study/NCT00532818 NCT00532818] |
+ | #'''AGO-Zervix-1:''' Gass P, Thiel FC, Häberle L, Ackermann S, Theuser AK, Hummel N, Boehm S, Kimmig R, Reinthaller A, Becker S, Hilpert F, Janni W, Vergote I, Harter P, Emons J, Hein A, Beckmann MW, Fasching PA, Pöschke P; AGO Uterus Commission. Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer. Gynecol Oncol. 2024 Apr;183:25-32. Epub 2024 Mar 14. [https://doi.org/10.1016/j.ygyno.2024.03.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38490057/ PubMed] [https://clinicaltrials.gov/study/NCT01405235 NCT01405235] | ||
− | ==Cisplatin & Vinorelbine {{#subobject:176775|Regimen=1}}== | + | ==Cisplatin & Vinorelbine (CVb) {{#subobject:176775|Regimen=1}}== |
− | + | CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine | |
− | + | <br>VC: '''<u>V</u>'''inorelbine, '''<u>C</u>'''isplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | VC: '''<u>V</u>'''inorelbine, '''<u>C</u>'''isplatin | ||
===Regimen {{#subobject:e442f7|Variant=1}}=== | ===Regimen {{#subobject:e442f7|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,350: | Line 1,667: | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ Monk et al. 2009 (GOG 204)] | ||
|rowspan=3|2003-2007 | |rowspan=3|2003-2007 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | |1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|2. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |2. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
− | |style="background-color:#fee08b"|Might have inferior PFS | + | |style="background-color:#fee08b"|Might have inferior PFS (primary endpoint) |
|- | |- | ||
|3. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | |3. [[#Cisplatin_.26_Topotecan|Cisplatin & Topotecan]] | ||
Line 1,361: | Line 1,678: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycles; if not responding, given for maximum of 6 cycles''' | '''21-day cycles; if not responding, given for maximum of 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | ||
− | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains | + | # '''GOG 204:''' Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.21.8909 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19720909/ PubMed] [https://clinicaltrials.gov/study/NCT00064077 NCT00064077] |
− | |||
==Ifosfamide monotherapy {{#subobject:1d18ed|Regimen=1}}== | ==Ifosfamide monotherapy {{#subobject:1d18ed|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:962339|Variant=1}}=== | ===Regimen {{#subobject:962339|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1007/BF00273403 Coleman et al. 1986] |
− | |style="background-color:#91cf61"|Phase | + | |NR |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1006/gyno.1993.1084 Sutton et al. 1993b] |
− | |style="background-color:#91cf61"|Phase | + | |1985-07 to 1990-12 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s0002-9378(12)90824-8 Sutton et al. 1993a] |
− | |style="background-color:#91cf61"|Phase | + | |1988-01 to 1990-02 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5 | + | *[[Ifosfamide (Ifex)]] by the following exposure-based criteria: |
− | * | + | *No previous pelvic radiation or other chemotherapy: 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | + | *Previous pelvic radiation or other chemotherapy: 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5 | |
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Mesna (Mesnex)]] at 20% of ifosfamide dose (for example, 300 mg/m<sup>2</sup> for 1500 mg/m<sup>2</sup> dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5 | *[[Mesna (Mesnex)]] at 20% of ifosfamide dose (for example, 300 mg/m<sup>2</sup> for 1500 mg/m<sup>2</sup> dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Ifosfamide (Ifex)]] dose could be increased by 300 mg/m<sup>2</sup> or decreased by 20% depending on toxicity | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, Wiltshaw E. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. [https:// | + | # Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, Wiltshaw E. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. [https://doi.org/10.1007/BF00273403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3802384/ PubMed] |
− | # Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY; Gynecologic Oncology Group. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. [https:// | + | # Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY; Gynecologic Oncology Group. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. [https://doi.org/10.1016/s0002-9378(12)90824-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8456884/ PubMed] |
− | # Sutton GP, Blessing JA, DiSaia PJ, McGuire WP; Gynecologic Oncology Group. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. [ | + | # Sutton GP, Blessing JA, DiSaia PJ, McGuire WP; Gynecologic Oncology Group. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. [https://doi.org/10.1006/gyno.1993.1084 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8482560/ PubMed] |
− | |||
==Paclitaxel monotherapy {{#subobject:635f43|Regimen=1}}== | ==Paclitaxel monotherapy {{#subobject:635f43|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 135 mg/m<sup>2</sup> {{#subobject:723bf0|Variant=1}}=== | ===Regimen variant #1, 135 mg/m<sup>2</sup> {{#subobject:723bf0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1996.14.3.792 McGuire et al. 1996] | |[https://doi.org/10.1200/jco.1996.14.3.792 McGuire et al. 1996] | ||
− | |style="background-color:#91cf61"|Phase | + | |1990 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001] | |[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001] | ||
− | |style="background-color:#91cf61"|Phase | + | |1994 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: this was the dosage used for patients with previous pelvic radiation.'' | ''Note: this was the dosage used for patients with previous pelvic radiation.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | *[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to paclitaxel | |
− | ====Supportive | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to | + | *[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to | ||
− | *[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Paclitaxel (Taxol)]] dose could be changed to 110 or 200 mg/m<sup>2</sup> depending on toxicity | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 170 mg/m<sup>2</sup> {{#subobject:6eac87|Variant=1}}=== | ===Regimen variant #2, 170 mg/m<sup>2</sup> {{#subobject:6eac87|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1996.14.3.792 McGuire et al. 1996] | |[https://doi.org/10.1200/jco.1996.14.3.792 McGuire et al. 1996] | ||
− | |style="background-color:#91cf61"|Phase | + | |1990 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001] | |[https://doi.org/10.1200/jco.2001.19.5.1275 Curtin et al. 2001] | ||
− | |style="background-color:#91cf61"|Phase | + | |1994 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] 170 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | + | *[[Paclitaxel (Taxol)]] by the following exposure-based criteria: |
− | ** | + | **No previous pelvic radiation: 170 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 |
− | + | **Previous pelvic radiation: 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to | + | *[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Paclitaxel (Taxol)]] dose could be changed to 110 or 200 mg/m<sup>2</sup> depending on toxicity | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 250 mg/m<sup>2</sup> {{#subobject:4c3e15|Variant=1}}=== | ===Regimen variant #3, 250 mg/m<sup>2</sup> {{#subobject:4c3e15|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://aacrjournals.org/clincancerres/article/2/8/1285/33159/Activity-of-paclitaxel-in-advanced-or-recurrent Kudelka et al. 1996] |
− | |style="background-color:#91cf61"|Phase | + | |NR |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV over 3 hours on day 1 | + | *[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV over 3 hours once on day 1 |
− | + | ====Supportive therapy==== | |
− | + | *[[Dexamethasone (Decadron)]] 20 mg PO for two doses on day 1; 14 and 7 hours prior to paclitaxel | |
− | ====Supportive | + | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 60 minutes prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg PO for two doses on day 1; 14 and 7 hours prior to | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 60 minutes prior to paclitaxel |
− | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 60 minutes prior to | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 2, 24 hours after paclitaxel, given until day 19 or until ANC greater or equal to 10,000/μL |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 60 minutes prior to | ||
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 2, 24 hours after | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Paclitaxel (Taxol)]] dose could be changed to 275, 225, or 200 mg/m<sup>2</sup> depending on toxicity | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G; Gynecologic Oncology Group. Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [https://doi.org/10.1200/jco.1996.14.3.792 link to original article] '''contains | + | # McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G; Gynecologic Oncology Group. Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. [https://doi.org/10.1200/jco.1996.14.3.792 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8622025/ PubMed] |
− | # Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. [ | + | # Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. [https://aacrjournals.org/clincancerres/article/2/8/1285/33159/Activity-of-paclitaxel-in-advanced-or-recurrent link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9816298/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | ## '''Update:''' Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. [https://pubmed.ncbi.nlm.nih.gov/9311440 PubMed] | + | ## '''Update:''' Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. [https://doi.org/10.1097/00001813-199708000-00002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9311440/ PubMed] |
− | # Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD; Gynecologic Oncology Group. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [https://doi.org/10.1200/jco.2001.19.5.1275 link to original article] '''contains | + | # Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD; Gynecologic Oncology Group. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. [https://doi.org/10.1200/jco.2001.19.5.1275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11230468/ PubMed] |
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− | |||
− | |||
==Paclitaxel, Topotecan, Bevacizumab {{#subobject:PYR3|Regimen=1}}== | ==Paclitaxel, Topotecan, Bevacizumab {{#subobject:PYR3|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TP+Bev: '''<u>T</u>'''opotecan, '''<u>P</u>'''aclitaxel, '''<u>Bev</u>'''acizumab | TP+Bev: '''<u>T</u>'''opotecan, '''<u>P</u>'''aclitaxel, '''<u>Bev</u>'''acizumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:PYV3|Variant=1}}=== | ===Regimen {{#subobject:PYV3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,539: | Line 1,830: | ||
|- | |- | ||
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | |rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ Tewari et al. 2014 (GOG 240)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-36-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|rowspan=3|2009-2012 | |rowspan=3|2009-2012 | ||
− | |rowspan=3 style="background-color:#1a9851"|Phase | + | |rowspan=3 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | |1. [[#Cisplatin_.26_Paclitaxel_2|Cisplatin & Paclitaxel]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
Line 1,547: | Line 1,842: | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | |3. [[#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] | + | |3. [[Cervical_cancer_-_historical#Paclitaxel_.26_Topotecan|Paclitaxel & Topotecan]] |
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS<sup>1</sup> |
|- | |- | ||
|} | |} | ||
− | ''Note: in the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens | + | ''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br> |
+ | ''Note: in the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
Line 1,557: | Line 1,854: | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https:// | + | # '''GOG 240:''' Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. [https://doi.org/10.1056/NEJMoa1309748 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1309748/suppl_file/nejmoa1309748_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552320/ PubMed] [https://clinicaltrials.gov/study/NCT00803062 NCT00803062] |
− | ## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https:// | + | ## '''Update:''' Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. [https://doi.org/10.1016/s0140-6736(17)31607-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5714293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28756902/ PubMed] |
− | + | ## '''Update:''' Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. [https://doi.org/10.1016/j.ygyno.2023.01.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898292/ PubMed] | |
==Topotecan monotherapy {{#subobject:720120|Regimen=1}}== | ==Topotecan monotherapy {{#subobject:720120|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, q3wk {{#subobject:be1724|Variant=1}}=== | ===Regimen variant #1, q3wk {{#subobject:be1724|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1006/gyno.2000.5807 Bookman et al. 2000 (GOG 127-F)] |
− | |style="background-color:#91cf61"|Phase | + | |1994-12 to NR |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | *[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, q4wk {{#subobject:469fbe|Variant=1}}=== | ===Regimen variant #2, q4wk {{#subobject:469fbe|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1006/gyno.2000.6024 Muderspach et al. 2001 (GOG 76-U)] |
− | |style="background-color:#91cf61"|Phase | + | |1994-01 to 1995-12 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | *[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA; Gynecologic Oncology Group. Topotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [ | + | # Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA; Gynecologic Oncology Group. Topotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. [https://doi.org/10.1006/gyno.2000.5807 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10831357/ PubMed] |
− | # Muderspach LI, Blessing JA, Levenback C, Moore JL Jr; Gynecologic Oncology Group. A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Gxroup study. Gynecol Oncol. 2001 May;81(2):213-5. [ | + | # '''GOG 76-U:''' Muderspach LI, Blessing JA, Levenback C, Moore JL Jr; Gynecologic Oncology Group. A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Gxroup study. Gynecol Oncol. 2001 May;81(2):213-5. [https://doi.org/10.1006/gyno.2000.6024 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11354055/ PubMed] |
− | |||
==Vinorelbine monotherapy {{#subobject:b92b24|Regimen=1}}== | ==Vinorelbine monotherapy {{#subobject:b92b24|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e1af3|Variant=1}}=== | ===Regimen {{#subobject:e1af3|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1998.16.3.1094 Morris et al. 1998] | |[https://doi.org/10.1200/jco.1998.16.3.1094 Morris et al. 1998] | ||
− | |style="background-color:#91cf61"|Phase | + | |1993-1995 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|ORR: 18% | |ORR: 18% | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1 | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''7-day cycles''' | '''7-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [https://doi.org/10.1200/jco.1998.16.3.1094 link to original article] '''contains | + | # Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. [https://doi.org/10.1200/jco.1998.16.3.1094 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9508195/ PubMed] |
− | |||
=Advanced or metastatic disease, subsequent lines of therapy= | =Advanced or metastatic disease, subsequent lines of therapy= | ||
==Bevacizumab monotherapy {{#subobject:1da8f9|Regimen=1}}== | ==Bevacizumab monotherapy {{#subobject:1da8f9|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:67b93c|Variant=1}}=== | ===Regimen {{#subobject:67b93c|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667811/ Monk et al. 2009 (GOG 227-C)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667811/ Monk et al. 2009 (GOG 227-C)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2002-2006 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 39th Annual Meeting of the Society of Gynecologic Oncologists, March 9-12, 2008, Tampa, FL. --> | <!-- Presented in part at the 39th Annual Meeting of the Society of Gynecologic Oncologists, March 9-12, 2008, Tampa, FL. --> | ||
− | # Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD; Gynecologic Oncology Group. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. [https://doi.org/10.1200/jco.2008.18.9043 link to original article] '''contains | + | # Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD; Gynecologic Oncology Group. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. [https://doi.org/10.1200/jco.2008.18.9043 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667811/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19139430/ PubMed] |
+ | ==Cemiplimab monotherapy {{#subobject:1dhg19|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:684026|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-361-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Pemetrexed_monotherapy|Pemetrexed]]<br>1b. [[#Topotecan_monotherapy_2|Topotecan]]<br>1c. [[#Irinotecan_monotherapy|Irinotecan]]<br>1d. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1e. [[#Vinorelbine_monotherapy_2|Vinorelbine]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 12 vs 8.5 mo<br>(HR 0.69, 95% CI 0.56-0.84) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Immunotherapy==== | ||
+ | *[[Cemiplimab (Libtayo)]] 350 mg IV once on day 1 | ||
+ | '''21-day cycle for up to 32 cycles (96 weeks)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | ||
==Cisplatin & Gemcitabine (GC) {{#subobject:d9cdf3|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) {{#subobject:d9cdf3|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin | GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:684026|Variant=1}}=== | ===Regimen {{#subobject:684026|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2005.09.009 Brewer et al. 2006] |
− | |style="background-color:#91cf61"|Phase | + | |2001-2002 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once on day 1, '''given first''' | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once on day 1, '''given first''' | ||
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second''' | *[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second''' | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL; Gynecologic Oncology Group. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. [ | + | # Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL; Gynecologic Oncology Group. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. [https://doi.org/10.1016/j.ygyno.2005.09.009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16271750/ PubMed] |
− | |||
==Docetaxel monotherapy {{#subobject:95153c|Regimen=1}}== | ==Docetaxel monotherapy {{#subobject:95153c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen variant #1, 36 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:328695|Variant=1}}=== | ===Regimen variant #1, 36 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:328695|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2008.06.013 Garcia et al. 2008] |
− | |style="background-color:#91cf61"|Phase | + | |2004-07 to 2005-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Docetaxel (Taxotere)]] 36 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15 | *[[Docetaxel (Taxotere)]] 36 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Dexamethasone (Decadron)]] 8 mg PO the evening before, morning of, and evening of each dose of docetaxel | *[[Dexamethasone (Decadron)]] 8 mg PO the evening before, morning of, and evening of each dose of docetaxel | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 100 mg/m<sup>2</sup>, q3wk {{#subobject:744f01|Variant=1}}=== | ===Regimen variant #2, 100 mg/m<sup>2</sup>, q3wk {{#subobject:744f01|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1097/coc.0b013e31803377c8 Garcia et al. 2007] |
− | |style="background-color:#91cf61"|Phase | + | |2002-06 to 2004-12 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 2007 Aug;30(4):428-31. [ | + | # Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 2007 Aug;30(4):428-31. [https://doi.org/10.1097/coc.0b013e31803377c8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17762444/ PubMed] |
− | # Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. [ | + | # Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. [https://doi.org/10.1016/j.ygyno.2008.06.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18675446/ PubMed] |
− | |||
==FULV {{#subobject:e38061|Regimen=1}}== | ==FULV {{#subobject:e38061|Regimen=1}}== | ||
− | + | FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin | ||
===Regimen variant #1, 1850/200 {{#subobject:937680|Variant=1}}=== | ===Regimen variant #1, 1850/200 {{#subobject:937680|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1097/00000421-199610000-00002 Look et al. 1996] |
− | |style="background-color:#91cf61"|Phase | + | |1990-1992 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1006/gyno.1997.4886 Look et al. 1997] |
− | |style="background-color:#91cf61"|Phase | + | |1993-1995 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: it is not entirely clear from these publications whether leucovorin is given on day 1 only, versus on days 1 to 5.'' | ''Note: it is not entirely clear from these publications whether leucovorin is given on day 1 only, versus on days 1 to 5.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 5, '''given second''' | *[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 5, '''given second''' | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV bolus once on day 1 (see note), '''given first''' |
− | |||
'''28-day cycle for 2 cycles, then 35-day cycles''' | '''28-day cycle for 2 cycles, then 35-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 2125/100 {{#subobject:c76c92|Variant=1}}=== | ===Regimen variant #2, 2125/100 {{#subobject:c76c92|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1097/00000421-199212000-00007 Look et al. 1992] |
− | |style="background-color:#91cf61"|Phase | + | |1989-09 to 1990-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second''' | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given first''' |
− | |||
'''28-day cycle for 2 cycles, then 35-day cycles''' | '''28-day cycle for 2 cycles, then 35-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH; Gynecologic Oncology Group. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. [https://pubmed.ncbi.nlm.nih.gov/1449112 PubMed] | + | # Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH; Gynecologic Oncology Group. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. [https://doi.org/10.1097/00000421-199212000-00007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1449112/ PubMed] |
− | # Look KY, Blessing JA, Gallup DG, Lentz SS; Gynecologic Oncology Group. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. [https:// | + | # Look KY, Blessing JA, Gallup DG, Lentz SS; Gynecologic Oncology Group. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. [https://doi.org/10.1097/00000421-199610000-00002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8823469/ PubMed] |
− | # Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA; Gynecologic Oncology Group. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. [ | + | # Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA; Gynecologic Oncology Group. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. [https://doi.org/10.1006/gyno.1997.4886 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9441772/ PubMed] |
− | |||
==Gemcitabine monotherapy {{#subobject:313d78|Regimen=1}}== | ==Gemcitabine monotherapy {{#subobject:313d78|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:9f6038|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1006/gyno.1999.5671 Schilder et al. 2000 (GOG 127-K)] | ||
+ | |NR | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ygyno.2004.09.027 Schilder et al. 2005] | ||
+ | |NR | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | {| class="wikitable" style="width: | + | ====Chemotherapy==== |
− | !style="width: | + | *[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 |
− | !style="width: | + | '''28-day cycles''' |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:7tyg1h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] |
− | |style="background-color:# | + | |2017-2020 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cemiplimab_monotherapy|Cemiplimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |[ | + | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] |
− | |style="background-color:# | + | |2021-2023 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Gemcitabine (Gemzar)]] | + | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | + | '''21-day cycles''' | |
− | ''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS; Gynecologic Oncology Group. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Feb;76(2):204-7. [ | + | # '''GOG 127-K:''' Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS; Gynecologic Oncology Group. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Feb;76(2):204-7. [https://doi.org/10.1006/gyno.1999.5671 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10637071/ PubMed] |
− | # Schilder RJ, Blessing J, Cohn DE; Gynecologic Oncology Group. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. [ | + | # Schilder RJ, Blessing J, Cohn DE; Gynecologic Oncology Group. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. [https://doi.org/10.1016/j.ygyno.2004.09.027 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15589587/ PubMed] |
− | + | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | |
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
==Irinotecan monotherapy {{#subobject:e80134|Regimen=1}}== | ==Irinotecan monotherapy {{#subobject:e80134|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:91yugf|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cemiplimab_monotherapy|Cemiplimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject:fe2b8e|Variant=1}}=== | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | !style="width: | + | ====Chemotherapy==== |
− | !style="width: | + | *[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
+ | '''42-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:fe2b8e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1997.15.2.625 Verschraegen et al. 1997] | |[https://doi.org/10.1200/jco.1997.15.2.625 Verschraegen et al. 1997] | ||
− | |style="background-color:#91cf61"|Phase | + | |1993-1995 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22 | *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion | *[[Diphenhydramine (Benadryl)]] 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion | ||
− | *Atropine 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion | + | *[[Atropine (Atropen)]] 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion |
*[[Loperamide (Imodium)]] 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions | *[[Loperamide (Imodium)]] 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions | ||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. [https://doi.org/10.1200/jco.1997.15.2.625 link to original article] '''contains | + | # Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. [https://doi.org/10.1200/jco.1997.15.2.625 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9053486/ PubMed] |
− | + | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | |
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}== | ==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:7b36e9|Variant=1}}=== | ===Regimen {{#subobject:7b36e9|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,822: | Line 2,207: | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/JCO.18.01265 Chung et al. 2019 (KEYNOTE-158)] | + | |[https://doi.org/10.1200/JCO.18.01265 Chung et al. 2019 (KEYNOTE-158<sub>cervical</sub>)] |
− | |2016 | + | |2016-01-27 to 2016-08-18 |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 (RT) |
|- | |- | ||
|} | |} | ||
+ | ''Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1 | *[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1 | ||
− | |||
'''21-day cycle for up to 35 cycles (2 years)''' | '''21-day cycle for up to 35 cycles (2 years)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- # '''Abstract:''' Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. [https://doi.org/10.1200/JCO.2017.35.15_suppl.5514 link to abstract] --> | <!-- # '''Abstract:''' Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. [https://doi.org/10.1200/JCO.2017.35.15_suppl.5514 link to abstract] --> | ||
− | # '''KEYNOTE-158:''' Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Epub 2019 Apr 3. [https://doi.org/10.1200/JCO.18.01265 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30943124 PubMed] | + | # '''KEYNOTE-158<sub>cervical</sub>:''' Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Epub 2019 Apr 3. [https://doi.org/10.1200/JCO.18.01265 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30943124/ PubMed] [https://clinicaltrials.gov/study/NCT02628067 NCT02628067] |
− | |||
==Pemetrexed monotherapy {{#subobject:57456b|Regimen=1}}== | ==Pemetrexed monotherapy {{#subobject:57456b|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:gh4w1h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cemiplimab_monotherapy|Cemiplimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject:db8999|Variant=1}}=== | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | !style="width: | + | ====Chemotherapy==== |
− | !style="width: | + | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:db8999|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2008.03.009 Miller et al. 2008] |
− | |style="background-color:#91cf61"|Phase | + | |2004-2006 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Pemetrexed (Alimta)]] 900 mg/m<sup>2</sup> IV over 10 minutes once on day 1 | *[[Pemetrexed (Alimta)]] 900 mg/m<sup>2</sup> IV over 10 minutes once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy |
− | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 7 days | + | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM every 9 weeks |
− | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once, 7 days | + | *[[Dexamethasone (Decadron)]] 4 mg PO twice per day the day before, the day of, and day after pemetrexed |
− | *[[Dexamethasone (Decadron)]] 4 mg PO twice per day the day before, the day of, and day after | ||
*No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed | *No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. [https://doi.org/10.1016/j.ygyno.2008.03.009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18455781/ PubMed] | ||
+ | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | ||
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
+ | ==Tisotumab vedotin monotherapy {{#subobject:2sbn6b|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ghg72h|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(21)00056-5 Coleman et al. 2021 (innovaTV 204)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-299-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-06-12 to 2019-04-11 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | ||
+ | |1a. [[#Pemetrexed_monotherapy|Pemetrexed]]<br>1b. [[#Topotecan_monotherapy_2|Topotecan]]<br>1c. [[#Irinotecan_monotherapy|Irinotecan]]<br>1d. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1e. [[#Vinorelbine_monotherapy_2|Vinorelbine]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 11.5 vs 9.5 mo<br>(HR 0.70, 95% CI 0.54-0.89) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Tisotumab vedotin (Tivdak)]] 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #'''innovaTV 204:''' Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. Epub 2021 Apr 9. [https://doi.org/10.1016/s1470-2045(21)00056-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33845034/ PubMed] [https://clinicaltrials.gov/study/NCT03438396 NCT03438396] |
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
− | == | + | ==Topotecan monotherapy {{#subobject:218ug1|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:91yg1h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cemiplimab_monotherapy|Cemiplimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:7tyg1h|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Dosing information is from CT.gov.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Topotecan (Hycamtin)]] 1.25 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | ||
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
+ | ==Vinorelbine monotherapy {{#subobject:2186af|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ba6a7e|Variant=1}}=== | ===Regimen {{#subobject:ba6a7e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2003.10.045 Muggia et al. 2004] |
− | |style="background-color:#91cf61"|Phase | + | |1997-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
|ORR: 14% (95% CI 5-27%) | |ORR: 14% (95% CI 5-27%) | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ygyno.2004.09.028 Muggia et al. 2005] |
− | |style="background-color:#91cf61"|Phase | + | |1997-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
|ORR: 7% | |ORR: 7% | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2112187 Tewari et al. 2022 (EMPOWER-Cervical 1)] | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cemiplimab_monotherapy|Cemiplimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://www.clinicaltrials.gov/study/NCT04697628 Awaiting publication (innovaTV 301)] | ||
+ | |2021-2023 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tisotumab_vedotin_monotherapy|Tisotumab vedotin]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. [ | + | # Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. [https://doi.org/10.1016/j.ygyno.2003.10.045 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14766259/ PubMed] |
− | # Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Jan;96(1):108-11. [ | + | # Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Jan;96(1):108-11. [https://doi.org/10.1016/j.ygyno.2004.09.028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15589588/ PubMed] |
− | + | #'''EMPOWER-Cervical 1:''' Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. [https://doi.org/10.1056/nejmoa2112187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35139273/ PubMed] [https://clinicaltrials.gov/study/NCT03257267 NCT03257267] | |
+ | #'''innovaTV 301:''' [https://clinicaltrials.gov/study/NCT04697628 NCT04697628] | ||
[[Category:Cervical cancer regimens]] | [[Category:Cervical cancer regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Gynecologic cancers]] | [[Category:Gynecologic cancers]] |
Revision as of 11:32, 2 July 2024
Section editor | |
---|---|
Alaina J. Brown, MD, MPH Vanderbilt University Nashville, TN, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
48 regimens on this page
66 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2022: Chuang et al. Management and Care of Patients With Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update PubMed
ESMO
- 2018: Marth et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2017: Marth et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Colombo et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Haie-Meder et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Haie-Meder et al. Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Haie-Meder et al. Cervical cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN Guidelines - Cervical Cancer
- 2019: Koh et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2015: Koh et al. Cervical Cancer, Version 2.2015 PubMed
- 2013: Koh et al. Cervical cancer. PubMed
- 2010: Greer et al. Cervical cancer. PubMed
- 2008: Greer et al. Cervical cancer. PubMed
- 2004: Teng et al. Cervical cancer guidelines. Clinical practice guidelines in oncology. PubMed
Neoadjuvant chemotherapy
Cisplatin & Paclitaxel
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Park et al. 2004 | 2000-10 to 2002-01 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV over 2 hours once on day 1, given second
- Paclitaxel (Taxol) 60 mg/m2 IV over 3 hours once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron) 20 mg PO twice on day 1; 12 and 6 hours prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Antiemetics before and 3 days after chemotherapy
10-day cycle for 3 cycles
Subsequent treatment
- Clinical response assessed after 3 cycles with pelvic examination and MRI. Treatment followed by surgery or radiation therapy.
References
- Park DC, Kim JH, Lew YO, Kim DH, Namkoong SE. Phase II trial of neoadjuvant paclitaxel and cisplatin in uterine cervical cancer. Gynecol Oncol. 2004 Jan;92(1):59-63. link to original article contains dosing details in manuscript PubMed
Definitive therapy for locally advanced disease
Brachytherapy protocol
Regimen
To be completed
Radiotherapy
- Intracavitary brachytherapy with radium or its equivalent by the following study-specific criteria:
- Pearcey et al. 2002: See paper for details
- GOG 120, stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy
- B9E-MC-JHQS & Sehouli et al. 2012: 30 to 3500 cGy delivered to point A
- GOG 219: 35 to 4360 cGy to point A
- GOG 120, stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
- Patients that could not receive brachytherapy underwent additional external_beam_radiotherapy for a total dose of 6120 cGy
- GOG 123: 3000 cGy to point A for a total dose of 7500 cGy
- GOG 165: ONE of the following:
- Low-dose rate intracavitary brachytherapy of 4000 cGy to point A given in 1 to 2 fractions
- High-dose rate intracavitary brachytherapy of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
- GOG 165: Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete
References
- GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078
Carboplatin & RT
Carboplatin & RT: Carboplatin & Radiation Therapy
Regimen variant #1, AUC-based carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monk et al. 2023 (CALLA) | 2019-02-15 to 2020-12-10 | Phase 3 (C) | 1a. Carboplatin, Durvalumab, RT 1b. Cisplatin, Durvalumab, RT |
Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 180 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
5-week course
Subsequent treatment
Regimen variant #2, BSA-based carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Veerasarn et al. 2006 | 2001-2003 | Phase 3 (C) | Carboplatin, UFT, RT | Did not meet co-primary endpoints of TTP/OS |
Chemotherapy
- Carboplatin (Paraplatin) 100 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, +/- 36
Radiotherapy
- Concurrent radiation therapy
5- to 6-week course
References
- Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P, Suntornpong N, Sangruchi S, Lertsanguansinchai P, Khorprasert C, Sookpreedee L, Udompunturak S. A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results. Gynecol Oncol. 2007 Jan;104(1):15-23. Epub 2006 Sep 25. link to original article contains dosing details in manuscript PubMed
- CALLA: Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. link to original article contains dosing details in abstract PubMed NCT03830866
Cisplatin & RT
Cisplatin & RT: Cisplatin & Radiation Therapy
Regimen variant #1, weekly cisplatin x 5, no cap + 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kenter et al. 2023 (EORTC-55994) | 2002-05 to 2014-01 | Phase 3 (C) | Neoadjuvant chemotherapy, then surgery | Did not meet primary endpoint of OS60 |
Monk et al. 2023 (CALLA) | 2019-02-15 to 2020-12-10 | Phase 3 (C) | 1a. Carboplatin, Durvalumab, RT 1b. Cisplatin, Durvalumab, RT |
Did not meet primary endpoint of PFS |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 4500 cGy
5-week course
Subsequent treatment
- Sequential brachytherapy (see paper for details)
Regimen variant #2, weekly cisplatin x 5, no cap + 5000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lutgens et al. 2016 (RADCHOC) | 2003-2009 | Phase 3 (C) | RT-HT | Did not meet primary endpoint of EFS |
Shrivastava et al. 2018 (CRACx) | 2003-2011 | Phase 3 (E-esc) | RT | Seems to have superior OS (secondary endpoint) OS60: 54% vs 46% (HR 0.82, 95% CI 0.68-0.98) |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Supportive therapy
- Ondansetron (Zofran) 16 mg (route not specified) once on day 1, prior to cisplatin
- Dexamethasone (Decadron) 8 mg (route not specified) once on day 1, prior to cisplatin
- Pre- and post- cisplatin hydration
Radiotherapy
- Concurrent radiation therapy: 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 5000 cGy
5-week course
Subsequent treatment
- Sequential brachytherapy (see paper for details)
Regimen variant #3, weekly cisplatin x 6, no cap
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pearcey et al. 2002 | 1991-1996 | Phase 3 (E-esc) | RT | Did not meet primary endpoint of OS36 |
Rose et al. 1999 (GOG 120) | 1992-1997 | Phase 3 (E-esc) | 1. Cisplatin, Fluorouracil, Hydroxyurea, RT | Did not meet co-primary endpoints of PFS/OS |
2. Hydroxyurea & RT | Superior OS (co-primary endpoint) | |||
Dueñas-González et al. 2011 (B9E-MC-JHQS) | 2002-2004 | Phase 3 (C) | Cisplatin, Gemcitabine, RT | Seems to have inferior OS |
Sehouli et al. 2012 | 2003-2008 | Phase 3 (C) | Carboplatin & Paclitaxel, then RT | Did not meet primary endpoint of PFS |
Zuliani et al. 2014 | 2003-2010 | Phase 3 (E-esc) | RT | Superior OS1 (co-primary endpoint) (HR 0.53, 95% CI 0.31-0.92) |
DiSilvestro et al. 2014 (GOG 219) | 2006-2009 | Phase 3 (C) | Cisplatin, Tirapazamine, RT | Did not meet primary endpoint of PFS |
Yang et al. 2022 | 2018-2020 | Phase 3 (C) | Nedaplatin & RT | Inferior PFS |
Lorusson et al. 2024 (KEYNOTE-A18) | 2020-06-09 to 2022-12-15 | Phase 3 (C) | Cisplatin, Pembrolizumab, RT | Inferior PFS |
1Reported efficacy is based on the 2020 update.
Note: In GOG 120, this regimen was intended for disease.
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given 1 to 4 hours prior to radiation
Radiotherapy
- Concurrent radiation therapy by the following study-specific criteria:
- GOG 120, stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
- GOG 219: 180 cGy x 23 to 25 fractions, for an initial dose of 41.4 to 4500 cGy
- Pearcey et al. 2002 & Zuliani et al. 2014: 180 cGy x 25 fractions, for an initial dose of 4500 cGy
- B9E-MC-JHQS & Sehouli et al. 2012: 180 cGy x 28 fractions, for an initial dose of 5040 cGy
- GOG 120, stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy
- Yang et al. 2022: 180 cGy/fraction/day, 5 days/week, a total of 25-28 fractions
6-week course, followed in 1 to 3 weeks by:
Subsequent treatment
- Sequential brachytherapy
Regimen variant #4, weekly cisplatin x 6, capped
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Keys et al. 1999 (GOG 123) | 1992-1997 | Phase 3 (E-esc) | RT | Superior OS (co-primary endpoint) OS36: 83% vs 74% (RR 0.54, 95% CI 0.34-0.86) |
Lanciano et al. 2005 (GOG 165) | 1997-2000 | Phase 3 (E-switch-ic) | Fluorouracil & RT | Might have superior ORR (secondary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 (maximum dose of 70 mg) IV once per day on days 1, 8, 15, 22, 29, 36, given 4 hours before radiation
Radiotherapy
- Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Total number of fractions: 25
- Total dose: 4500 cGy
6-week course, followed by:
Subsequent treatment
- GOG 123: Sequential brachytherapy, then adjuvant hysterectomy
- GOG 165: Sequential brachytherapy
Regimen variant #5, q3wk cisplatin x 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ryu et al. 2011 (KCCH GY 1005) | 2002-2004 | Phase 3 (E-switch-ic) | Cisplatin & RT; weekly cisplatin | Superior OS60 OS60: 89% vs 66.5% (HR 0.375, 95% CI 0.15-0.91) |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once per day on days 1, 22, 43
Radiotherapy
- Concurrent radiation therapy: 1.8 to 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, (35 to 37)
- Total number of fractions: 25 to 28
- Total dose: 5000 cGy
9-week course
Subsequent treatment
- Sequential brachytherapy (see paper for details)
References
- GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
- Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
- GOG 123: Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. link to original article contains dosing details in manuscript PubMed
- NCIC-CTG: Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. link to original article contains dosing details in manuscript PubMed
- GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078
- B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100
- KCCH GY 1005: Ryu SY, Lee WM, Kim K, Park SI, Kim BJ, Kim MH, Choi SC, Cho CK, Nam BH, Lee ED. Randomized clinical trial of weekly vs triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e577-81. Epub 2011 Aug 11. link to original article contains dosing details in manuscript PubMed NCT01097252
- Sehouli J, Runnebaum IB, Fotopoulou C, Blohmer U, Belau A, Leber H, Hanker LC, Hartmann W, Richter R, Keyver-Paik MD, Oberhoff C, Heinrich G, du Bois A, Olbrich C, Simon E, Friese K, Kimmig R, Boehmer D, Lichtenegger W, Kuemmel S; NOGGO; AGO. A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Ann Oncol. 2012 Sep;23(9):2259-64. Epub 2012 Feb 21. link to original article contains dosing details in manuscript PubMed
- GOG 219: DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. Epub 2014 Jan 6. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00262821
- Zuliani AC, Esteves SC, Teixeira LC, Teixeira JC, de Souza GA, Sarian LO. Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized controlled trial. J Clin Oncol. 2014 Feb 20;32(6):542-7. Epub 2014 Jan 21. link to original article PubMed
- Update: Fachini AMD, Zuliani AC, Sarian LO, Teixeira JC, Esteves SCB, da Costa Machado H, Zeferino LC. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial. Gynecol Oncol. 2021 Feb;160(2):379-383. Epub 2020 Dec 16. link to original article PubMed
- RADCHOC: Lutgens LC, Koper PC, Jobsen JJ, van der Steen-Banasik EM, Creutzberg CL, van den Berg HA, Ottevanger PB, van Rhoon GC, van Doorn HC, Houben R, van der Zee J. Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial. Radiother Oncol. 2016 Sep;120(3):378-382. Epub 2016 Feb 17. link to original article contains dosing details in abstract PubMed
- CRACx: Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: a randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. link to original article contains dosing details in supplement link to PMC article PubMed NCT00193791
- Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. link to original article link to PMC article contains dosing details in manuscript PubMed ChiCTR1800017108
- EORTC-55994: Kenter GG, Greggi S, Vergote I, Katsaros D, Kobierski J, van Doorn H, Landoni F, van der Velden J, Reed N, Coens C, van Luijk I, Colombo N, Steen-Banasik EV, Ottevanger N, Casado A; EORTC-55994 Study Group. Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994. J Clin Oncol. 2023 Nov 10;41(32):5035-5043. Epub 2023 Sep 1. link to original article PubMed NCT00039338
- CALLA: Monk BJ, Toita T, Wu X, Vázquez Limón JC, Tarnawski R, Mandai M, Shapira-Frommer R, Mahantshetty U, Del Pilar Estevez-Diz M, Zhou Q, Limaye S, Godinez FJR, Oppermann Kussler C, Varga S, Valdiviezo N, Aoki D, Leiva M, Lee JY, Sulay R, Kreynina Y, Cheng WF, Rey F, Rong Y, Ke G, Wildsmith S, Lloyd A, Dry H, Tablante Nunes A, Mayadev J. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1334-1348. link to original article contains dosing details in abstract PubMed NCT03830866
- KEYNOTE-A18: Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. link to original article PubMed NCT04221945
- NRG-GY006: NCT02466971
Cisplatin, Pembrolizumab, RT
Cisplatin, Pembrolizumab, RT: Cisplatin, Pembrolizumab, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lorusson et al. 2024 (KEYNOTE-A18) | 2020-06-09 to 2022-12-15 | Phase 3 (E-RT-esc) | Cisplatin & RT | Superior PFS (co-primary endpoint) PFS24: 68% vs 57% (HR 0.70, 95% CI 0.55-0.89) Did not meet co-primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 & 2: 40 mg/m2 IV once per day on days 1, 8, 15
Radiotherapy
- Concurrent radiation therapy
Immunotherapy
- Pembrolizumab (Keytruda) as follows:
- Cycles 1 to 5: 200 mg IV once on day 1
- Cycles 6 to 20: 400 mg IV once on day 1
21-day cycle for 5 cycles, then 42-day cycle for 15 cycles
References
- KEYNOTE-A18: Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. Epub 2024 Mar 20. link to original article PubMed NCT04221945
Cisplatin & Fluorouracil (CF) & RT
CF & RT: Cisplatin, Fluorouracil Radiation Therapy
Regimen variant #1, 70/4000 x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Whitney et al. 1999 (GOG 85/SWOG 8695) | 1986-1990 | Phase 3 (E-esc) | Hydroxyurea & RT | Seems to have superior OS (co-primary endpoint) Median OS: NYR vs 59.8 mo (RR 0.74, 90% CI 0.58-0.95) |
Peters et al. 2000 (GOG 109/SWOG-8797) | 1991-1996 | Phase 3 (E-esc) | Radiation therapy | Superior OS (co-primary endpoint) OS48: 81% vs 71% (HR 0.51) |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV over 2 hours once per day on days 1, 22, 43, 64
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1, 22, 43, 64 (total dose: 16,000 mg/m2)
Radiotherapy
- Concurrent radiation therapy 170 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 39 (29 fractions, for a total dose of 4930 cGy)
- Patients with positive high common iliac lymph nodes also received 150 cGy x 30 fractions, for a total dose of 4500 cGy
12-week course
Regimen variant #2, 75/4000 x 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morris et al. 1999 (RTOG 9001) | 1990-1997 | Phase 3 (E-esc) | Radiation therapy | Superior OS (primary endpoint) OS60: 73% vs 58% |
Note: radiation could start one day before chemotherapy, on "day 0".
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 4 hours once per day on days 1, 22, 43, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1, 22, 43 (total dose: 12,000 mg/m2)
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
9-week course
Subsequent treatment
- Brachytherapy (see paper for details)
References
- RTOG 9001: Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. link to original article contains dosing details in manuscript PubMed
- GOG 85/SWOG 8695: Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. link to original article PubMed
- GOG 109/SWOG-8797: Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. link to original article contains dosing details in manuscript PubMed
Cisplatin & Fluorouracil (CF) & Hydroxyurea, RT
Cisplatin, Fluorouracil, Hydroxyurea, RT: Cisplatin, Fluorouracil, Hydroxyurea, Radiation Therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rose et al. 1999 (GOG 120) | 1992-1997 | Phase 3 (E-esc) | 1. Cisplatin & RT | Did not meet co-primary endpoints of PFS/OS |
2. Hydroxyurea & RT | Superior OS (co-primary endpoint) |
Definitive therapy
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 & 29
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose per cycle: 4000 mg/m2)
- Hydroxyurea (Hydrea) 2000 mg/m2 PO two times per week, given 2 hours before radiation on weeks 1 to 6
Radiotherapy
- Concurrent radiation therapy by the following stage-based criteria:
- Stage IIB: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 25 (24 fractions, for an initial dose of 4080 cGy)
- Stage III or IVA: 170 cGy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (30 fractions, for an initial dose of 5100 cGy)
5- to 6-week course, followed by:
Consolidation
Radiotherapy
- Stage IIB patients received 4000 cGy by intracavitary brachytherapy, for a total dose of 8080 cGy to point A
- Stage III or IVA disease received 3000 cGy by intracavitary brachytherapy, for a total dose of 8100 cGy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy
One course
References
- GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
- Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
Cisplatin & Gemcitabine (GC) & RT
Cisplatin, Gemcitabine, RT: Cisplatin, Gemcitabine, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dueñas-González et al. 2011 (B9E-MC-JHQS) | 2002-2004 | Phase 3 (E-esc) | Cisplatin & RT | Seems to have superior PFS (primary endpoint) PFS36: 74.4% vs 65% (HR 0.68, 95% CI 0.49-0.95) Seems to have superior OS (secondary endpoint) Median OS: NYR vs NYR (HR 0.68, 95% CI 0.49-0.95) |
Cetina et al. 2013 | 2004-2009 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given first, 1 to 2 hours before radiation
- Gemcitabine (Gemzar) 125 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given second, 1 to 2 hours before radiation
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for an initial dose of 5040 cGy)
6-week course
Subsequent treatment
- B9E-MC-JHQS: Brachytherapy (30 to 3500 cGy delivered to point A), then adjuvant GC, in 2 weeks
- Cetina et al. 2013: Brachytherapy verus radical hysterectomy
References
- B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100
- Cetina L, González-Enciso A, Cantú D, Coronel J, Pérez-Montiel D, Hinojosa J, Serrano A, Rivera L, Poitevin A, Mota A, Trejo E, Montalvo G, Muñoz D, Robles-Flores J, de la Garza J, Chanona J, Jiménez-Lima R, Wegman T, Dueñas-González A. Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients. Ann Oncol. 2013 Aug;24(8):2043-7. Epub 2013 Apr 21. link to original article contains dosing details in abstract PubMed
Fluorouracil & RT
5-FU & RT: 5-FluouroUracil & Radiation Therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lanciano et al. 2005 (GOG 165) | 1997-2000 | Phase 3 (E-switch-ic) | Cisplatin & RT | Might have inferior ORR (secondary endpoint) |
Definitive therapy
Chemotherapy
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29, 36 (total dose: 6750 mg/m2)
Radiotherapy
- Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for an initial dose of 4080 cGy)
6-week course, followed by:
Consolidation
Radiotherapy
- EITHER Low-dose rate intracavitary brachytherapy of 4000 cGy to point A given in 1 to 2 fractions
- OR High-dose rate intracavitary brachytherapy of 3000 cGy to point A given in 5 fractions, starting week 4 of XRT
- Parametrial boost of 5.4 to 900 cGy was administered to the involved parametrium after whole pelvic RT was complete
References
- GOG 165: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. Epub 2005 Oct 17. link to original article contains dosing details in manuscript PubMed NCT00003078
Hydroxyurea & RT
Hydroxyurea & RT: Hydroxyurea & Radiation Therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hreshchyshyn et al. 1979 (GOG 04) | 1970-1976 | Phase 3 (E-esc) | Radiation therapy | Seems to have superior OS |
Stehman et al. 1988 (GOG 56) | 1981-06 to 1985-12 | Randomized | Misonidazole & RT | Seems to have superior PFS1 |
Whitney et al. 1999 (GOG 85/SWOG 8695) | 1986-1990 | Phase 3 (C) | Cisplatin, Fluorouracil, RT | Seems to have inferior OS |
Rose et al. 1999 (GOG 120) | 1992-1997 | Phase 3 (C) | 1. Cisplatin & RT | Inferior OS |
2. Cisplatin, Fluorouracil, Hydroxyurea, RT | Inferior OS |
1Reported efficacy for GOG 56 is based on the 1993 update.
Definitive therapy
Chemotherapy
- Hydroxyurea (Hydrea) as follows:
- Weeks 1 to 6: 2000 mg/m2 PO two times per week, given 2 hours before radiation
Radiotherapy
- Concurrent radiation therapy by the following stage-based criteria:
- Stage IIB: 170 cGy x 24 fractions, for an initial dose of 4080 cGy
- Stage III or IVA: 170 cGy x 30 fractions, for an initial dose of 5100 cGy
7- to 9-week course
Consolidation
Radiotherapy
- Intracavitary brachytherapy by the following stage-based criteria:
- Stage IIB: 4000 cGy for a total dose of 8080 cGy to point A
- Stage III or IVA: 3000 cGy for a total dose of 8100 cGy to point A
- Patients that could not receive brachytherapy underwent additional external beam radiation therapy for a total dose of 6120 cGy
References
- Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA. Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys. 1979 Mar;5(3):317-22. link to original article PubMed
- GOG 56: Stehman FB, Bundy BN, Keys H, Currie JL, Mortel R, Creasman WT. A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix: A preliminary report of a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1988 Jul;159(1):87-94. link to original article PubMed
- Update: Stehman FB, Bundy BN, Thomas G, Keys HM, d'Ablaing G 3rd, Fowler WC Jr, Mortel R, Creasman WT. Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial. J Clin Oncol. 1993 Aug;11(8):1523-8. link to original article PubMed
- GOG 120: Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. link to original article contains dosing details in manuscript PubMed
- Update: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. Epub 2007 May 14. link to original article PubMed
- GOG 85/SWOG 8695: Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. link to original article PubMed
Nedaplatin & RT
Nedaplatin & RT: Nedaplatin & Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2022 | 2018-2020 | Phase 3 (E-switch-ic) | Cisplatin & RT | Superior PFS36 (primary endpoint) Median PFS: 30 vs 28 mo (HR 0.25, 95% CI 0.08-0.77) |
Chemotherapy
- Nedaplatin (Aqupla) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29, +/- 36
Radiotherapy
- Concurrent radiation therapy 180 cGy per day, 5 days/week, a total of 25-28 fractions
References
- Yang X, Ren H, Li Z, Zhang L, Shao Y, Li H, Yang X, Sun Y, Zhang X, Wang Z, Fu J. A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer. ESMO Open. 2022 Oct;7(5):100565. Epub 2022 Aug 19. link to original article link to PMC article contains dosing details in manuscript PubMed ChiCTR1800017108
Adjuvant therapy
Carboplatin & Ifosfamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blohmer et al. 2011 (NOGGO-AGO) | 1999-2001 | Phase 3 (C) | See link | See link |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV over 60 minutes once on day 1
- Ifosfamide (Ifex) 1600 mg/m2 IV over 6 hours once per day on days 1 to 3, with mesa
Supportive therapy
- Mesna (Mesnex) 1600 mg/m2 IV over 6 hours once per day on days 1 to 3, with ifosfamide
21-day cycle for 4 cycles
Subsequent treatment
- Pelvic EBRT x 5040 cGy
References
- NOGGO-AGO: Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article contains dosing details in manuscript PubMed
Cisplatin & Gemcitabine (GC)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Dueñas-González et al. 2011 (B9E-MC-JHQS) | 2002-2004 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Definitive Cisplatin, Gemcitabine, RT
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 2 cycles
References
- B9E-MC-JHQS: Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. Epub 2011 Mar 28. link to original article contains dosing details in manuscript PubMed NCT00191100
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blohmer et al. 2011 (NOGGO-AGO) | 1999-2001 | Phase 3 (C) | See link | See link |
Preceding treatment
- Surgery, then adjuvant Carboplatin & Ifosfamide x 4
Radiotherapy
- External beam radiotherapy: 180 cGy for 28 fractions, for a total dose of 5040 cGy
- If resection margins positive, patients received one of the following:
- EBRT boost of 2 x 500 cGy
- Low-dose brachytherapy
6-week course
References
- NOGGO-AGO: Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P; NOGGO; AGO. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article contains dosing details in manuscript PubMed
Persistent, recurrent, or metastatic disease, first-line therapy
ABCP
ABCP: Atezolizumab, Bevacizumab, Carboplatin, Paclitaxel
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oaknin et al. 2023 (BEATcc) | 2018-10-08 to 2021-08-20 | Phase 3 (E-esc) | 1a. CP & Bevacizumab 1b. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS (co-primary endpoint) Median OS: 32.1 vs 22.8 mo (HR 0.68, 95% CI 0.52-0.88) Superior PFS (co-primary endpoint) Median PFS: 13.7 vs 10.4 mo (HR 0.62, 95% CI 0.49-0.78) |
Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839
Carboplatin monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Weiss et al. 1990 | NR | Phase 2 |
References
- Weiss GR, Green S, Hannigan EV, Boutselis JG, Surwit EA, Wallace DL, Alberts DS; SWOG. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):332-6. link to original article contains dosing details in abstract PubMed
Carboplatin & Docetaxel
Regimen variant #1, 6 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Takekida et al. 2010 | 2004-01 to 2005-12 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron)
- Ondansetron (Zofran) or Granisetron
- Filgrastim (Neupogen) 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia
21-day cycle for up to 6 cycles
Regimen variant #2, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Nagao et al. 2005 | 2001-2004 | Pilot, fewer than 20 pts |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron)
- Ondansetron (Zofran) or Granisetron
- Filgrastim (Neupogen) 5 mcg/kg once per day for patients with grade 4 neutropenia or febrile neutropenia
21-day cycles
References
- Nagao S, Fujiwara K, Oda T, Ishikawa H, Koike H, Tanaka H, Kohno I. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer: a pilot study. Gynecol Oncol. 2005 Mar;96(3):805-9. link to original article contains dosing details in manuscript PubMed
- Takekida S, Fujiwara K, Nagao S, Yamaguchi S, Yoshida N, Kitada F, Kigawa J, Terakawa N, Nishimura R. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer. 2010 Dec;20(9):1563-8. link to original article PubMed
Carboplatin & Paclitaxel (CP)
TC: Taxol (Paclitaxel) & Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pectasides et al. 2009a | NR | Phase 2 | ||
Kitagawa et al. 2015 (JCOG0505) | 2006-2009 | Phase 3 (E-switch-ic) | Cisplatin & Paclitaxel | Non-inferior OS (primary endpoint) Median OS: 17.5 vs 18.3 mo (HR 0.994, 90% CI 0.79-1.25) |
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
Note: Pectasides et al. 2009a allowed the regimen to be given up to 9 cycles. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for 6 or more cycles (see note)
References
- Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. link to original article contains dosing details in abstract PubMed
- JCOG0505: Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00295789
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Carboplatin & Paclitaxel (CP) & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
Oaknin et al. 2023 (BEATcc) | 2018-10-08 to 2021-08-20 | Phase 3 (C) | 1a. ABCP 1b. Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab |
Inferior PFS/OS |
Note: In KEYNOTE-826, the decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
- BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839
Carboplatin & Paclitaxel (CP), Bevacizumab, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77) |
1Reported efficacy is based on the 2023 update for all patients.
Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) as follows:
- Cycles 1 up to 35: 200 mg IV once on day 1
21-day cycles
References
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Carboplatin & Paclitaxel (CP) & Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77) |
1Reported efficacy is based on the 2023 update for all patients.
Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6 (see note): AUC 5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Cisplatin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thigpen et al. 1979a | NR in abstract | Phase 2 | ||
Bonomi et al. 1985 (GOG 43) | 1978-1982 | Phase 3 (C) | 1. Cisplatin; higher dose 2. Cisplatin; higher dose, split doses |
Did not meet primary endpoint of ORR |
Thigpen et al. 1989 (GOG 64) | 1982-1985 | Phase 3 (C) | Cisplatin; CI | Did not meet primary efficacy endpoints |
Omura et al. 1997 (GOG 110) | 1990-1994 | Phase 3 (C) | 1. Cisplatin & Ifosfamide | Inferior PFS |
2. Cisplatin & Mitolactol | Did not meet primary endpoint of ORR | |||
Vermorken et al. 2001 | 1986-1991 | Phase 3 (C) | BEMP | Did not meet primary endpoint of ORR |
Moore et al. 2004 (GOG 169) | 1997-1999 | Phase 3 (C) | Cisplatin & Paclitaxel | Inferior PFS |
Long et al. 2005 (GOG 179) | 1999-2002 | Phase 3 (C) | 1. Cisplatin & Topotecan | Seems to have inferior OS |
2. MVAC | Not reported | |||
Aoki et al. 2018 (Taiho 10020380) | 2008-2011 | Phase 3 (C) | Cisplatin & S-1 | Did not meet primary endpoint of OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
21-day cycles; if not responding, given for maximum of 6 cycles
References
- Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J; Gynecologic Oncology Group. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1549-55. PubMed
- GOG 43: Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major FJ. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Aug;3(8):1079-85. link to original article PubMed
- GOG 64: Thigpen JT, Blessing JA, DiSaia PJ, Fowler WC Jr, Hatch KD. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1989 Feb;32(2):198-202. link to original article contains dosing details in abstract PubMed
- GOG 110: Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. link to original article contains dosing details in abstract PubMed
- Vermorken JB, Zanetta G, Freire de Oliveira C, van der Burg ME, Lacave AJ, Teodorovic I, Boes GH, Colombo N; EORTC Gynecological Cancer Cooperative Group. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol. 2001 Jul;12(7):967-74. link to original article PubMed
- GOG 169: Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains dosing details in manuscript PubMed
- GOG 179: Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains dosing details in manuscript PubMed NCT00003945
- Taiho 10020380: Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, Katsumata N, Cha SD, Kim JH, Kim BG, Hirashima Y, Fujiwara K, Kim YT, Kim SM, Chung HH, Chang TC, Kamura T, Takizawa K, Takeuchi M, Kang SB. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer. 2018 Aug;119(5):530-537. Epub 2018 Aug 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00770874
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine, Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monk et al. 2009 (GOG 204) | 2003-2007 | Phase 3 (E-switch-ic) | 1. Cisplatin & Paclitaxel | Seems to have inferior PFS (secondary endpoint) |
2. Cisplatin & Topotecan | Did not meet primary endpoint of OS | |||
3. Cisplatin & Vinorelbine | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
Cisplatin & Ifosfamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Omura et al. 1997 (GOG 110) | 1990-1994 | Phase 3 (E-esc) | 1. Cisplatin | Superior PFS (secondary endpoint) |
2. Cisplatin & Mitolactol | Not reported | |||
Bloss et al. 2002 (GOG 149) | 1994-1997 | Phase 3 (C) | CIB | Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 1 concurrent with mesna
Supportive therapy
- Mesna (Mesnex) 6000 mg/m2 IV continuous infusion over 36 hours, started on day 1 concurrent with ifosfamide
21-day cycle for up to 6 cycles
References
- GOG 110: Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. link to original article contains dosing details in abstract PubMed
- GOG 149: Bloss JD, Blessing JA, Behrens BC, Mannel RS, Rader JS, Sood AK, Markman M, Benda J. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2002 Apr 1;20(7):1832-7. link to original article PubMed
Cisplatin & Mitomycin
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Wagenaar et al. 2001 | NR | Phase 2 | ORR: 42% (95% CI: 26-61%) |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1, given second
- Mitomycin (Mutamycin) 6 mg/m2 IV push once on day 1, given first
Supportive therapy
- 1 liter NS over 1 hour once on day 1, prior to chemotherapy, then 1 liter NS over 1 hour once on day 1, after cisplatin
- Furosemide (Lasix) (route/dose not specified) once on day 1, prior to chemotherapy
- Mannitol IV push once on day 1, prior to cisplatin
28-day cycle for 9 cycles
References
- Wagenaar HC, Pecorelli S, Mangioni C, van der Burg ME, Rotmensz N, Anastasopoulou A, Zola P, Veenhof CH, Lacave AJ, Neijt JP, van Oosterom AT, Einhorn N, Vermorken JB; EORTC Gynecological Cancer Group. Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix: a European Organisation for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer. 2001 Sep;37(13):1624-8. link to original article contains dosing details in manuscript PubMed
Cisplatin & Paclitaxel
PC: Paclitaxel & Cisplatin
CP: Cisplatin & Paclitaxel
TP: Taxol (Paclitaxel) & Platinol (Cisplatin)
Regimen variant #1, 50/135, 3 hr paclitaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (C) | 1. Cisplatin, Paclitaxel, Bevacizumab | Inferior OS1 |
2. Paclitaxel & Topotecan | Did not meet primary endpoint of OS | |||
3. Paclitaxel, Topotecan, Bevacizumab | Not reported |
1Reported efficacy is based on the 2017 update.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 135 mg/m2 IV once on day 1
21-day cycles until CR or indefinitely
Regimen variant #2, 50/135, CI paclitaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moore et al. 2004 (GOG 169) | 1997-1999 | Phase 3 (E-esc) | Cisplatin | Superior PFS (secondary endpoint) Superior ORR (primary endpoint) |
Monk et al. 2009 (GOG 204) | 2003-2007 | Phase 3 (C) | 1. Cisplatin & Gemcitabine | Seems to have superior PFS (secondary endpoint) |
2. Cisplatin & Topotecan | Did not meet primary endpoint of OS | |||
3. Cisplatin & Vinorelbine | Might have superior PFS (secondary endpoint) | |||
Kitagawa et al. 2015 (JCOG0505) | 2006-2009 | Phase 3 (C) | Carboplatin & Paclitaxel | Non-inferior OS |
Note: patients in JCOG0505 received a maximum of 6 cycles.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 2
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive therapy
- (varies depending on reference):
- Dexamethasone (Decadron)
- Diphenhydramine (Benadryl)
- H2 receptor antagonist such as Cimetidine (Tagamet) or Ranitidine (Zantac)
- Prophylactic antiemetics
- "Adequate IV hydration and electrolyte replacement"
21-day cycles; if not responding, given for maximum of 6 cycles.
Regimen variant #3, 50/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (C) | 1. Cisplatin, Paclitaxel, Bevacizumab | Inferior OS1 |
2. Paclitaxel & Topotecan | Did not meet primary endpoint of OS | |||
3. Paclitaxel, Topotecan, Bevacizumab | Not reported | |||
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
1Reported efficacy is based on the 2017 update.
Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 6 or more cycles (see note)
References
- GOG 169: Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. link to original article contains dosing details in manuscript PubMed
- GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
- GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
- Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
- Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed
- JCOG0505: Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00295789
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Cisplatin, Paclitaxel, Bevacizumab
CP+Bev: Cisplatin, Paclitaxel, Bevacizumab
ESMO-preferred (I-A, 2017) |
Regimen variant #1, 135 mg/m2 paclitaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (E-RT-esc) | 1. Cisplatin & Paclitaxel | Superior OS1 (primary endpoint) Median OS: 16.8 vs 13.3 mo (HR 0.77, 95% CI 0.62-0.95) |
2. Paclitaxel & Topotecan | Did not meet primary endpoint of OS1 | |||
3. Paclitaxel, Topotecan, Bevacizumab | Not reported |
1Reported efficacy is based on the 2017 update.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 135 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles until CR or indefinitely
Regimen variant #2, 175 mg/m2 paclitaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (E-RT-esc) | 1. Cisplatin & Paclitaxel | Superior OS1 (primary endpoint) Median OS: 16.8 vs 13.3 mo (HR 0.77, 95% CI 0.62-0.95) |
2. Paclitaxel & Topotecan | Did not meet primary endpoint of OS1 | |||
3. Paclitaxel, Topotecan, Bevacizumab | Not reported | |||
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (C) | 1a. CP & Pembrolizumab 1b. CP, Bevacizumab, Pembrolizumab 1c. Cisplatin, Paclitaxel, Pembrolizumab 1d. Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab |
Inferior OS |
Oaknin et al. 2023 (BEATcc) | 2018-10-08 to 2021-08-20 | Phase 3 (C) | 1a. ABCP 1b. Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab |
Inferior PFS/OS |
1Reported efficacy for this comparison in GOG 240 is based on the 2017 update.
Note: Treatment in GOG 240 was given until CR or indefinitely. Patients in KEYNOTE-826 were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects. Patients in BEATcc with a complete response after at least six cycles could discontinue chemotherapy and continue bevacizumab maintenance. The decision to give bevacizumab in KEYNOTE-826 was at the discretion of the treating institution and was not a randomization.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 6 or more cycles (see note)
References
- GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
- Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
- Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
- BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839
Cisplatin, Paclitaxel, Atezolizumab, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oaknin et al. 2023 (BEATcc) | 2018-10-08 to 2021-08-20 | Phase 3 (E-esc) | 1a. CP & Bevacizumab 1b. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS (co-primary endpoint) Median OS: 32.1 vs 22.8 mo (HR 0.68, 95% CI 0.52-0.88) Superior PFS (co-primary endpoint) Median PFS: 13.7 vs 10.4 mo (HR 0.62, 95% CI 0.49-0.78) |
Note: Patients with a complete response after at least six cycles could discontinue chemotherapy and continue atezolizumab & bevacizumab maintenance.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- BEATcc: Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. Epub 2023 Dec 1. link to original article contains dosing details in manuscript PubMed NCT03556839
Cisplatin, Paclitaxel, Bevacizumab, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77) |
1Reported efficacy is based on the 2023 update for all patients.
Note: The decision to give bevacizumab was at the discretion of the treating institution and was not a randomization. Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 6 (see note): 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) as follows:
- Cycles 1 up to 35: 200 mg IV once on day 1
21-day cycles
References
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Cisplatin, Paclitaxel, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2021 (KEYNOTE-826) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CP 1b. CP & Bevacizumab 1c. Cisplatin & Paclitaxel 1d. Cisplatin, Paclitaxel, Bevacizumab |
Superior OS1 (co-primary endpoint) Median OS: 26.4 vs 16.8 mo (HR 0.63, 95% CI 0.52-0.77) |
1Reported efficacy is based on the 2023 update for all patients.
Note: Patients were permitted to receive more than 6 cycles of chemotherapy if they had ongoing clinical benefit and did not have unacceptable side effects.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 6 (see note): 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6 (see note): 175 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-826: Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. Epub 2021 Sep 18. link to original article contains dosing details in manuscript PubMed NCT03635567
- HRQoL analysis: Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. Epub 2023 Mar 3. link to original article PubMed
- Update: Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. Epub 2023 Nov 1. link to original article PubMed
Cisplatin & Topotecan
TC: Topotecan & Cisplatin
CT: Cisplatin & Topotecan
Regimen variant #1, 6 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Long et al. 2005 (GOG 179) | 1999-2002 | Phase 3 (E-RT-esc) | 1. Cisplatin | Seems to have superior OS (primary endpoint) Median OS: 9.4 vs 6.5 mo (RR 0.76, 95% CI 0.59-0.98) |
2. MVAC | Not reported | |||
Monk et al. 2009 (GOG 204) | 2003-2007 | Phase 3 (E-switch-ic) | 1. Cisplatin & Gemcitabine | Did not meet primary endpoint of OS |
2. Cisplatin & Paclitaxel | Did not meet primary endpoint of OS | |||
3. Cisplatin & Vinorelbine | Did not meet primary endpoint of OS | |||
Coronel et al. 2010 (006/027/ICI) | 2007-2009 | Phase 3 (C) | CT + HV | Seems to have inferior PFS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1, given second
- Topotecan (Hycamtin) 0.75 mg/m2 IV over 30 minutes once per day on days 1 to 3, given first
21-day cycle for up to 6 cycles
Regimen variant #2, 6 to 9 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gass et al. 2024 (AGO-Zervix-1) | 2007-01 to 2012-06 | Phase 3 (C) | TP | Did not meet primary endpoint of OS Median OS: 12 vs 9.6 mo |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1, given second
- Topotecan (Hycamtin) 0.75 mg/m2 IV over 30 minutes once per day on days 1 to 3, given first
21-day cycle for 6 up to 9 cycles
References
- GOG 179: Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. Epub 2005 May 23. link to original article contains dosing details in manuscript PubMed NCT00003945
- GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
- 006/027/ICI: Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M, Vidal S, Dueñas-González A. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer: preliminary results. Med Oncol. 2011 Dec;28 Suppl 1:S540-6. Epub 2010 Oct 8. link to original article contains dosing details in manuscript PubMed NCT00532818
- AGO-Zervix-1: Gass P, Thiel FC, Häberle L, Ackermann S, Theuser AK, Hummel N, Boehm S, Kimmig R, Reinthaller A, Becker S, Hilpert F, Janni W, Vergote I, Harter P, Emons J, Hein A, Beckmann MW, Fasching PA, Pöschke P; AGO Uterus Commission. Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer. Gynecol Oncol. 2024 Apr;183:25-32. Epub 2024 Mar 14. link to original article contains dosing details in manuscript PubMed NCT01405235
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
VC: Vinorelbine, Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monk et al. 2009 (GOG 204) | 2003-2007 | Phase 3 (E-switch-ic) | 1. Cisplatin & Gemcitabine | Did not meet primary endpoint of OS |
2. Cisplatin & Paclitaxel | Might have inferior PFS (primary endpoint) | |||
3. Cisplatin & Topotecan | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles; if not responding, given for maximum of 6 cycles
References
- GOG 204: Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. Epub 2009 Aug 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00064077
Ifosfamide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Coleman et al. 1986 | NR | Phase 2 |
Sutton et al. 1993b | 1985-07 to 1990-12 | Phase 2 |
Sutton et al. 1993a | 1988-01 to 1990-02 | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) by the following exposure-based criteria:
- No previous pelvic radiation or other chemotherapy: 1500 mg/m2 IV once per day on days 1 to 5
- Previous pelvic radiation or other chemotherapy: 1200 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) at 20% of ifosfamide dose (for example, 300 mg/m2 for 1500 mg/m2 dose of ifosfamide) IV given at 0, 4, and 8 hours after each dose of ifosfamide on days 1 to 5
21-day cycles
Dose and schedule modifications
- Ifosfamide (Ifex) dose could be increased by 300 mg/m2 or decreased by 20% depending on toxicity
References
- Coleman RE, Harper PG, Gallagher C, Osborne R, Rankin EM, Silverstone AC, Slevin ML, Souhami RL, Tobias JS, Trask CW, Wiltshaw E. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986;18(3):280-3. link to original article PubMed
- Sutton GP, Blessing JA, McGuire WP, Patton T, Look KY; Gynecologic Oncology Group. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):805-7. link to original article PubMed
- Sutton GP, Blessing JA, DiSaia PJ, McGuire WP; Gynecologic Oncology Group. Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1993 Apr;49(1):48-50. link to original article contains dosing details in manuscript PubMed
Paclitaxel monotherapy
Regimen variant #1, 135 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
McGuire et al. 1996 | 1990 | Phase 2 |
Curtin et al. 2001 | 1994 | Phase 2 |
Note: this was the dosage used for patients with previous pelvic radiation.
Chemotherapy
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycles
Dose and schedule modifications
- Paclitaxel (Taxol) dose could be changed to 110 or 200 mg/m2 depending on toxicity
Regimen variant #2, 170 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
McGuire et al. 1996 | 1990 | Phase 2 |
Curtin et al. 2001 | 1994 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) by the following exposure-based criteria:
- No previous pelvic radiation: 170 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Previous pelvic radiation: 135 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 14 and 7 hours prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycles
Dose and schedule modifications
- Paclitaxel (Taxol) dose could be changed to 110 or 200 mg/m2 depending on toxicity
Regimen variant #3, 250 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Kudelka et al. 1996 | NR | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 250 mg/m2 IV over 3 hours once on day 1
Supportive therapy
- Dexamethasone (Decadron) 20 mg PO for two doses on day 1; 14 and 7 hours prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to paclitaxel
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 2, 24 hours after paclitaxel, given until day 19 or until ANC greater or equal to 10,000/μL
21-day cycles
Dose and schedule modifications
- Paclitaxel (Taxol) dose could be changed to 275, 225, or 200 mg/m2 depending on toxicity
References
- McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G; Gynecologic Oncology Group. Paclitaxel has moderate activity in squamous cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1996 Mar;14(3):792-5. link to original article contains dosing details in manuscript PubMed
- Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, Loyer E, Rusinkiewicz J, Gacrama P, Fueger R, Kavanagh JJ. Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res. 1996 Aug;2(8):1285-8. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
- Update: Kudelka AP, Winn R, Edwards CL, Downey G, Greenberg H, Dakhil SR, Freedman RS, LoCoco S, Umbreit J, Delmore JE, Arbuck S, Loyer E, Gacrama P, Fueger R, Kavanagh JJ. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs. 1997 Aug;8(7):657-61. link to original article PubMed
- Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC Jr, Malfetano JH, Alvarez RD; Gynecologic Oncology Group. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Mar 1;19(5):1275-8. link to original article contains dosing details in manuscript PubMed
Paclitaxel, Topotecan, Bevacizumab
TP+Bev: Topotecan, Paclitaxel, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2014 (GOG 240) | 2009-2012 | Phase 3 (E-RT-esc) | 1. Cisplatin & Paclitaxel | Not reported |
2. Cisplatin, Paclitaxel, Bevacizumab | Not reported | |||
3. Paclitaxel & Topotecan | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2017 update.
Note: in the initial report, topotecan & paclitaxel +/- bevacizumab regimens were "associated with a significantly higher risk of progression" as compared to cisplatin & paclitaxel +/- bevacizumab regimens.
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
- Topotecan (Hycamtin) 0.75 mg/m2 IV once per day on days 1 to 3
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- GOG 240: Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. link to original article link to supplementary appendix contains dosing details in manuscript link to PMC article PubMed NCT00803062
- Update: Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, DiSaia PJ, Copeland LJ, Creasman WT, Stehman FB, Brady MF, Burger RA, Thigpen JT, Birrer MJ, Waggoner SE, Moore DH, Look KY, Koh WJ, Monk BJ. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017 Oct 7;390(10103):1654-1663. Epub 2017 Jul 27. link to original article link to PMC article PubMed
- Update: Tewari KS, Sill MW, Birrer MJ, Penson RT, Huang H, Moore DH, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. Gynecol Oncol. 2023 Apr;171:141-150. Epub 2023 Mar 8. link to original article PubMed
Topotecan monotherapy
Regimen variant #1, q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Bookman et al. 2000 (GOG 127-F) | 1994-12 to NR | Phase 2 |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycles
Regimen variant #2, q4wk
Study | Dates of enrollment | Evidence |
---|---|---|
Muderspach et al. 2001 (GOG 76-U) | 1994-01 to 1995-12 | Phase 2 |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
28-day cycles
References
- Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA; Gynecologic Oncology Group. Topotecan in squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9. link to original article contains dosing details in manuscript PubMed
- GOG 76-U: Muderspach LI, Blessing JA, Levenback C, Moore JL Jr; Gynecologic Oncology Group. A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Gxroup study. Gynecol Oncol. 2001 May;81(2):213-5. link to original article contains dosing details in manuscript PubMed
Vinorelbine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Morris et al. 1998 | 1993-1995 | Phase 2 | ORR: 18% |
References
- Morris M, Brader KR, Levenback C, Burke TW, Atkinson EN, Scott WR, Gershenson DM. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998 Mar;16(3):1094-8. link to original article contains dosing details in manuscript PubMed
Advanced or metastatic disease, subsequent lines of therapy
Bevacizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Monk et al. 2009 (GOG 227-C) | 2002-2006 | Phase 2 |
References
- Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD; Gynecologic Oncology Group. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. Epub 2009 Jan 12. link to original article contains dosing details in manuscript link to PMC article PubMed
Cemiplimab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (E-switch-ooc) | 1a. Pemetrexed 1b. Topotecan 1c. Irinotecan 1d. Gemcitabine 1e. Vinorelbine |
Superior OS (primary endpoint) Median OS: 12 vs 8.5 mo (HR 0.69, 95% CI 0.56-0.84) |
Immunotherapy
- Cemiplimab (Libtayo) 350 mg IV once on day 1
21-day cycle for up to 32 cycles (96 weeks)
References
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine, Cisplatin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Brewer et al. 2006 | 2001-2002 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once on day 1, given first
- Gemcitabine (Gemzar) 800 mg/m2 IV once per day on days 1 & 8, given second
28-day cycles
References
- Brewer CA, Blessing JA, Nagourney RA, McMeekin DS, Lele S, Zweizig SL; Gynecologic Oncology Group. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006 Feb;100(2):385-8. Epub 2005 Nov 4. link to original article contains dosing details in manuscript PubMed
Docetaxel monotherapy
Regimen variant #1, 36 mg/m2, 3 weeks out of 4
Study | Dates of enrollment | Evidence |
---|---|---|
Garcia et al. 2008 | 2004-07 to 2005-04 | Phase 2 |
Chemotherapy
- Docetaxel (Taxotere) 36 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO the evening before, morning of, and evening of each dose of docetaxel
28-day cycles
Regimen variant #2, 100 mg/m2, q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Garcia et al. 2007 | 2002-06 to 2004-12 | Phase 2 |
References
- Garcia AA, Blessing JA, Vaccarello L, Roman LD; Gynecologic Oncology Group. Phase II clinical trial of docetaxel in refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 2007 Aug;30(4):428-31. link to original article contains dosing details in abstract PubMed
- Garcia AA, Blessing JA, Nolte S, Mannel RS; Gynecologic Oncology Group. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008 Oct;111(1):22-6. link to original article contains dosing details in manuscript PubMed
FULV
FULV: 5-FU & LeucoVorin
Regimen variant #1, 1850/200
Study | Dates of enrollment | Evidence |
---|---|---|
Look et al. 1996 | 1990-1992 | Phase 2 |
Look et al. 1997 | 1993-1995 | Phase 2 |
Note: it is not entirely clear from these publications whether leucovorin is given on day 1 only, versus on days 1 to 5.
Chemotherapy
- Fluorouracil (5-FU) 370 mg/m2 IV over 5 minutes once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 200 mg/m2 IV bolus once on day 1 (see note), given first
28-day cycle for 2 cycles, then 35-day cycles
Regimen variant #2, 2125/100
Study | Dates of enrollment | Evidence |
---|---|---|
Look et al. 1992 | 1989-09 to 1990-04 | Phase 2 |
Chemotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5, given first
28-day cycle for 2 cycles, then 35-day cycles
References
- Look KY, Blessing JA, Muss HB, Partridge EE, Malfetano JH; Gynecologic Oncology Group. 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol. 1992 Dec;15(6):497-9. link to original article PubMed
- Look KY, Blessing JA, Gallup DG, Lentz SS; Gynecologic Oncology Group. A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Clin Oncol. 1996 Oct;19(5):439-41. link to original article contains dosing details in manuscript PubMed
- Look KY, Blessing JA, Valea FA, McGehee R, Manetta A, Webster KD, Andersen WA; Gynecologic Oncology Group. Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1997 Dec;67(3):255-8. link to original article contains dosing details in manuscript PubMed
Gemcitabine monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Schilder et al. 2000 (GOG 127-K) | NR | Phase 2 |
Schilder et al. 2005 | NR | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
References
- GOG 127-K: Schilder RJ, Blessing JA, Morgan M, Mangan CE, Rader JS; Gynecologic Oncology Group. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Feb;76(2):204-7. link to original article contains dosing details in manuscript PubMed
- Schilder RJ, Blessing J, Cohn DE; Gynecologic Oncology Group. Evaluation of gemcitabine in previously treated patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2005 Jan;96(1):103-7. link to original article contains dosing details in manuscript PubMed
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
- innovaTV 301: NCT04697628
Irinotecan monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verschraegen et al. 1997 | 1993-1995 | Phase 2 | ||
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
Supportive therapy
- Diphenhydramine (Benadryl) 25 to 50 mg IV or PO every 6 hours as needed for diarrhea during irinotecan infusion
- Atropine (Atropen) 1 mg IV every 6 hours as needed for diarrhea during irinotecan infusion
- Loperamide (Imodium) 4 mg PO as needed for each episode of delayed diarrhea between irinotecan infusions
42-day cycles
References
- Verschraegen CF, Levy T, Kudelka AP, Llerena E, Ende K, Freedman RS, Edwards CL, Hord M, Steger M, Kaplan AL, Kieback D, Fishman A, Kavanagh JJ. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol. 1997 Feb;15(2):625-31. link to original article contains dosing details in manuscript PubMed
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
- innovaTV 301: NCT04697628
Pembrolizumab monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Chung et al. 2019 (KEYNOTE-158cervical) | 2016-01-27 to 2016-08-18 | Phase 2 (RT) |
Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-158cervical: Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Epub 2019 Apr 3. link to original article contains dosing details in abstract PubMed NCT02628067
Pemetrexed monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Miller et al. 2008 | 2004-2006 | Phase 2 |
Chemotherapy
- Pemetrexed (Alimta) 900 mg/m2 IV over 10 minutes once on day 1
Supportive therapy
- Folic acid (Folate) 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
21-day cycles
References
- Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO; Gynecologic Oncology Group. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2008 Jul;110(1):65-70. Epub 2008 May 5. link to original article contains dosing details in manuscript PubMed
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
- innovaTV 301: NCT04697628
Tisotumab vedotin monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coleman et al. 2021 (innovaTV 204) | 2018-06-12 to 2019-04-11 | Phase 2 (RT) | ||
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (E-RT-switch-ooc) | 1a. Pemetrexed 1b. Topotecan 1c. Irinotecan 1d. Gemcitabine 1e. Vinorelbine |
Superior OS (primary endpoint) Median OS: 11.5 vs 9.5 mo (HR 0.70, 95% CI 0.54-0.89) |
Antibody-drug conjugate therapy
- Tisotumab vedotin (Tivdak) 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1
21-day cycles
References
- innovaTV 204: Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. Epub 2021 Apr 9. link to original article contains dosing details in abstract PubMed NCT03438396
- innovaTV 301: NCT04697628
Topotecan monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Dosing information is from CT.gov.
References
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
- innovaTV 301: NCT04697628
Vinorelbine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Muggia et al. 2004 | 1997-1999 | Phase 2 | ORR: 14% (95% CI 5-27%) | |
Muggia et al. 2005 | 1997-1999 | Phase 2 | ORR: 7% | |
Tewari et al. 2022 (EMPOWER-Cervical 1) | 2017-2020 | Phase 3 (C) | Cemiplimab | Inferior OS |
Awaiting publication (innovaTV 301) | 2021-2023 | Phase 3 (C) | Tisotumab vedotin | Inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
References
- Muggia FM, Blessing JA, Method M, Miller DS, Johnson GA, Lee RB, Menzin A; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Feb;92(2):639-43. link to original article contains dosing details in manuscript PubMed
- Muggia FM, Blessing JA, Waggoner S, Berek JS, Monk BJ, Sorosky J, Pearl ML; Gynecologic Oncology Group. Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Jan;96(1):108-11. link to original article contains dosing details in manuscript PubMed
- EMPOWER-Cervical 1: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. link to original article contains dosing details in manuscript PubMed NCT03257267
- innovaTV 301: NCT04697628