Difference between revisions of "Ovarian cancer - historical"
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− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | <span id="BackToTop"></span> |
− | + | <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> | ||
+ | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Ovarian_cancer|main ovarian cancer page]] for current regimens. | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | ||
|} | |} | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Adjuvant chemotherapy for early stage disease= | =Adjuvant chemotherapy for early stage disease= | ||
==Cisplatin & Cyclophosphamide {{#subobject:94237c|Regimen=1}}== | ==Cisplatin & Cyclophosphamide {{#subobject:94237c|Regimen=1}}== | ||
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CP: '''<u>C</u>'''yclophosphamide & '''<u>P</u>'''latinol (Cisplatin) | CP: '''<u>C</u>'''yclophosphamide & '''<u>P</u>'''latinol (Cisplatin) | ||
<br>PC: '''<u>P</u>'''latinol (Cisplatin) & '''<u>C</u>'''yclophosphamide | <br>PC: '''<u>P</u>'''latinol (Cisplatin) & '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:339a27|Variant=1}}=== | ===Regimen {{#subobject:339a27|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 26: | Line 25: | ||
|[https://doi.org/10.1200/JCO.2003.02.154 Young et al. 2003 (GOG 95)] | |[https://doi.org/10.1200/JCO.2003.02.154 Young et al. 2003 (GOG 95)] | ||
|1986-1994 | |1986-1994 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |IP P32 | + | |[[#Radioactive_chromic_phosphate_monotherapy_999|IP P32]] |
| 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:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[Surgery#Ovarian_cancer_surgery|Surgery]] | *[[Surgery#Ovarian_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GOG 95:''' Young RC, Brady MF, Nieberg RK, Long HJ, Mayer AR, Lentz SS, Hurteau J, Alberts DS. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a Gynecologic Oncology Group study. J Clin Oncol. 2003 Dec 1;21(23):4350-5. [https://doi.org/10.1200/JCO.2003.02.154 link to original article] '''contains | + | # '''GOG 95:''' Young RC, Brady MF, Nieberg RK, Long HJ, Mayer AR, Lentz SS, Hurteau J, Alberts DS. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a Gynecologic Oncology Group study. J Clin Oncol. 2003 Dec 1;21(23):4350-5. [https://doi.org/10.1200/JCO.2003.02.154 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14645424/ PubMed] |
− | |||
==Melphalan monotherapy {{#subobject:d10939|Regimen=1}}== | ==Melphalan monotherapy {{#subobject:d10939|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
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===Regimen {{#subobject:ab1d2c|Variant=1}}=== | ===Regimen {{#subobject:ab1d2c|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 57: | Line 54: | ||
|[https://doi.org/10.1200/JCO.1988.6.8.1254 Klaassen et al. 1988] | |[https://doi.org/10.1200/JCO.1988.6.8.1254 Klaassen et al. 1988] | ||
|1975-1984 | |1975-1984 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
− | |WAI | + | |[[#Radiation_therapy_888|WAI]] |
| style="background-color:#91cf60" |Seems to have superior DFS | | style="background-color:#91cf60" |Seems to have superior DFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] 8 mg/m<sup>2</sup> PO once per day on days 1 to 4 |
− | + | '''28-day cycle for 18 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Klaassen D, Shelley W, Starreveld A, Kirk M, Boyes D, Gerulath A, Levitt M, Fraser R, Carmichael J, Methot Y, Willan A; National Cancer Institute of Canada Clinical Trials Group. Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report. J Clin Oncol. 1988 Aug;6(8):1254-63. [https://doi.org/10.1200/JCO.1988.6.8.1254 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3045264 PubMed] | + | # Klaassen D, Shelley W, Starreveld A, Kirk M, Boyes D, Gerulath A, Levitt M, Fraser R, Carmichael J, Methot Y, Willan A; National Cancer Institute of Canada Clinical Trials Group. Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report. J Clin Oncol. 1988 Aug;6(8):1254-63. [https://doi.org/10.1200/JCO.1988.6.8.1254 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3045264/ PubMed] |
=First-line chemotherapy for advanced stage disease= | =First-line chemotherapy for advanced stage disease= | ||
''Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.'' | ''Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.'' | ||
− | == | + | ==Altretamine & Cisplatin (HD) {{#subobject:d0uyq9|Regimen=1}}== |
− | {| class="wikitable" style=" | + | HD: '''<u>H</u>'''examethylmelamine (Altretamine) & '''<u>D</u>'''DP (Cisplatin) |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #1 {{#subobject:697yjc|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/10.3109/07357909209032783 Wiernik et al. 1992a] | ||
+ | |1979-1985 | ||
+ | |style="background-color:#1a9851"|Randomized (E-RT-de-esc) | ||
+ | |[[#Altretamine.2C_Cisplatin.2C_Pyridoxine_888|Altretamine, Cisplatin, Pyridoxine]] | ||
+ | |style="background-color:#d3d3d3"|Not clearly reported | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | + | *[[Altretamine (Hexalen)]] 200 mg/m<sup>2</sup> PO once per day on days 8 to 21 | |
− | ===Regimen {{#subobject: | + | *[[Cisplatin (Platinol)]] 37.5 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2 {{#subobject:757yjc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| 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: | + | !style="width: 20%"|Comparator |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |||
|- | |- | ||
− | + | |[https://doi.org/10.3109/07357909209032783 Wiernik et al. 1992a] | |
− | + | |1979-1985 | |
− | + | |style="background-color:#1a9851"|Randomized (E-RT-de-esc) | |
− | + | |[[#Altretamine.2C_Cisplatin.2C_Pyridoxine_888|Altretamine, Cisplatin, Pyridoxine]] | |
− | + | |style="background-color:#d3d3d3"|Not clearly reported | |
− | |||
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− | |[https://doi.org/10. | ||
− | | | ||
− | |style="background-color:#1a9851"| | ||
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− | |[[# | ||
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− | | style="background-color:# | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Altretamine (Hexalen)]] 200 mg/m<sup>2</sup> PO once per day on days 8 to 21 |
− | + | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[Cisplatin (Platinol)]] | + | '''21-day cycles''' |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # Wiernik PH, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J; [[Study_Groups#ECOG|ECOG]]. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992;10(1):1-9. [https://doi.org/10.3109/07357909209032783 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1735009/ PubMed] |
− | |||
− | # | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==Carboplatin & Cyclophosphamide {{#subobject:d48754|Regimen=1}}== | ==Carboplatin & Cyclophosphamide {{#subobject:d48754|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e87g77|Variant=1}}=== | ===Regimen {{#subobject:e87g77|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 178: | Line 129: | ||
|[https://doi.org/10.1200/JCO.1992.10.5.706 Alberts et al. 1992 (SWOG 8412)] | |[https://doi.org/10.1200/JCO.1992.10.5.706 Alberts et al. 1992 (SWOG 8412)] | ||
|1985-1989 | |1985-1989 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) |
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 184: | Line 135: | ||
|[https://doi.org/10.1200/JCO.1992.10.5.718 Swenerton et al. 1992] | |[https://doi.org/10.1200/JCO.1992.10.5.718 Swenerton et al. 1992] | ||
|1985-1989 | |1985-1989 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) |
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] | + | *[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | + | '''28-day cycle for 6 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SWOG 8412:''' Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. [https://doi.org/10.1200/JCO.1992.10.5.706 link to original article] '''contains | + | # '''SWOG 8412:''' Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. [https://doi.org/10.1200/JCO.1992.10.5.706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1569443/ PubMed] |
− | # Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. [https://doi.org/10.1200/JCO.1992.10.5.718 link to original article] '''contains | + | # Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. [https://doi.org/10.1200/JCO.1992.10.5.718 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1569444/ PubMed] |
==CEP {{#subobject:e7b241|Regimen=1}}== | ==CEP {{#subobject:e7b241|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CEP: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>P</u>'''latinol (Cisplatin) | CEP: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>P</u>'''latinol (Cisplatin) | ||
− | ===Regimen {{#subobject:c7912c|Variant=1}}=== | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #1 {{#subobject:c7912c|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 213: | Line 163: | ||
|[https://doi.org/10.1097/00001813-199903000-00001 Wils et al. 1999] | |[https://doi.org/10.1097/00001813-199903000-00001 Wils et al. 1999] | ||
|1988-1995 | |1988-1995 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |EP | + | |[[#Cisplatin_.26_Epirubicin_999|EP]] |
| style="background-color:#ffffbf" |Did not meet endpoints of pCR rate/OS | | style="background-color:#ffffbf" |Did not meet endpoints of pCR rate/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==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2 {{#subobject:c7jcnc|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.ncbi.nlm.nih.gov/pmc/articles/PMC2360456/ Ray-Coquard et al. 2007] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360456/ Ray-Coquard et al. 2007] | ||
|1994-1997 | |1994-1997 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#CEP|CEP]]; intensified | |[[#CEP|CEP]]; intensified | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | ||
|- | |- | ||
|} | |} | ||
− | ''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==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Epirubicin (Ellence)]] | + | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Wils J, van Geuns H, Stoot J, Bergmans M, Boschma F, Bron H, Degen J, Erdkamp F, van Erp J, Haest J, Iding R, Lalisang F, de Pree N, de Rooy C, Snijders M, Schepers J, Vreeswijk J, Wals J, Werter M, Wetzels L, Smeets J, Schouten L. Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg. Anticancer Drugs. 1999 Mar;10(3):257-61. [https://doi.org/10.1097/00001813-199903000-00001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10327029 PubMed] | + | # Wils J, van Geuns H, Stoot J, Bergmans M, Boschma F, Bron H, Degen J, Erdkamp F, van Erp J, Haest J, Iding R, Lalisang F, de Pree N, de Rooy C, Snijders M, Schepers J, Vreeswijk J, Wals J, Werter M, Wetzels L, Smeets J, Schouten L. Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg. Anticancer Drugs. 1999 Mar;10(3):257-61. [https://doi.org/10.1097/00001813-199903000-00001 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10327029/ PubMed] |
− | # Ray-Coquard I, Paraiso D, Guastalla JP, Leduc B, Guichard F, Martin C, Chauvenet L, Haddad-Guichard Z, Lepillé D, Orfeuvre H, Gautier H, Castera D, Pujade-Lauraine E; GINECO. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group. Br J Cancer. 2007 Nov 5;97(9):1200-5. Epub 2007 Oct 9. [https:// | + | # Ray-Coquard I, Paraiso D, Guastalla JP, Leduc B, Guichard F, Martin C, Chauvenet L, Haddad-Guichard Z, Lepillé D, Orfeuvre H, Gautier H, Castera D, Pujade-Lauraine E; GINECO. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group. Br J Cancer. 2007 Nov 5;97(9):1200-5. Epub 2007 Oct 9. [https://doi.org/10.1038/sj.bjc.6604026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360456/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17923867/ PubMed] |
==CHAD {{#subobject:425a65|Regimen=1}}== | ==CHAD {{#subobject:425a65|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CHAD: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''exalen (Altretamine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''DP (Cisplatin) | CHAD: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''exalen (Altretamine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''DP (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:0f408a|Variant=1}}=== | ===Regimen {{#subobject:0f408a|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/10.1002/(SICI)1097-0142(19960215)77:4%3C733::AID-CNCR20%3E3.0.CO;2-0 Wadler et al. 1996 (ECOG E2878)] |
|1978-1980 | |1978-1980 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Melphalan_monotherapy|Melphalan]] | |[[#Melphalan_monotherapy|Melphalan]] | ||
| style="background-color:#91cf60" |Seems to have superior TTTF | | style="background-color:#91cf60" |Seems to have superior TTTF | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Altretamine (Hexalen)]] | + | *[[Altretamine (Hexalen)]] 150 mg/m<sup>2</sup> PO once per day on days 8 to 21 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 |
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''ECOG E2878:''' Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. [https:// | + | # '''ECOG E2878:''' Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. [https://doi.org/10.1002/(SICI)1097-0142(19960215)77:4%3C733::AID-CNCR20%3E3.0.CO;2-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8616766/ PubMed] |
==Chlorambucil & Cisplatin {{#subobject:aa1237|Regimen=1}}== | ==Chlorambucil & Cisplatin {{#subobject:aa1237|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:33fbb6|Variant=1}}=== | ===Regimen {{#subobject:33fbb6|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/S0140-6736(81)92625-8 Barker & Wiltshaw 1981] |
|1976-1979 | |1976-1979 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Chlorambucil, Cisplatin, Doxorubicin | + | |[[#Chlorambucil.2C_Cisplatin.2C_Doxorubicin_999|Chlorambucil, Cisplatin, Doxorubicin]] |
| style="background-color:#ffffbf" |Did not meet endpoint of ORR | | style="background-color:#ffffbf" |Did not meet endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Chlorambucil (Leukeran)]] | + | *[[Chlorambucil (Leukeran)]] 0.15 mg/kg PO once per day on days 2 to 8 |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycle for 12 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Barker GH, Wiltshaw E. Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Lancet. 1981 Apr 4;1(8223):747-50. [https:// | + | # Barker GH, Wiltshaw E. Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Lancet. 1981 Apr 4;1(8223):747-50. [https://doi.org/10.1016/S0140-6736(81)92625-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6110955/ PubMed] |
+ | ==CISCA {{#subobject:379e5f|Regimen=1}}== | ||
+ | CISCA: '''<u>CIS</u>'''platin, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin) | ||
+ | <br>CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <br>DCP: '''<u>D</u>'''oxorubicin, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <br>PAC: '''<u>P</u>'''latinol (Cisplatin), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:e7847b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/1097-0142(19860501)57:9%3C1725::AID-CNCR2820570903%3E3.0.CO;2-J Omura et al. 1986 (GOG 47)] | ||
+ | |1979-1982 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]] | ||
+ | | style="background-color:#1a9850" |Superior CR rate | ||
+ | | | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1016/0090-8258(89)90841-x Alberts et al. 1989 (SWOG S7925)] | ||
+ | |rowspan=2|1979-1984 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#DC_.26_BCG_999|DC & BCG]] | ||
+ | | style="background-color:#1a9850" |Superior OS | ||
+ | | | ||
+ | |- | ||
+ | |2. [[#DCP_.26_BCG_999|DCP & BCG]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(87)92381-6 Bolis et al. 1987] | ||
+ | |1980-1985 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#Cisplatin_monotherapy|Cisplatin]]<br>2. [[#Cisplatin_.26_Cyclophosphamide_2|CP]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1989.7.4.457 Omura et al. 1989 (GOG 52)] | ||
+ | |1981-1985 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Cisplatin_.26_Cyclophosphamide_2|CP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24 | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1986.4.6.965 Conte et al. 1986] | ||
+ | |1982-1984 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Cisplatin_.26_Cyclophosphamide_2|CP]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior surgical CR rate | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/0090-8258(90)90244-f Creasman et al. 1990 (GOG 60)] | ||
+ | |1982-1986 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#CAP_.26_BCG_999|CAP & BCG]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoints of PFS/OS | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(98)04119-1 Parmar et al. 1998 (ICON2)] | ||
+ | |1991-1996 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Ovarian_cancer#Carboplatin_monotherapy|Carboplatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | | style="background-color:#d73027" |More toxic | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(02)09738-6 Parmar et al. 2002 (ICON3)] | ||
+ | |1995-1998 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[Ovarian_cancer#Carboplatin_monotherapy|Carboplatin]]<br>2. [[Ovarian_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_2|Carboplatin & Paclitaxel]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | | | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 30 minutes once on day 1 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''GOG 47:''' Omura G, Blessing JA, Ehrlich CE, Miller A, Yordan E, Creasman WT, Homesley HD. A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma: a Gynecologic Oncology Group study. Cancer. 1986 May 1;57(9):1725-30. [https://doi.org/10.1002/1097-0142(19860501)57:9%3C1725::AID-CNCR2820570903%3E3.0.CO;2-J link to original article] [https://pubmed.ncbi.nlm.nih.gov/3513943/ PubMed] | ||
+ | # Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. [https://doi.org/10.1200/JCO.1986.4.6.965 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3519886/ PubMed] | ||
+ | # Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. [https://doi.org/10.1016/S0140-6736(87)92381-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2886821/ PubMed] | ||
+ | # '''SWOG S7925:''' Alberts DS, Mason-Liddil N, O'Toole RV, Abbott TM, Kronmal R, Hilgers RD, Surwit EA, Eyre HJ, Baker LH. Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: a Southwest Oncology Group Study. Gynecol Oncol. 1989 Jan;32(1):8-15. [https://doi.org/10.1016/0090-8258(89)90841-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/2642455/ PubMed] | ||
+ | # '''GOG 52:''' Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. [https://doi.org/10.1200/JCO.1989.7.4.457 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2926470/ PubMed] | ||
+ | # '''GOG 60:''' Creasman WT, Omura GA, Brady MF, Yordan E, DiSaia PJ, Beecham J. A randomized trial of cyclophosphamide, doxorubicin, and cisplatin with or without bacillus Calmette-Guerin in patients with suboptimal stage III and IV ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):239-43. [https://doi.org/10.1016/0090-8258(90)90244-f link to original article] [https://pubmed.ncbi.nlm.nih.gov/2258063/ PubMed] | ||
+ | # '''Meta-analysis:''' The Ovarian Cancer Meta-Analysis Project. Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol. 1991 Sep;9(9):1668-74. [https://doi.org/10.1200/JCO.1991.9.9.1668 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1831495/ PubMed] | ||
+ | # '''ICON2:''' Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. [https://doi.org/10.1016/S0140-6736(98)04119-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9843101/ PubMed] | ||
+ | # '''ICON3:''' Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. [https://doi.org/10.1016/s0140-6736(02)09738-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12241653/ PubMed] | ||
==Cisplatin monotherapy {{#subobject:bb1237|Regimen=1}}== | ==Cisplatin monotherapy {{#subobject:bb1237|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #1, 50 mg/m<sup>2</sup> {{#subobject:50cbb6|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(87)92381-6 Bolis et al. 1987] | ||
+ | |1980-1985 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |1. [[#CISCA|CAP]]<br>2. [[#Cisplatin_.26_Cyclophosphamide_2|CP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject:88fbb6|Variant=1}}=== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 30 minutes once on day 1 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, 75 mg/m<sup>2</sup> {{#subobject:88fbb6|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/10.1093/jnci/djq530 Fruscio et al. 2011] |
|1988-1992 | |1988-1992 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Cisplatin_monotherapy|Cisplatin]]; weekly | |[[#Cisplatin_monotherapy|Cisplatin]]; weekly | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #3, 100 mg/m<sup>2</sup> {{#subobject:88fbb6|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/10.1093/jnci/81.19.1464 Mangioni et al. 1989] | ||
+ | |1985-01 to 1987-02 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Carboplatin_monotherapy|Carboplatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 minutes once on day 1 | ||
+ | '''1-month cycle for 5 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #4, 100 mg/m<sup>2</sup> with step-down {{#subobject:88hhvc|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.1994.12.10.2066 Taylor et al. 1994] | ||
+ | |1981-10 to 1984-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Ovarian_cancer#Carboplatin_monotherapy_2|Carboplatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 5: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **Cycles 6 to 10: 30 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''28-day cycle for 10 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. [https:// | + | # Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. [https://doi.org/10.1016/S0140-6736(87)92381-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2886821/ PubMed] |
− | # Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. [https://doi.org/10.1200/JCO.1994.12.10.2066 link to original article] '''contains | + | # Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. [https://doi.org/10.1093/jnci/81.19.1464 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2674459/ PubMed] |
− | # Fruscio R, Garbi A, Parma G, Lissoni AA, Garavaglia D, Bonazzi CM, Dell'anna T, Mangioni C, Milani R, Colombo N. Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer. J Natl Cancer Inst. 2011 Feb 16;103(4):347-51. Epub 2011 Jan 7. [https:// | + | # Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. [https://doi.org/10.1200/JCO.1994.12.10.2066 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7931475/ PubMed] |
+ | # Fruscio R, Garbi A, Parma G, Lissoni AA, Garavaglia D, Bonazzi CM, Dell'anna T, Mangioni C, Milani R, Colombo N. Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer. J Natl Cancer Inst. 2011 Feb 16;103(4):347-51. Epub 2011 Jan 7. [https://doi.org/10.1093/jnci/djq530 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21217084/ PubMed] | ||
==Cisplatin & Cyclophosphamide {{#subobject:d427c4|Regimen=1}}== | ==Cisplatin & Cyclophosphamide {{#subobject:d427c4|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CP: '''<u>C</u>'''yclophosphamide & '''<u>P</u>'''latinol (Cisplatin) | CP: '''<u>C</u>'''yclophosphamide & '''<u>P</u>'''latinol (Cisplatin) | ||
<br>CPC: '''<u>C</u>'''is'''<u>P</u>'''latin & '''<u>C</u>'''yclophosphamide | <br>CPC: '''<u>C</u>'''is'''<u>P</u>'''latin & '''<u>C</u>'''yclophosphamide | ||
<br>PC: '''<u>P</u>'''latinol (Cisplatin) & '''<u>C</u>'''yclophosphamide | <br>PC: '''<u>P</u>'''latinol (Cisplatin) & '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen variant #1, 50/600 {{#subobject:dce04e|Variant=1}}=== | ===Regimen variant #1, 50/600 {{#subobject:dce04e|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 335: | Line 460: | ||
|[https://doi.org/10.1200/JCO.1986.4.6.965 Conte et al. 1986] | |[https://doi.org/10.1200/JCO.1986.4.6.965 Conte et al. 1986] | ||
|1982-1984 | |1982-1984 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#CISCA|PAC]] |
| style="background-color:#fc8d59" |Seems to have inferior surgical CR rate | | style="background-color:#fc8d59" |Seems to have inferior surgical CR rate | ||
|- | |- | ||
|} | |} | ||
+ | <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 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''28-day cycle for 6 cycles''' | '''28-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant #2, 50/750 {{#subobject:8bd325|Variant=1}}=== | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #2, 50/650 {{#subobject:ct3c4e|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(87)92381-6 Bolis et al. 1987] | ||
+ | |1980-1985 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |1. [[#Cisplatin_monotherapy|Cisplatin]]<br>2. [[#CISCA|CAP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #3, 50/750 {{#subobject:8bd325|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/10.1016/0140-6736(92)91404-V Kaye et al. 1992] |
|1988-1991 | |1988-1991 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-de-esc) |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]; 100/750 | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]; 100/750 | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*GOG 111: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with suboptimal debulking | *GOG 111: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with suboptimal debulking | ||
+ | </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 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #4, 50/1000 {{#subobject:478e8d|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 385: | Line 530: | ||
|[https://doi.org/10.1200/JCO.1989.7.4.457 Omura et al. 1989 (GOG 52)] | |[https://doi.org/10.1200/JCO.1989.7.4.457 Omura et al. 1989 (GOG 52)] | ||
|1981-1985 | |1981-1985 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#CISCA|CAP]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24 | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24 | ||
|- | |- | ||
|} | |} | ||
+ | <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 | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 8 cycles''' | '''21-day cycle for 8 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #5, 75/600 {{#subobject:671b07|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 406: | Line 552: | ||
|[https://doi.org/10.1200/JCO.1992.10.5.718 Swenerton et al. 1992] | |[https://doi.org/10.1200/JCO.1992.10.5.718 Swenerton et al. 1992] | ||
|1985-1989 | |1985-1989 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Carboplatin_.26_Cyclophosphamide|Carboplatin & Cyclophosphamide]] | |[[#Carboplatin_.26_Cyclophosphamide|Carboplatin & Cyclophosphamide]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''28-day cycle for 6 cycles''' | '''28-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #6, 75/700 {{#subobject:a5cb07|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://ar.iiarjournals.org/content/27/1B/681.long Mouratidou et al. 2007] | ||
+ | |1998-2002 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #7, 75/750 {{#subobject:1f4833|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/NEJM199503093321002 van der Burg et al. 1995] |
|1987-1993 | |1987-1993 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]], with interval debulking | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]], with interval debulking | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
Line 433: | Line 602: | ||
|[https://pubmed.ncbi.nlm.nih.gov/12530019 Breitbach et al. 2002] | |[https://pubmed.ncbi.nlm.nih.gov/12530019 Breitbach et al. 2002] | ||
|1988-NR | |1988-NR | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Cisplatin & Treosulfan | + | |[[#Cisplatin_.26_Treosulfan_999|Cisplatin & Treosulfan]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP | | style="background-color:#ffffbf" |Did not meet primary endpoint of TTP | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199601043340101 McGuire et al. 1996 (GOG 111)] |
|NR | |NR | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] | |[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/92.9.699 Piccart et al. 2000 (OV10)] |
− | |1994-1995 | + | |1994-04 to 1995-08 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] | |[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
Line 451: | Line 620: | ||
|} | |} | ||
''Note: the dosing for Breitbach et al. 2002 could not be confirmed from the abstract.'' | ''Note: the dosing for Breitbach et al. 2002 could not be confirmed from the abstract.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*GOG 111: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with suboptimal debulking | *GOG 111: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with suboptimal debulking | ||
*OV10: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with optimal or suboptimal debulking | *OV10: [[Surgery#Primary_debulking_surgery|Primary debulking surgery]], with optimal or suboptimal debulking | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
− | ===Regimen variant # | + | ===Regimen variant #8, 100/600 {{#subobject:ec6d77|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 470: | Line 643: | ||
|[https://doi.org/10.1200/JCO.1992.10.5.706 Alberts et al. 1992 (SWOG 8412)] | |[https://doi.org/10.1200/JCO.1992.10.5.706 Alberts et al. 1992 (SWOG 8412)] | ||
|1985-1989 | |1985-1989 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Carboplatin_.26_Cyclophosphamide|Carboplatin & Cyclophosphamide]] | |[[#Carboplatin_.26_Cyclophosphamide|Carboplatin & Cyclophosphamide]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199612263352603 Alberts et al. 1996 (GOG 104)] |
+ | |1986-1992 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#IP_Cisplatin_.26_Cyclophosphamide|Cisplatin (IP) & Cyclophosphamide]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0959-8049(03)00152-7 Dittrich et al. 2003] | ||
|1990-1993 | |1990-1993 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Carboplatin & Cisplatin | + | |[[#Carboplatin_.26_Cisplatin_999|Carboplatin & Cisplatin]] |
− | | 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 |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ Windbichler et al. 2000] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ Windbichler et al. 2000] | ||
|1991-1997 | |1991-1997 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Cisplatin.2C_Cyclophosphamide.2C_Interferon_gamma-1b|Cisplatin, Cyclophosphamide, IFN gamma]] | |[[#Cisplatin.2C_Cyclophosphamide.2C_Interferon_gamma-1b|Cisplatin, Cyclophosphamide, IFN gamma]] | ||
| 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)]] 100 mg/m<sup>2</sup> IV once on either day 1 or 2 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on either day 1 or 2 | ||
− | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 60 to 90 minutes once on day 1 |
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #9, 100/750 {{#subobject:1f5117|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/10.1016/0140-6736(92)91404-V Kaye et al. 1992] |
|1988-1991 | |1988-1991 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]; 50/750 | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]]; 50/750 | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #10, 100/1000 {{#subobject:11cbae|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 530: | Line 705: | ||
|[https://doi.org/10.1023/a:1012556627852 Misset et al. 2001] | |[https://doi.org/10.1023/a:1012556627852 Misset et al. 2001] | ||
|NR | |NR | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 2/3 (C) |
− | |Cyclophosphamide & Oxaliplatin | + | |[[#Cyclophosphamide_.26_Oxaliplatin_999|Cyclophosphamide & Oxaliplatin]] |
| style="background-color:#ffffbf" |Did not meet endpoints of PFS/OS | | style="background-color:#ffffbf" |Did not meet endpoints of PFS/OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. [https://doi.org/10.1200/JCO.1986.4.6.965 link to original article] '''contains | + | # Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. [https://doi.org/10.1200/JCO.1986.4.6.965 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3519886/ PubMed] |
− | # Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. [https:// | + | # Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. [https://doi.org/10.1016/S0140-6736(87)92381-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2886821/ PubMed] |
− | # '''GOG 52:''' Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. [https://doi.org/10.1200/JCO.1989.7.4.457 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2926470 PubMed] | + | # '''GOG 52:''' Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. [https://doi.org/10.1200/JCO.1989.7.4.457 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2926470/ PubMed] |
− | # '''SWOG 8412:''' Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. [https://doi.org/10.1200/JCO.1992.10.5.706 link to original article] '''contains | + | # '''SWOG 8412:''' Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. [https://doi.org/10.1200/JCO.1992.10.5.706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1569443/ PubMed] |
− | # Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. [https://doi.org/10.1200/JCO.1992.10.5.718 link to original article] '''contains | + | # Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. [https://doi.org/10.1200/JCO.1992.10.5.718 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1569444/ PubMed] |
− | # Kaye SB, Lewis CR, Paul J, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Atkinson RJ, Soukop M, Rankin EM, Cassidy J, Davis JA, Reed NS, Crawford SM, MacLean A, Swapp GA, Sarkar TK, Kennedy JH, Symonds RP. Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. Lancet. 1992 Aug 8;340(8815):329-33. [https:// | + | # Kaye SB, Lewis CR, Paul J, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Atkinson RJ, Soukop M, Rankin EM, Cassidy J, Davis JA, Reed NS, Crawford SM, MacLean A, Swapp GA, Sarkar TK, Kennedy JH, Symonds RP. Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. Lancet. 1992 Aug 8;340(8815):329-33. [https://doi.org/10.1016/0140-6736(92)91404-V link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1353804/ PubMed] |
− | # van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S; Gynecological Cancer Cooperative Group of the European Organisation for Research and Treatment of Cancer. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med. 1995 Mar 9;332(10):629-34. [https:// | + | # van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S; Gynecological Cancer Cooperative Group of the European Organisation for Research and Treatment of Cancer. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med. 1995 Mar 9;332(10):629-34. [https://doi.org/10.1056/NEJM199503093321002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7845426/ PubMed] |
− | # '''GOG 111:''' McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. [https:// | + | # '''GOG 111:''' McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. [https://doi.org/10.1056/NEJM199601043340101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7494563/ PubMed] |
− | # | + | # '''GOG 104:''' Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. [https://doi.org/10.1056/NEJM199612263352603 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8960474/ PubMed] |
− | # | + | # Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. [https://doi.org/10.1054/bjoc.1999.1053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10735496/ PubMed] |
− | # | + | # '''OV10:''' Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. [https://doi.org/10.1093/jnci/92.9.699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10793106/ PubMed] |
− | # | + | # Misset JL, Vennin P, Chollet PH, Pouillart P, Laplaige PH, Frobert JL, Castera D, Fabbro M, Langlois D, Cortesi E, Lucas V, Gamelin E, Laadem A, Otero J. Multicenter phase II-III study of oxaliplatin plus cyclophosphamide vs cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients. Ann Oncol. 2001 Oct;12(10):1411-5. [https://doi.org/10.1023/a:1012556627852 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11762813/ PubMed] |
− | # | + | # Breitbach GP, Meden H, Schmid H, Kühn W, Sass G, Schach S, Schmidt-Rohde P, Bastert G; GTOC Study Group. Treosulfan in the treatment of advanced ovarian cancer: a randomised co-operative multicentre phase III-study. Anticancer Res. 2002 Sep-Oct;22(5):2923-32. [https://pubmed.ncbi.nlm.nih.gov/12530019/ PubMed] |
− | + | # Dittrich Ch, Sevelda P, Salzer H, Obermair A, Speiser P, Breitenecker G, Schemper M, Kaider A; Austrian Ovarian Cancer Study Group. Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients: 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin. Eur J Cancer. 2003 May;39(8):1129-40. Erratum in: Eur J Cancer. 2004 Mar;40(4):627. [https://doi.org/10.1016/s0959-8049(03)00152-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12736113/ PubMed] | |
+ | # Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. [https://ar.iiarjournals.org/content/27/1B/681.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17348460/ PubMed] | ||
==Cisplatin, Cyclophosphamide, Interferon gamma-1b {{#subobject:d616c4|Regimen=1}}== | ==Cisplatin, Cyclophosphamide, Interferon gamma-1b {{#subobject:d616c4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:ec6d99|Variant=1}}=== | ===Regimen {{#subobject:ec6d99|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 572: | Line 745: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ Windbichler et al. 2000] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ Windbichler et al. 2000] | ||
|1991-1997 | |1991-1997 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | |[[#Cisplatin_.26_Cyclophosphamide_2|Cisplatin & Cyclophosphamide]] | ||
| style="background-color:#91cf60" |Seems to have superior PFS | | style="background-color:#91cf60" |Seems to have superior PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Interferon gamma-1b (Actimmune)]] | + | *[[Interferon gamma-1b (Actimmune)]] 0.1 mg SC once per day on days 1, 3, 5, 15, 17, 19 |
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. [https:// | + | # Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. [https://doi.org/10.1054/bjoc.1999.1053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363351/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10735496/ PubMed] |
==Hexa-CAF {{#subobject:d05939|Regimen=1}}== | ==Hexa-CAF {{#subobject:d05939|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Hexa-CAF: '''<u>H</u>'''exalen (Altretamine), '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''drucil (Fluorouracil), '''<u>F</u>'''olex (Methotrexate) | Hexa-CAF: '''<u>H</u>'''exalen (Altretamine), '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''drucil (Fluorouracil), '''<u>F</u>'''olex (Methotrexate) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:69d2c|Variant=1}}=== | ===Regimen {{#subobject:69d2c|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/NEJM197812072992301 Young et al. 1978] |
|1972-1977 | |1972-1977 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Melphalan_monotherapy|Melphalan]] | |[[#Melphalan_monotherapy|Melphalan]] | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(84)90594-4 Neijt et al. 1984] |
|1979-1981 | |1979-1981 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |CHAP-5 | + | |[[#CHAP-5_888|CHAP-5]] |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Altretamine (Hexalen)]] | + | *[[Altretamine (Hexalen)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 14 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14 |
− | *[[Fluorouracil (5-FU)]] | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. [https:// | + | # Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. [https://doi.org/10.1056/NEJM197812072992301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/101843/ PubMed] |
− | # Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Vriesendorp R, Kooyman CD, van Lindert AC, Hamerlynck JV, van Lent M, van Houwelingen JC, Pinedo HM. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984 Sep 15;2(8403):594-600. [https:// | + | # Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Vriesendorp R, Kooyman CD, van Lindert AC, Hamerlynck JV, van Lent M, van Houwelingen JC, Pinedo HM. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984 Sep 15;2(8403):594-600. [https://doi.org/10.1016/S0140-6736(84)90594-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6147640/ PubMed] |
==Melphalan monotherapy {{#subobject:d05939|Regimen=1}}== | ==Melphalan monotherapy {{#subobject:d05939|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:69d2c|Variant=1}}=== | ===Regimen {{#subobject:69d2c|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/10.1002/1097-0142(19800515)45:10%3C2529::AID-CNCR2820451011%3E3.0.CO;2-4 Park et al. 1980 (GOG 3)] |
|1971-1976 | |1971-1976 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |1. 5-FU & Melphalan<br> 2. 5-FU, Dactinomycin, Melphalan<br> 3. 5-FU, Cyclophosphamide, Dactinomycin | + | |1. [[#Fluorouracil_.26_Melphalan_999|5-FU & Melphalan]]<br>2. [[#Cyclophosphamide.2C_Dactinomycin.2C_Fluorouracil_999|5-FU, Dactinomycin, Melphalan<br> 3. 5-FU, Cyclophosphamide, Dactinomycin]] |
− | | style="background-color:#ffffbf" |Did not meet | + | | style="background-color:#ffffbf" |Did not meet endpoints of PFS/OS |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM197812072992301 Young et al. 1978] |
|1972-1977 | |1972-1977 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Hexa-CAF|Hexa-CAF]] | |[[#Hexa-CAF|Hexa-CAF]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
Line 647: | Line 820: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704783/ Miller et al. 1980] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704783/ Miller et al. 1980] | ||
|1974-1977 | |1974-1977 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |5-FU, Melphalan, MTX | + | |[[#Fluorouracil.2C_Melphalan.2C_Methotrexate_999|5-FU, Melphalan, MTX]] |
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS | | style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/1097-0142(19830301)51:5%3C783::AID-CNCR2820510506%3E3.0.CO;2-Z Omura et al. 1983 (GOG 22)] |
|1976-1979 | |1976-1979 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |1. Altretamine & Melphalan<br> 2. AC | + | |1. [[#Altretamine_.26_Melphalan_888|Altretamine & Melphalan]]<br>2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_888|AC]] |
| style="background-color:#fc8d59" |Seems to have inferior CR rate | | style="background-color:#fc8d59" |Seems to have inferior CR rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/(SICI)1097-0142(19960215)77:4%3C733::AID-CNCR20%3E3.0.CO;2-0 Wadler et al. 1996 (ECOG E2878)] |
|1978-1980 | |1978-1980 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#CHAD|CHAD]] | |[[#CHAD|CHAD]] | ||
| style="background-color:#fc8d59" |Seems to have inferior TTTF | | style="background-color:#fc8d59" |Seems to have inferior TTTF | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] 3.5 mg/m<sup>2</sup> PO twice per day on days 1 to 5 |
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. [https://doi.org/10.1056/NEJM197812072992301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/101843/ PubMed] | ||
+ | # '''GOG 3:''' Park RC, Blom J, Disaia PJ, Lagasse LD, Blessing JA. Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone in combination with 5-fluorouracil and dactinomycin or with the combination of cytoxan, 5-fluorouracil and dactinomycin. Cancer. 1980 May 15;45(10):2529-42. [https://doi.org/10.1002/1097-0142(19800515)45:10%3C2529::AID-CNCR2820451011%3E3.0.CO;2-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7378989/ PubMed] | ||
+ | # Miller AB, Klaassen DJ, Boyes DA, Dodds DJ, Gerulath A, Kirk ME, Levitt M, Pearson JG, Wall C. Combination v sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer. Can Med Assoc J. 1980 Sep 6;123(5):365-71. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1704783/ link to original article] [https://pubmed.ncbi.nlm.nih.gov/7020903/ PubMed] | ||
+ | # '''GOG 22:''' Omura GA, Morrow CP, Blessing JA, Miller A, Buchsbaum HJ, Homesley HD, Leone L. A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma. Cancer. 1983 Mar 1;51(5):783-9. [https://doi.org/10.1002/1097-0142(19830301)51:5%3C783::AID-CNCR2820510506%3E3.0.CO;2-Z link to original article] [https://pubmed.ncbi.nlm.nih.gov/6401594/ PubMed] | ||
+ | # '''ECOG E2878:''' Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. [https://doi.org/10.1002/(SICI)1097-0142(19960215)77:4%3C733::AID-CNCR20%3E3.0.CO;2-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8616766/ PubMed] | ||
+ | =Maintenance after first-line therapy= | ||
+ | ==Altretamine monotherapy {{#subobject:fb91d1|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:284dfe|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.2001.6274 Rothenberg et al. 2001 (SWOG-9326)] | ||
+ | |1993-1997 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Altretamine (Hexalen)]] 260 mg/m<sup>2</sup>/day PO on days 1 to 14, split into 4 daily doses | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''SWOG-9326:''' Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. [https://doi.org/10.1006/gyno.2001.6274 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11531286/ PubMed] |
− | # ''' | + | ## '''Update:''' Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. [https://doi.org/10.1111/j.1048-891x.2004.014204.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15086720/ PubMed] |
− | + | =Second-line therapy for relapsed or recurrent disease, platinum-sensitive= | |
− | # ''' | + | ==Rucaparib monotherapy {{#subobject:72fd0c|Regimen=1}}== |
− | # ''' | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen {{#subobject:68aa39|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/S1470-2045(16)30559-9 Swisher et al. 2016 (ARIEL2)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-190-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2013-10-30 to 2014-12-19 | ||
+ | |style="background-color:#91cf61"|Phase 2 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the MCBS score is for the BRCA-mutated subgroup, only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rucaparib (Rubraca)]] 600 mg PO twice per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''ARIEL2:''' Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. [https://doi.org/10.1016/S1470-2045(16)30559-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27908594/ PubMed] [https://clinicaltrials.gov/study/NCT01891344 NCT01891344] | ||
+ | ##'''Pooled subgroup analysis:''' Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. [https://doi.org/10.1136/ijgc-2019-000623 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31685558/ PubMed] | ||
=Second-line therapy= | =Second-line therapy= | ||
− | ==Altretamine & Cisplatin {{#subobject:16b701|Regimen=1}}== | + | ==Altretamine & Cisplatin (HD) {{#subobject:16b701|Regimen=1}}== |
− | + | HD: '''<u>H</u>'''examethylmelamine (Altretamine) & '''<u>D</u>'''DP (Cisplatin) | |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
===Regimen {{#subobject:ffbc8c|Variant=1}}=== | ===Regimen {{#subobject:ffbc8c|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/10.1001/jama.1979.03290440030023 Vogl et al. 1979] |
+ | |1976-1977 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Altretamine (Hexalen)]] | + | *[[Altretamine (Hexalen)]] 200 mg/m<sup>2</sup>/day PO on days 8 to 21, in divided doses |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Vogl SE, Greenwald E, Kaplan BH, Moukhtar M, Wollner D. Ovarian cancer: effective treatment after alkylating-agent failure. JAMA. 1979 May 4;241(18):1908-11. [https:// | + | # Vogl SE, Greenwald E, Kaplan BH, Moukhtar M, Wollner D. Ovarian cancer: effective treatment after alkylating-agent failure. JAMA. 1979 May 4;241(18):1908-11. [https://doi.org/10.1001/jama.1979.03290440030023 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/107337/ PubMed] |
− | == | + | ==CISCA {{#subobject:268e5f|Regimen=1}}== |
− | + | CISCA: '''<u>CIS</u>'''platin, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin) | |
− | + | <br>CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin) | |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin) | ||
===Regimen {{#subobject:e7762b|Variant=1}}=== | ===Regimen {{#subobject:e7762b|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 711: | Line 937: | ||
|[https://doi.org/10.1200/JCO.2002.20.5.1232 Cantù et al. 1999] | |[https://doi.org/10.1200/JCO.2002.20.5.1232 Cantù et al. 1999] | ||
|1992-1995 | |1992-1995 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[Ovarian_cancer#Paclitaxel_monotherapy_2|Paclitaxel]] | |[[Ovarian_cancer#Paclitaxel_monotherapy_2|Paclitaxel]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1 |
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. [https://doi.org/10.1200/JCO.2002.20.5.1232 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11870165 PubMed] | + | # Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. [https://doi.org/10.1200/JCO.2002.20.5.1232 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11870165/ PubMed] |
==Tamoxifen monotherapy {{#subobject:1d73e4|Regimen=1}}== | ==Tamoxifen monotherapy {{#subobject:1d73e4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:13b016|Variant=1}}=== | ===Regimen {{#subobject:13b016|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 738: | Line 964: | ||
|[https://doi.org/10.1016/j.ygyno.2010.08.002 Hurteau et al. 2010 (GOG 198)] | |[https://doi.org/10.1016/j.ygyno.2010.08.002 Hurteau et al. 2010 (GOG 198)] | ||
|2003-2007 | |2003-2007 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Thalidomide | + | |[[#Thalidomide_monotherapy_999|Thalidomide]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
− | ''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"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] 20 mg PO twice per day on days 1 to 28 |
+ | '''28-day cycle for up to 12 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''GOG 198:''' Hurteau JA, Brady MF, Darcy KM, McGuire WP, Edmonds P, Pearl ML, Ivanov I, Tewari KS, Mannel RS, Zanotti K, Benbrook DM. Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): A Gynecologic Oncology Group study. Gynecol Oncol. 2010 Dec;119(3):444-50. Epub 2010 Sep 17. [https://doi.org/10.1016/j.ygyno.2010.08.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20846715/ PubMed] [https://clinicaltrials.gov/study/NCT00041080 NCT00041080] | ||
+ | =Maintenance after second-line therapy for platinum-sensitive disease= | ||
+ | ==Niraparib monotherapy {{#subobject:eb98d9|Regimen=1}}== | ||
+ | {| class="wikitable" style="color:white; background-color:#9e4244" | ||
+ | |<small>'''AIM pathway regimen 2022-08-01'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #1, 200 mg/day {{#subobject:fajj66|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.annonc.2020.12.018 Wu et al. 2021 (NORA)] | ||
+ | |2017-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 18.3 vs 5.4 mo<br>(HR 0.32, 95% CI 0.23-0.45) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: after a mid-protocol amendment, this was the dosing for patients with bodyweight of less than 77 kg, or a platelet count of less than 150 x 10<sup>9</sup>/L.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Second-line [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]; neither specific agents, combinations, nor doses are specified in the protocol. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Niraparib (Zejula)]] 200 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, 300 mg/day {{#subobject:faee66|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/NEJMoa1611310 Mirza et al. 2016 (NOVA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-42-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2013-NR | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<sup>1</sup><br>Median PFS: 9.3 vs 3.9 mo<br>(HR 0.45, 95% CI 0.34-0.61) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.annonc.2020.12.018 Wu et al. 2021 (NORA)] | ||
+ | |2017-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 18.3 vs 5.4 mo<br>(HR 0.32, 95% CI 0.23-0.45) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is for the overall non-gBRCAm cohort.''<br> | ||
+ | ''Note: in NORA, after a mid-protocol amendment, this was the dosing for patients with bodyweight of 77 kg or more, and a platelet count of 150 x 10<sup>9</sup>/L or more.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Second-line [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]; neither specific agents, combinations, nor doses are specified in the protocol. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Niraparib (Zejula)]] 300 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NOVA:''' Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. [https://doi.org/10.1056/NEJMoa1611310 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27717299/ PubMed] [https://clinicaltrials.gov/study/NCT01847274 NCT01847274] | ||
+ | ## '''PRO analysis:''' Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vázquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. Epub 2018 Jul 17. [https://doi.org/10.1016/s1470-2045(18)30333-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30026000/ PubMed] | ||
+ | ## '''Subgroup analysis:''' Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. Epub 2019 Jun 7. [https://doi.org/10.1200/JCO.18.02238 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31173551/ PubMed] | ||
+ | ## '''Update:''' Mirza MR, Benigno B, Dørum A, Mahner S, Bessette P, Barceló IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Casado Herráez A, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. Epub 2020 Sep 25. [https://doi.org/10.1016/j.ygyno.2020.09.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32981695/ PubMed] | ||
+ | # '''NORA:''' Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, Wu LY, Liu ZL, Gao YN, Wang DB, Lou G, Yang HY, Zhou Q, Kong BH, Huang Y, Chen LP, Li GL, An RF, Wang K, Zhang Y, Yan XJ, Lu X, Lu WG, Hao M, Wang L, Cui H, Chen QH, Abulizi G, Huang XH, Tian XF, Wen H, Zhang C, Hou JM, Mirza MR. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021 Apr;32(4):512-521. Epub 2021 Jan 14. [https://doi.org/10.1016/j.annonc.2020.12.018 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33453391/ PubMed] [https://clinicaltrials.gov/study/NCT03705156 NCT03705156] | ||
+ | ==Olaparib monotherapy {{#subobject:f4c078|Regimen=1}}== | ||
+ | {| class="wikitable" style="color:white; background-color:#9e4244" | ||
+ | |<small>'''AIM pathway regimen 2022-08-01'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 600 mg/day {{#subobject:68yt3d|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.annonc.2023.09.3110 Pujade-Lauraine et al. 2023 (OReO)] | ||
+ | |2017-06-28 to 2021-02-10 | ||
+ | |style="background-color:#1a9851"|Phase 3b (E-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 5.3 vs 2.8 mo<br>(HR 0.43, 95% CI 0.26-0.71) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is for the non-BRCA-mutated cohort.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Preceding treatment==== | ||
+ | *Second-line [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Olaparib (Lynparza)]] 300 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, 800 mg/day {{#subobject:68e02d|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/NEJMoa1105535 Ledermann et al. 2012 (Study 19)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-47-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS (secondary endpoint)<sup>1</sup><br>Median OS: 29.8 vs 27.8 mo<br>(HR 0.73, 95% CI 0.55-0.95)<br><br>Superior PFS (primary endpoint)<br>Median PFS: 8.4 vs 4.8 mo<br>(HR 0.35, 95% CI 0.25-0.49) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for Study 19 is based on the 2018 update; although p=0.02, the authors state that "the predefined threshold for statistical significance was not met."'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Olaparib (Lynparza)]] 400 mg PO twice per day | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # '''Study 19:''' Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. Epub 2012 Mar 27. [https://doi.org/10.1056/NEJMoa1105535 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22452356/ PubMed] [https://clinicaltrials.gov/study/NCT00753545 NCT00753545] | ||
+ | ## '''Update:''' Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. [https://doi.org/10.1016/S1470-2045(16)30376-X link to orignal article] [https://pubmed.ncbi.nlm.nih.gov/27617661/ PubMed] | ||
+ | ## '''HRQoL analysis:''' Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. Epub 2016 Nov 8. [https://doi.org/10.1038/bjc.2016.348 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5129820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27824811/ PubMed] | ||
+ | ## '''Update:''' Friedlander M, Matulonis U, Gourley C, du Bois A, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Shirinkin V, Selle F, Fielding A, Lowe ES, McMurtry EL, Spencer S, Rowe P, Mann H, Parry D, Ledermann J. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 2018 Oct;119(9):1075-1085. Epub 2018 Oct 24. [https://doi.org/10.1038/s41416-018-0271-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6219499/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30353045/ PubMed] | ||
+ | #'''OReO:''' Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marmé F, Lindemann K, Colombo N, Mądry R, Glasspool R, Vergote I, Korach J, Lheureux S, Dubot C, Oaknin A, Zamagni C, Heitz F, Gladieff L, Rubio-Pérez MJ, Scollo P, Blakeley C, Shaw B, Ray-Coquard I, Redondo A; OReO/ENGOT-ov38 investigators. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023 Dec;34(12):1152-1164. Epub 2023 Oct 4. [https://doi.org/10.1016/j.annonc.2023.09.3110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37797734/ PubMed] [https://clinicaltrials.gov/study/NCT03106987 NCT03106987] | ||
+ | #'''ICON9:''' [https://clinicaltrials.gov/study/NCT03278717 NCT03278717] | ||
+ | |||
+ | ==Rucaparib monotherapy {{#subobject:218ca1|Regimen=1}}== | ||
+ | {| class="wikitable" style="color:white; background-color:#9e4244" | ||
+ | |<small>'''AIM pathway regimen 2022-08-01'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:5c47ff|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(17)32440-6 Coleman et al. 2017 (ARIEL3)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-191-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2014-2016 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 16.6 vs 5.4 mo<br>(HR 0.23, 95% CI 0.16-0.34) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Second-line [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rucaparib (Rubraca)]] 600 mg PO twice per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # ''' | + | # '''ARIEL3:''' Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12. [https://doi.org/10.1016/S0140-6736(17)32440-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901715/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28916367/ PubMed] [https://clinicaltrials.gov/study/NCT01968213 NCT01968213] |
+ | ## '''Update:''' Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. [https://doi.org/10.1016/s1470-2045(20)30061-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8210534/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32359490/ PubMed] | ||
+ | ## '''Update:''' Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cella D, Meunier J, Goble S, Cameron T, Maloney L, Mörk AC, Bedel J, Ledermann JA, Coleman RL. Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma. J Clin Oncol. 2020 Oct 20;38(30):3494-3505. Epub 2020 Aug 24. [https://doi.org/10.1200/jco.19.03107 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7571791/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32840418/ PubMed] | ||
+ | ##'''PRO analysis:''' Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. Epub 2023 May 30. [https://doi.org/10.1016/j.ygyno.2023.05.060 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37262961/ PubMed] | ||
− | = | + | =Relapsed or recurrent disease, platinum-resistant= |
− | == | + | ==Carboplatin monotherapy {{#subobject:f19c03|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen {{#subobject:34cc91|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/10.1093/annonc/mdt515 Fotopoulou et al. 2013 (OVATURE)] | ||
+ | |2006-2009 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Phenoxodiol_999|Carboplatin & Phenoxodiol]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 2 IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''OVATURE:''' Fotopoulou C, Vergote I, Mainwaring P, Bidzinski M, Vermorken JB, Ghamande SA, Harnett P, Del Prete SA, Green JA, Spaczynski M, Blagden S, Gore M, Ledermann J, Kaye S, Gabra H. Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study. Ann Oncol. 2014 Jan;25(1):160-5. Epub 2013 Dec 5. [https://doi.org/10.1093/annonc/mdt515 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24318743/ PubMed] [https://clinicaltrials.gov/study/NCT00382811 NCT00382811] | ||
+ | ==Niraparib monotherapy {{#subobject:eadfbd9|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:fagg66|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | {| 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/S1470-2045(19)30029-4 Moore et al. 2019 (QUADRA)] | ||
+ | |2015-2017 | ||
+ | |style="background-color:#91cf61"|Phase 2 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Niraparib (Zejula)]] 300 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''QUADRA:''' Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. [https://doi.org/10.1016/S1470-2045(19)30029-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30948273/ PubMed] [https://clinicaltrials.gov/study/NCT02354586 NCT02354586] | ||
+ | ==Olaparib monotherapy {{#subobject:6ab358|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:5cec53|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/S1470-2045%2811%2970214-5 Gelmon et al. 2011 (D0810C00020)] | ||
+ | |2008-2009 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Olaparib (Lynparza)]] 400 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''D0810C00020:''' Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. Epub 2011 Aug 19. [https://doi.org/10.1016/S1470-2045%2811%2970214-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21862407/ PubMed] | ||
+ | ==Rucaparib monotherapy {{#subobject:72fd0c|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:68aa39|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/10.1158/1078-0432.ccr-16-2796 Kristeleit et al. 2017 (Study 10)] | ||
+ | |2011-2013 | ||
+ | |style="background-color:#91cf61"|Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(22)00122-x Kristeleit et al. 2022 (ARIEL4)] | ||
+ | |2017-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |Standard-of-care chemotherapy | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.4 vs 5.7 mo<br>(HR 0.64, 95% CI 0.49-0.84) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: the OS results of ARIEL4 prompted the withdrawal of this indication for rucaparib.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *Study 10: Germline BRCA1 or BRCA2 mutation | ||
+ | *ARIEL4: BRCA1 or BRCA2 mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rucaparib (Rubraca)]] 600 mg PO twice per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # '''Study 10:''' Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4095-4106. Epub 2017 Mar 6. [https://doi.org/10.1158/1078-0432.ccr-16-2796 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/28264872/ PubMed] [https://clinicaltrials.gov/study/NCT01482715 NCT01482715] | ||
+ | ## '''Pooled subgroup analysis:''' Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. [https://doi.org/10.1136/ijgc-2019-000623 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31685558/ PubMed] | ||
+ | # '''ARIEL4:''' Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Apr;23(4):465-478. Epub 2022 Mar 14. [https://doi.org/10.1016/s1470-2045(22)00122-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35298906/ PubMed] [https://clinicaltrials.gov/study/NCT02855944 NCT02855944] | ||
+ | |||
+ | =Intraperitoneal therapy= | ||
+ | ==IP Cisplatin & Cyclophosphamide {{#subobject:06c9ec|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:680f73|Variant=1}}=== | ===Regimen {{#subobject:680f73|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/NEJM199612263352603 Alberts et al. 1996 (GOG 104)] |
|1986-1992 | |1986-1992 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Cisplatin_.26_Cyclophosphamide|Cisplatin (IV) & Cyclophosphamide]] | |[[#Cisplatin_.26_Cyclophosphamide|Cisplatin (IV) & Cyclophosphamide]] | ||
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] IP | + | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IP once on day 1 |
− | *[[Cyclophosphamide (Cytoxan)]] IV | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 60 to 90 minutes once on day 1 |
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''GOG 104:''' Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. [https:// | + | # '''GOG 104:''' Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. [https://doi.org/10.1056/NEJM199612263352603 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8960474/ PubMed] |
− | |||
[[Category:Ovarian cancer regimens]] | [[Category:Ovarian cancer regimens]] | ||
[[Category:Historical regimens]] | [[Category:Historical regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Gynecologic cancers]] | [[Category:Gynecologic cancers]] |
Latest revision as of 00:25, 30 June 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main ovarian cancer page for current regimens.
24 regimens on this page
39 variants on this page
|
Adjuvant chemotherapy for early stage disease
Cisplatin & Cyclophosphamide
CP: Cyclophosphamide & Platinol (Cisplatin)
PC: Platinol (Cisplatin) & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Young et al. 2003 (GOG 95) | 1986-1994 | Phase 3 (C) | IP P32 | Did not meet primary endpoint of OS |
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- GOG 95: Young RC, Brady MF, Nieberg RK, Long HJ, Mayer AR, Lentz SS, Hurteau J, Alberts DS. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a Gynecologic Oncology Group study. J Clin Oncol. 2003 Dec 1;21(23):4350-5. link to original article contains dosing details in abstract PubMed
Melphalan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klaassen et al. 1988 | 1975-1984 | Phase 3 (E-switch-ooc) | WAI | Seems to have superior DFS |
References
- Klaassen D, Shelley W, Starreveld A, Kirk M, Boyes D, Gerulath A, Levitt M, Fraser R, Carmichael J, Methot Y, Willan A; National Cancer Institute of Canada Clinical Trials Group. Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report. J Clin Oncol. 1988 Aug;6(8):1254-63. link to original article contains dosing details in abstract PubMed
First-line chemotherapy for advanced stage disease
Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.
Altretamine & Cisplatin (HD)
HD: Hexamethylmelamine (Altretamine) & DDP (Cisplatin)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wiernik et al. 1992a | 1979-1985 | Randomized (E-RT-de-esc) | Altretamine, Cisplatin, Pyridoxine | Not clearly reported |
Chemotherapy
- Altretamine (Hexalen) 200 mg/m2 PO once per day on days 8 to 21
- Cisplatin (Platinol) 37.5 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wiernik et al. 1992a | 1979-1985 | Randomized (E-RT-de-esc) | Altretamine, Cisplatin, Pyridoxine | Not clearly reported |
Chemotherapy
- Altretamine (Hexalen) 200 mg/m2 PO once per day on days 8 to 21
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycles
References
- Wiernik PH, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J; ECOG. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992;10(1):1-9. link to original article contains dosing details in abstract PubMed
Carboplatin & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alberts et al. 1992 (SWOG 8412) | 1985-1989 | Phase 3 (E-RT-switch-ic) | Cisplatin & Cyclophosphamide | Seems to have superior OS |
Swenerton et al. 1992 | 1985-1989 | Phase 3 (E-RT-switch-ic) | Cisplatin & Cyclophosphamide | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
References
- SWOG 8412: Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. link to original article contains dosing details in abstract PubMed
- Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. link to original article contains dosing details in manuscript PubMed
CEP
CEP: Cyclophosphamide, Epirubicin, Platinol (Cisplatin)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wils et al. 1999 | 1988-1995 | Phase 3 (C) | EP | Did not meet endpoints of pCR rate/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
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ray-Coquard et al. 2007 | 1994-1997 | Phase 3 (C) | CEP; intensified | Did not meet primary endpoint of OS24 |
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
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- Wils J, van Geuns H, Stoot J, Bergmans M, Boschma F, Bron H, Degen J, Erdkamp F, van Erp J, Haest J, Iding R, Lalisang F, de Pree N, de Rooy C, Snijders M, Schepers J, Vreeswijk J, Wals J, Werter M, Wetzels L, Smeets J, Schouten L. Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg. Anticancer Drugs. 1999 Mar;10(3):257-61. link to original article contains dosing details in abstract PubMed
- Ray-Coquard I, Paraiso D, Guastalla JP, Leduc B, Guichard F, Martin C, Chauvenet L, Haddad-Guichard Z, Lepillé D, Orfeuvre H, Gautier H, Castera D, Pujade-Lauraine E; GINECO. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group. Br J Cancer. 2007 Nov 5;97(9):1200-5. Epub 2007 Oct 9. link to original article link to PMC article contains dosing details in abstract PubMed
CHAD
CHAD: Cyclophosphamide, Hexalen (Altretamine), Adriamycin (Doxorubicin), DDP (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wadler et al. 1996 (ECOG E2878) | 1978-1980 | Phase 3 (E-esc) | Melphalan | Seems to have superior TTTF |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Altretamine (Hexalen) 150 mg/m2 PO once per day on days 8 to 21
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
28-day cycles
References
- ECOG E2878: Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. link to original article contains dosing details in manuscript PubMed
Chlorambucil & Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Barker & Wiltshaw 1981 | 1976-1979 | Phase 3 (C) | Chlorambucil, Cisplatin, Doxorubicin | Did not meet endpoint of ORR |
Chemotherapy
- Chlorambucil (Leukeran) 0.15 mg/kg PO once per day on days 2 to 8
- Cisplatin (Platinol) 20 mg/m2 IV once on day 1
21-day cycle for 12 cycles
References
- Barker GH, Wiltshaw E. Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Lancet. 1981 Apr 4;1(8223):747-50. link to original article contains dosing details in manuscript PubMed
CISCA
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
DCP: Doxorubicin, Cyclophosphamide, Platinol (Cisplatin)
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Omura et al. 1986 (GOG 47) | 1979-1982 | Phase 3 (E-esc) | AC | Superior CR rate | |
Alberts et al. 1989 (SWOG S7925) | 1979-1984 | Phase 3 (C) | 1. DC & BCG | Superior OS | |
2. DCP & BCG | Did not meet endpoint of OS | ||||
Bolis et al. 1987 | 1980-1985 | Phase 3 (C) | 1. Cisplatin 2. CP |
Seems to have superior PFS | |
Omura et al. 1989 (GOG 52) | 1981-1985 | Phase 3 (E-esc) | CP | Did not meet primary endpoint of PFS24 | |
Conte et al. 1986 | 1982-1984 | Phase 3 (E-esc) | CP | Seems to have superior surgical CR rate | |
Creasman et al. 1990 (GOG 60) | 1982-1986 | Phase 3 (C) | CAP & BCG | Did not meet endpoints of PFS/OS | |
Parmar et al. 1998 (ICON2) | 1991-1996 | Phase 3 (C) | Carboplatin | Did not meet primary endpoint of OS | More toxic |
Parmar et al. 2002 (ICON3) | 1995-1998 | Phase 3 (C) | 1. Carboplatin 2. Carboplatin & Paclitaxel |
Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 6 cycles
References
- GOG 47: Omura G, Blessing JA, Ehrlich CE, Miller A, Yordan E, Creasman WT, Homesley HD. A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma: a Gynecologic Oncology Group study. Cancer. 1986 May 1;57(9):1725-30. link to original article PubMed
- Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. link to original article PubMed
- Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article contains dosing details in manuscript PubMed
- SWOG S7925: Alberts DS, Mason-Liddil N, O'Toole RV, Abbott TM, Kronmal R, Hilgers RD, Surwit EA, Eyre HJ, Baker LH. Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: a Southwest Oncology Group Study. Gynecol Oncol. 1989 Jan;32(1):8-15. link to original article PubMed
- GOG 52: Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. link to original article PubMed
- GOG 60: Creasman WT, Omura GA, Brady MF, Yordan E, DiSaia PJ, Beecham J. A randomized trial of cyclophosphamide, doxorubicin, and cisplatin with or without bacillus Calmette-Guerin in patients with suboptimal stage III and IV ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 1990 Dec;39(3):239-43. link to original article PubMed
- Meta-analysis: The Ovarian Cancer Meta-Analysis Project. Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol. 1991 Sep;9(9):1668-74. link to original article PubMed
- ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. link to original article contains dosing details in manuscript PubMed
- ICON3: Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. link to original article PubMed
Cisplatin monotherapy
Regimen variant #1, 50 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bolis et al. 1987 | 1980-1985 | Phase 3 (E-de-esc) | 1. CAP 2. CP |
Did not meet endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 6 cycles
Regimen variant #2, 75 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fruscio et al. 2011 | 1988-1992 | Phase 3 (C) | Cisplatin; weekly | Did not meet primary endpoint of PFS |
Regimen variant #3, 100 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mangioni et al. 1989 | 1985-01 to 1987-02 | Phase 3 (C) | Carboplatin | Did not meet endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 30 minutes once on day 1
1-month cycle for 5 cycles
Regimen variant #4, 100 mg/m2 with step-down
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Taylor et al. 1994 | 1981-10 to 1984-06 | Phase 3 (C) | Carboplatin | Did not meet endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 5: 100 mg/m2 IV once on day 1
- Cycles 6 to 10: 30 mg/m2 IV once on day 1
28-day cycle for 10 cycles
References
- Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article contains dosing details in manuscript PubMed
- Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. link to original article contains dosing details in manuscript PubMed
- Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. link to original article contains dosing details in abstract PubMed
- Fruscio R, Garbi A, Parma G, Lissoni AA, Garavaglia D, Bonazzi CM, Dell'anna T, Mangioni C, Milani R, Colombo N. Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer. J Natl Cancer Inst. 2011 Feb 16;103(4):347-51. Epub 2011 Jan 7. link to original article contains dosing details in abstract PubMed
Cisplatin & Cyclophosphamide
CP: Cyclophosphamide & Platinol (Cisplatin)
CPC: CisPlatin & Cyclophosphamide
PC: Platinol (Cisplatin) & Cyclophosphamide
Regimen variant #1, 50/600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Conte et al. 1986 | 1982-1984 | Phase 3 (C) | PAC | Seems to have inferior surgical CR rate |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Regimen variant #2, 50/650
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bolis et al. 1987 | 1980-1985 | Phase 3 (E-de-esc) | 1. Cisplatin 2. CAP |
Did not meet endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Regimen variant #3, 50/750
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaye et al. 1992 | 1988-1991 | Phase 3 (E-de-esc) | Cisplatin & Cyclophosphamide; 100/750 | Inferior OS |
Preceding treatment
- GOG 111: Primary debulking surgery, with suboptimal debulking
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #4, 50/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Omura et al. 1989 (GOG 52) | 1981-1985 | Phase 3 (C) | CAP | Did not meet primary endpoint of PFS24 |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Regimen variant #5, 75/600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Swenerton et al. 1992 | 1985-1989 | Phase 3 (C) | Carboplatin & Cyclophosphamide | Did not meet primary endpoint of PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Regimen variant #6, 75/700
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mouratidou et al. 2007 | 1998-2002 | Phase 3 (C) | Cisplatin & Paclitaxel | Did not meet primary endpoint of PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #7, 75/750
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van der Burg et al. 1995 | 1987-1993 | Phase 3 (C) | Cisplatin & Cyclophosphamide, with interval debulking | Inferior OS |
Breitbach et al. 2002 | 1988-NR | Phase 3 (C) | Cisplatin & Treosulfan | Did not meet primary endpoint of TTP |
McGuire et al. 1996 (GOG 111) | NR | Phase 3 (C) | Cisplatin & Paclitaxel | Inferior OS |
Piccart et al. 2000 (OV10) | 1994-04 to 1995-08 | Phase 3 (C) | Cisplatin & Paclitaxel | Inferior OS |
Note: the dosing for Breitbach et al. 2002 could not be confirmed from the abstract.
Preceding treatment
- GOG 111: Primary debulking surgery, with suboptimal debulking
- OV10: Primary debulking surgery, with optimal or suboptimal debulking
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #8, 100/600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alberts et al. 1992 (SWOG 8412) | 1985-1989 | Phase 3 (C) | Carboplatin & Cyclophosphamide | Seems to have inferior OS |
Alberts et al. 1996 (GOG 104) | 1986-1992 | Phase 3 (C) | Cisplatin (IP) & Cyclophosphamide | Seems to have inferior OS |
Dittrich et al. 2003 | 1990-1993 | Phase 3 (C) | Carboplatin & Cisplatin | Did not meet co-primary endpoints of PFS/OS |
Windbichler et al. 2000 | 1991-1997 | Phase 3 (C) | Cisplatin, Cyclophosphamide, IFN gamma | Seems to have inferior PFS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on either day 1 or 2
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 60 to 90 minutes once on day 1
21-day cycle for 6 cycles
Regimen variant #9, 100/750
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaye et al. 1992 | 1988-1991 | Phase 3 (E-esc) | Cisplatin & Cyclophosphamide; 50/750 | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #10, 100/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Misset et al. 2001 | NR | Phase 2/3 (C) | Cyclophosphamide & Oxaliplatin | Did not meet endpoints of PFS/OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- Conte PF, Bruzzone M, Chiara S, Sertoli MR, Daga MG, Rubagotti A, Conio A, Ruvolo M, Rosso R, Santi L, Carnino F, Cottini M, Mossetti C, Guercio E, Gatti M, Siliquini PN, Prelato ML, Durando C, Giaccone G, Calciati A, Farinini D, Centonze M, Rugiati S, Parodi G, Messineo M, Storace A, Bernardini G, Misurale F, Alessandri S, Casini M, Ragni N, Foglia G, Bentivoglio G, Pescetto G. A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. J Clin Oncol. 1986 Jun;4(6):965-71. Erratum in: J Clin Oncol 1986 Aug;4(8):1284. link to original article contains dosing details in abstract PubMed
- Bolis G, Marsoni S, Belloni C, Bianchi U, Bolis PF, Bortolozzi G, Colombo N, Epis A, Giardina G, Natale N, Pecorelli S, Redaelli U, Santoienna M, Valsecchi MG, Vassena L, Vergadoro F, Mangioni C; Gruppo Interegionale Cooperativo Oncologico Ginecologia. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Lancet. 1987 Aug 15;2(8555):353-9. link to original article contains dosing details in manuscript PubMed
- GOG 52: Omura GA, Bundy BN, Berek JS, Curry S, Delgado G, Mortel R. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1989 Apr;7(4):457-65. link to original article PubMed
- SWOG 8412: Alberts DS, Green S, Hannigan EV, O'Toole R, Stock-Novack D, Anderson P, Surwit EA, Malvlya VK, Nahhas WA, Jolles CJ. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol. 1992 May;10(5):706-17. Erratum in: J Clin Oncol 1992 Sep;10(9):1505. link to original article contains dosing details in abstract PubMed
- Swenerton K, Jeffrey J, Stuart G, Roy M, Krepart G, Carmichael J, Drouin P, Stanimir R, O'Connell G, MacLean G, Kirk ME, Canetta R, Koski B, Shelley W, Zee B, Pater J; National Cancer Institute of Canada Clinical Trials Group. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1992 May;10(5):718-26. link to original article contains dosing details in manuscript PubMed
- Kaye SB, Lewis CR, Paul J, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Atkinson RJ, Soukop M, Rankin EM, Cassidy J, Davis JA, Reed NS, Crawford SM, MacLean A, Swapp GA, Sarkar TK, Kennedy JH, Symonds RP. Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. Lancet. 1992 Aug 8;340(8815):329-33. link to original article contains dosing details in abstract PubMed
- van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S; Gynecological Cancer Cooperative Group of the European Organisation for Research and Treatment of Cancer. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med. 1995 Mar 9;332(10):629-34. link to original article PubMed
- GOG 111: McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. link to original article contains dosing details in manuscript PubMed
- GOG 104: Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. link to original article contains dosing details in manuscript PubMed
- Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. link to original article link to PMC article contains dosing details in abstract PubMed
- OV10: Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. link to original article contains dosing details in manuscript PubMed
- Misset JL, Vennin P, Chollet PH, Pouillart P, Laplaige PH, Frobert JL, Castera D, Fabbro M, Langlois D, Cortesi E, Lucas V, Gamelin E, Laadem A, Otero J. Multicenter phase II-III study of oxaliplatin plus cyclophosphamide vs cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients. Ann Oncol. 2001 Oct;12(10):1411-5. link to original article contains dosing details in abstract PubMed
- Breitbach GP, Meden H, Schmid H, Kühn W, Sass G, Schach S, Schmidt-Rohde P, Bastert G; GTOC Study Group. Treosulfan in the treatment of advanced ovarian cancer: a randomised co-operative multicentre phase III-study. Anticancer Res. 2002 Sep-Oct;22(5):2923-32. PubMed
- Dittrich Ch, Sevelda P, Salzer H, Obermair A, Speiser P, Breitenecker G, Schemper M, Kaider A; Austrian Ovarian Cancer Study Group. Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients: 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin. Eur J Cancer. 2003 May;39(8):1129-40. Erratum in: Eur J Cancer. 2004 Mar;40(4):627. link to original article contains dosing details in abstract PubMed
- Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. link to original article contains dosing details in abstract PubMed
Cisplatin, Cyclophosphamide, Interferon gamma-1b
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Windbichler et al. 2000 | 1991-1997 | Phase 3 (E-esc) | Cisplatin & Cyclophosphamide | Seems to have superior PFS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Immunotherapy
- Interferon gamma-1b (Actimmune) 0.1 mg SC once per day on days 1, 3, 5, 15, 17, 19
28-day cycles
References
- Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Müller-Holzner E, Marth C. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer. 2000 Mar;82(6):1138-44. link to original article link to PMC article contains dosing details in abstract PubMed
Hexa-CAF
Hexa-CAF: Hexalen (Altretamine), Cyclophosphamide, Adrucil (Fluorouracil), Folex (Methotrexate)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Young et al. 1978 | 1972-1977 | Phase 3 (E-esc) | Melphalan | Superior OS |
Neijt et al. 1984 | 1979-1981 | Phase 3 (C) | CHAP-5 | Inferior OS |
Chemotherapy
- Altretamine (Hexalen) 150 mg/m2 PO once per day on days 1 to 14
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
28-day cycles
References
- Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. link to original article PubMed
- Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Vriesendorp R, Kooyman CD, van Lindert AC, Hamerlynck JV, van Lent M, van Houwelingen JC, Pinedo HM. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984 Sep 15;2(8403):594-600. link to original article contains dosing details in manuscript PubMed
Melphalan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 1980 (GOG 3) | 1971-1976 | Phase 3 (C) | 1. 5-FU & Melphalan 2. 5-FU, Dactinomycin, Melphalan 3. 5-FU, Cyclophosphamide, Dactinomycin |
Did not meet endpoints of PFS/OS |
Young et al. 1978 | 1972-1977 | Phase 3 (C) | Hexa-CAF | Inferior OS |
Miller et al. 1980 | 1974-1977 | Phase 3 (C) | 5-FU, Melphalan, MTX | Did not meet endpoints of ORR/OS |
Omura et al. 1983 (GOG 22) | 1976-1979 | Phase 3 (C) | 1. Altretamine & Melphalan 2. AC |
Seems to have inferior CR rate |
Wadler et al. 1996 (ECOG E2878) | 1978-1980 | Phase 3 (C) | CHAD | Seems to have inferior TTTF |
References
- Young RC, Chabner BA, Hubbard SP, Fisher RI, Bender RA, Anderson T, Simon RM, Canellos GP, DeVita VT Jr. Advanced ovarian adenocarcinoma: prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978 Dec 7;299(23):1261-6. link to original article PubMed
- GOG 3: Park RC, Blom J, Disaia PJ, Lagasse LD, Blessing JA. Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone in combination with 5-fluorouracil and dactinomycin or with the combination of cytoxan, 5-fluorouracil and dactinomycin. Cancer. 1980 May 15;45(10):2529-42. link to original article PubMed
- Miller AB, Klaassen DJ, Boyes DA, Dodds DJ, Gerulath A, Kirk ME, Levitt M, Pearson JG, Wall C. Combination v sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer. Can Med Assoc J. 1980 Sep 6;123(5):365-71. link to original article PubMed
- GOG 22: Omura GA, Morrow CP, Blessing JA, Miller A, Buchsbaum HJ, Homesley HD, Leone L. A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma. Cancer. 1983 Mar 1;51(5):783-9. link to original article PubMed
- ECOG E2878: Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878. Cancer. 1996 Feb 15;77(4):733-42. link to original article contains dosing details in manuscript PubMed
Maintenance after first-line therapy
Altretamine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rothenberg et al. 2001 (SWOG-9326) | 1993-1997 | Phase 2 |
Chemotherapy
- Altretamine (Hexalen) 260 mg/m2/day PO on days 1 to 14, split into 4 daily doses
28-day cycle for 6 cycles
References
- SWOG-9326: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. link to original article contains dosing details in abstract PubMed
- Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article PubMed
Second-line therapy for relapsed or recurrent disease, platinum-sensitive
Rucaparib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Swisher et al. 2016 (ARIEL2) | 2013-10-30 to 2014-12-19 | Phase 2 (RT) |
Note: the MCBS score is for the BRCA-mutated subgroup, only.
References
- ARIEL2: Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article contains dosing details in manuscript PubMed NCT01891344
- Pooled subgroup analysis: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. link to original article PubMed
Second-line therapy
Altretamine & Cisplatin (HD)
HD: Hexamethylmelamine (Altretamine) & DDP (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Vogl et al. 1979 | 1976-1977 | Non-randomized |
Chemotherapy
- Altretamine (Hexalen) 200 mg/m2/day PO on days 8 to 21, in divided doses
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
21-day cycles
References
- Vogl SE, Greenwald E, Kaplan BH, Moukhtar M, Wollner D. Ovarian cancer: effective treatment after alkylating-agent failure. JAMA. 1979 May 4;241(18):1908-11. link to original article contains dosing details in manuscript PubMed
CISCA
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cantù et al. 1999 | 1992-1995 | Phase 3 (C) | Paclitaxel | Seems to have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
21-day cycle for at least 6 cycles
References
- Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. link to original article contains dosing details in manuscript PubMed
Tamoxifen monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hurteau et al. 2010 (GOG 198) | 2003-2007 | Phase 3 (C) | Thalidomide | Did not meet primary endpoint of PFS |
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.
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO twice per day on days 1 to 28
28-day cycle for up to 12 cycles
References
- GOG 198: Hurteau JA, Brady MF, Darcy KM, McGuire WP, Edmonds P, Pearl ML, Ivanov I, Tewari KS, Mannel RS, Zanotti K, Benbrook DM. Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): A Gynecologic Oncology Group study. Gynecol Oncol. 2010 Dec;119(3):444-50. Epub 2010 Sep 17. link to original article contains dosing details in manuscript PubMed NCT00041080
Maintenance after second-line therapy for platinum-sensitive disease
Niraparib monotherapy
AIM pathway regimen 2022-08-01 |
Regimen variant #1, 200 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2021 (NORA) | 2017-2019 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 18.3 vs 5.4 mo (HR 0.32, 95% CI 0.23-0.45) |
Note: after a mid-protocol amendment, this was the dosing for patients with bodyweight of less than 77 kg, or a platelet count of less than 150 x 109/L.
Preceding treatment
- Second-line platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
Regimen variant #2, 300 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mirza et al. 2016 (NOVA) | 2013-NR | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint)1 Median PFS: 9.3 vs 3.9 mo (HR 0.45, 95% CI 0.34-0.61) |
Wu et al. 2021 (NORA) | 2017-2019 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 18.3 vs 5.4 mo (HR 0.32, 95% CI 0.23-0.45) |
1Reported efficacy is for the overall non-gBRCAm cohort.
Note: in NORA, after a mid-protocol amendment, this was the dosing for patients with bodyweight of 77 kg or more, and a platelet count of 150 x 109/L or more.
Preceding treatment
- Second-line platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
References
- NOVA: Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. link to original article contains dosing details in manuscript PubMed NCT01847274
- PRO analysis: Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vázquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. Epub 2018 Jul 17. link to original article PubMed
- Subgroup analysis: Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. Epub 2019 Jun 7. link to original article link to PMC article PubMed
- Update: Mirza MR, Benigno B, Dørum A, Mahner S, Bessette P, Barceló IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Casado Herráez A, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. Epub 2020 Sep 25. link to original article PubMed
- NORA: Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, Wu LY, Liu ZL, Gao YN, Wang DB, Lou G, Yang HY, Zhou Q, Kong BH, Huang Y, Chen LP, Li GL, An RF, Wang K, Zhang Y, Yan XJ, Lu X, Lu WG, Hao M, Wang L, Cui H, Chen QH, Abulizi G, Huang XH, Tian XF, Wen H, Zhang C, Hou JM, Mirza MR. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021 Apr;32(4):512-521. Epub 2021 Jan 14. link to original article contains dosing details in abstract PubMed NCT03705156
Olaparib monotherapy
AIM pathway regimen 2022-08-01 |
Regimen variant #1, 600 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2023 (OReO) | 2017-06-28 to 2021-02-10 | Phase 3b (E-esc) | Placebo | Superior PFS1 (primary endpoint) Median PFS: 5.3 vs 2.8 mo (HR 0.43, 95% CI 0.26-0.71) |
1Reported efficacy is for the non-BRCA-mutated cohort.
Preceding treatment
- Second-line platinum-based chemotherapy
Regimen variant #2, 800 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ledermann et al. 2012 (Study 19) | 2008-2010 | Randomized Phase 2 (E-RT-esc) | Placebo | Might have superior OS (secondary endpoint)1 Median OS: 29.8 vs 27.8 mo (HR 0.73, 95% CI 0.55-0.95) Superior PFS (primary endpoint) Median PFS: 8.4 vs 4.8 mo (HR 0.35, 95% CI 0.25-0.49) |
1Reported efficacy for Study 19 is based on the 2018 update; although p=0.02, the authors state that "the predefined threshold for statistical significance was not met."
References
- Study 19: Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. Epub 2012 Mar 27. link to original article contains dosing details in manuscript PubMed NCT00753545
- Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article PubMed
- HRQoL analysis: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. Epub 2016 Nov 8. link to original article link to PMC article PubMed
- Update: Friedlander M, Matulonis U, Gourley C, du Bois A, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Shirinkin V, Selle F, Fielding A, Lowe ES, McMurtry EL, Spencer S, Rowe P, Mann H, Parry D, Ledermann J. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 2018 Oct;119(9):1075-1085. Epub 2018 Oct 24. link to original article link to PMC article PubMed
- OReO: Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marmé F, Lindemann K, Colombo N, Mądry R, Glasspool R, Vergote I, Korach J, Lheureux S, Dubot C, Oaknin A, Zamagni C, Heitz F, Gladieff L, Rubio-Pérez MJ, Scollo P, Blakeley C, Shaw B, Ray-Coquard I, Redondo A; OReO/ENGOT-ov38 investigators. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023 Dec;34(12):1152-1164. Epub 2023 Oct 4. link to original article contains dosing details in manuscript PubMed NCT03106987
- ICON9: NCT03278717
Rucaparib monotherapy
AIM pathway regimen 2022-08-01 |
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coleman et al. 2017 (ARIEL3) | 2014-2016 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 16.6 vs 5.4 mo (HR 0.23, 95% CI 0.16-0.34) |
Preceding treatment
- Second-line platinum-containing chemotherapy
References
- ARIEL3: Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01968213
- Update: Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. link to original article link to PMC article PubMed
- Update: Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cella D, Meunier J, Goble S, Cameron T, Maloney L, Mörk AC, Bedel J, Ledermann JA, Coleman RL. Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma. J Clin Oncol. 2020 Oct 20;38(30):3494-3505. Epub 2020 Aug 24. link to original article link to PMC article PubMed
- PRO analysis: Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. Epub 2023 May 30. link to original article PubMed
Relapsed or recurrent disease, platinum-resistant
Carboplatin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fotopoulou et al. 2013 (OVATURE) | 2006-2009 | Phase 3 (C) | Carboplatin & Phenoxodiol | Did not meet primary endpoint of PFS |
References
- OVATURE: Fotopoulou C, Vergote I, Mainwaring P, Bidzinski M, Vermorken JB, Ghamande SA, Harnett P, Del Prete SA, Green JA, Spaczynski M, Blagden S, Gore M, Ledermann J, Kaye S, Gabra H. Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study. Ann Oncol. 2014 Jan;25(1):160-5. Epub 2013 Dec 5. link to original article contains dosing details in manuscript PubMed NCT00382811
Niraparib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Moore et al. 2019 (QUADRA) | 2015-2017 | Phase 2 (RT) |
References
- QUADRA: Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. link to original article contains dosing details in abstract PubMed NCT02354586
Olaparib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gelmon et al. 2011 (D0810C00020) | 2008-2009 | Phase 2 |
References
- D0810C00020: Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. Epub 2011 Aug 19. link to original article contains dosing details in manuscript PubMed
Rucaparib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kristeleit et al. 2017 (Study 10) | 2011-2013 | Phase 2 (RT) | ||
Kristeleit et al. 2022 (ARIEL4) | 2017-2020 | Phase 3 (E-switch-ooc) | Standard-of-care chemotherapy | Superior PFS (primary endpoint) Median PFS: 7.4 vs 5.7 mo (HR 0.64, 95% CI 0.49-0.84) |
Note: the OS results of ARIEL4 prompted the withdrawal of this indication for rucaparib.
Biomarker eligibility criteria
- Study 10: Germline BRCA1 or BRCA2 mutation
- ARIEL4: BRCA1 or BRCA2 mutation
References
- Study 10: Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4095-4106. Epub 2017 Mar 6. link to orginal article PubMed NCT01482715
- Pooled subgroup analysis: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. link to original article PubMed
- ARIEL4: Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Apr;23(4):465-478. Epub 2022 Mar 14. link to original article contains dosing details in abstract PubMed NCT02855944
Intraperitoneal therapy
IP Cisplatin & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alberts et al. 1996 (GOG 104) | 1986-1992 | Phase 3 (E-switch-ic) | Cisplatin (IV) & Cyclophosphamide | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IP once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 60 to 90 minutes once on day 1
21-day cycle for 6 cycles
References
- GOG 104: Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B, Adelson MD, Hoskins WJ. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. link to original article contains dosing details in manuscript PubMed