Difference between revisions of "Carcinoma of unknown primary"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | Carcinoma of unknown primary may also be referred to as carcinoma of unknown primary site, cancer/carcinoma of unknown primary (CUP), occult primary, or unknown primary carcinoma. | |
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{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div> | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] 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}} 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> |
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==[https://www.asco.org/ ASCO]== | ||
+ | *'''2020:''' Maghami et al. [https://doi.org/10.1200/jco.20.00275 Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/32324430/ PubMed] | ||
− | + | ==[https://www.esmo.org/ ESMO]== | |
− | ==[ | + | *'''2023:''' Krämer et al. [https://doi.org/10.1016/j.annonc.2022.11.013 Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/36563965 PubMed] |
− | *[ | + | **'''2015:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdv305 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/26314775 PubMed] |
+ | **'''2011:''' Fizazi et al. [https://doi.org/10.1093/annonc/mdr389 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/21908507 PubMed] | ||
+ | **'''2010:''' Pavlidis et al. [https://doi.org/10.1093/annonc/mdq193 Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555087 PubMed] | ||
+ | **'''2009:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdp159 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454441 PubMed] | ||
+ | **'''2008:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdn104 Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456742 PubMed] | ||
+ | **'''2007:''' [https://doi.org/10.1093/annonc/mdm049 Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491060 PubMed] | ||
+ | **'''2005:''' Briasoulis et al. [https://doi.org/10.1093/annonc/mdi804 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)] [https://pubmed.ncbi.nlm.nih.gov/15888766 PubMed] | ||
+ | **'''2001:''' [https://doi.org/10.1023/a:1017409423484 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)] [https://pubmed.ncbi.nlm.nih.gov/11583184 PubMed] | ||
− | ==[https://www.nccn.org/ NCCN] | + | ==NCCN== |
− | *[https:// | + | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1451 NCCN Guidelines - Occult Primary] |
+ | **'''2014:''' Ettinger et al. [https://doi.org/10.6004/jnccn.2014.0093 Occult Primary, Version 3.2014] [https://pubmed.ncbi.nlm.nih.gov/24994917/ PubMed] | ||
+ | **'''2011:''' Ettinger et al. [https://doi.org/10.6004/Jnccn.2011.0117 NCCN Clinical Practice Guidelines Occult primary.] [https://pubmed.ncbi.nlm.nih.gov/22157556/ PubMed] | ||
+ | **'''2005:''' Ettinger et al. Occult primary cancer clinical practice guidelines. [https://pubmed.ncbi.nlm.nih.gov/19817031/ PubMed] | ||
=All lines of therapy= | =All lines of therapy= | ||
− | + | ==BEP {{#subobject:cc3566|Regimen=1}}== | |
− | == | + | BEP: '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin) |
− | + | <br>PEB: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>B</u>'''leomycin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
===Regimen {{#subobject:953c7d|Variant=1}}=== | ===Regimen {{#subobject:953c7d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !Study | + | !style="width: 33%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1992.10.6.912 Hainsworth et al 1992] |
− | |style="background-color:#91cf61"|Phase | + | |1978-02 to 1989-12 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Bleomycin (Blenoxane)]] 30 units IV once per day on days 1, 8, 15 | *[[Bleomycin (Blenoxane)]] 30 units IV once per day on days 1, 8, 15 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. [ | + | # Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. [https://doi.org/10.1200/jco.1992.10.6.912 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1375284/ PubMed] |
− | |||
==Carboplatin & Docetaxel {{#subobject:44b3f6|Regimen=1}}== | ==Carboplatin & Docetaxel {{#subobject:44b3f6|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:88482c|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/10.1080/02841860701843043 Pentheroudakis et al. 2008] | |
− | + | |2000-01 to NR | |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |||
− | |||
− | |||
− | |||
− | |[https:// | ||
− | |style="background-color:#91cf61"|Phase | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given second''' | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given second''' | ||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1, '''given first''' | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on day -1, then 16 mg IV once on day 1, '''prior to chemotherapy''' |
− | *[[Dexamethasone (Decadron)]] 8 mg PO | + | *[[Ondansetron (Zofran)]] 8 mg IV once on day 1, '''prior to chemotherapy''' |
− | + | *[[Ranitidine (Zantac)]] 100 mg IV once on day 1, '''prior to chemotherapy''' | |
− | *[[Ondansetron (Zofran)]] 8 mg IV prior to chemotherapy | + | *[[Dimetindene (Fenistil)]] 0.1 mg/kg (route unclear) prior to chemotherapy |
− | *[[Ranitidine (Zantac)]] 100 mg IV prior to chemotherapy | ||
− | *[[ | ||
− | |||
'''21-day cycle for up to 8 cycles''' | '''21-day cycle for up to 8 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen #2 {{#subobject:a56594|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2 {{#subobject:a56594|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000 Study A] |
− | |style="background-color:#91cf61"|Phase | + | |1996-11 to 1997-08 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 20 minutes once on day 1, '''given second''' | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 20 minutes once on day 1, '''given second''' | ||
*[[Docetaxel (Taxotere)]] 65 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | *[[Docetaxel (Taxotere)]] 65 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 |
− | *[[Dexamethasone (Decadron)]] 8 mg PO | + | *One of the following serotonin 5-HT3 antagonists: |
− | *[[Ondansetron (Zofran)]] 32 mg IV | + | **[[Ondansetron (Zofran)]] 32 mg IV once on day 1; 15 minutes prior to chemotherapy |
− | + | **[[Granisetron]] 10 mcg/kg IV once on day 1; 15 minutes prior to chemotherapy | |
'''21-day cycle for 4 to 8 cycles''' | '''21-day cycle for 4 to 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211 | + | # Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10761758/ PubMed] |
− | # Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. [https:// | + | # Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. [https://doi.org/10.1080/02841860701843043 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18607872/ PubMed] |
− | + | ==Carboplatin & Gemcitabine (GCb) & Paclitaxel {{#subobject:4d259f|Regimen=1}}== | |
− | ==Carboplatin | + | GCP: '''<u>G</u>'''emcitabine, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:96f90f|Variant=1}}=== | ===Regimen {{#subobject:96f90f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !Study | + | !style="width: 33%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2002.20.6.1651 Greco et al. 2002] |
− | |style="background-color:#91cf61"|Phase | + | |1998-12 to 2000-08 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 20 to 30 minutes once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 20 to 30 minutes once on day 1 | ||
− | |||
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[:Category:Steroids|Corticosteroids]] IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[:Category:Steroids|Corticosteroids]] IV 30 minutes prior to | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV 30 minutes prior to | + | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. [ | + | # Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. [https://doi.org/10.1200/jco.2002.20.6.1651 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11896116/ PubMed] |
− | ==Carboplatin & Paclitaxel {{#subobject:910bdc|Regimen=1}}== | + | ==Carboplatin & Paclitaxel (CP) {{#subobject:910bdc|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:a386ae|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/10.1200/jco.2000.18.17.3101 Briasoulis et al. 2000] |
− | | | + | |1996-02 to 1999-02 |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.18.00771 Hayashi et al. 2019] |
− | |style="background-color:#91cf61"|Phase | + | |2008-10 to 2015-02 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1, '''given first''' | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1, '''given first''' | ||
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second''' | *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | per Briasoulis 2000 study |
− | *[[Methylprednisolone (Solumedrol)]] 32 mg PO 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin | + | *[[Methylprednisolone (Solumedrol)]] 32 mg PO for three doses, 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin |
− | *[[Dexamethasone (Decadron)]] 16 mg IV | + | *[[Dexamethasone (Decadron)]] 16 mg IV once on day 1, at least 10 minutes prior to chemotherapy |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV | + | *One of the following antihistamines: |
− | *[[Ranitidine (Zantac)]] 100 mg IV | + | **[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1, at least 10 minutes prior to chemotherapy |
− | *[[Ondansetron (Zofran)]] 8 mg IV after the above premedications | + | **[[Dimetindene (Fenistil)]] 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy |
− | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day | + | *[[Ranitidine (Zantac)]] 100 mg IV once on day 1, at least 10 minutes prior to chemotherapy |
− | + | *[[Ondansetron (Zofran)]] 8 mg IV once on day 1, after the above premedications | |
+ | *Suggested: [[Filgrastim (Neupogen)]] 300 mcg SC once per day on days 5 to 12 | ||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. [ | + | # Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. [https://doi.org/10.1200/jco.2000.18.17.3101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963638/ PubMed] |
+ | # Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, Minami H, Toyoda M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Ohashi Y, Nishio K, Nakagawa K. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. J Clin Oncol. 2019 Mar 1;37(7):570-579. Epub 2019 Jan 17. [https://doi.org/10.1200/jco.18.00771 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30653423/ PubMed] | ||
==Cisplatin monotherapy {{#subobject:21015c|Regimen=1}}== | ==Cisplatin monotherapy {{#subobject:21015c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a5832e|Variant=1}}=== | ===Regimen {{#subobject:a5832e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2012.01.011 Gross-Goupil et al. 2012 (GEFCAPI 02)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2003-2007 |
− | |[[#Cisplatin_. | + | |style="background-color:#1a9851"|Randomized Phase 2 (C) |
− | |style="background-color:#ffffbf"| | + | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <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 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [ | + | # '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://doi.org/10.1016/j.ejca.2012.01.011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22317952/ PubMed] [https://clinicaltrials.gov/study/NCT00126269 NCT00126269] |
− | + | ==Cisplatin & Docetaxel (DC) {{#subobject:27937b|Regimen=1}}== | |
− | ==Cisplatin & Docetaxel {{#subobject:27937b|Regimen=1}}== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:61bedc|Variant=1}}=== | ===Regimen {{#subobject:61bedc|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !Study | + | !style="width: 33%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1023/a:1008369812295 Greco et al. 2000 Study B] |
− | |style="background-color:#91cf61"|Phase | + | |1997-09 to 1998-10 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 |
− | *[[Dexamethasone (Decadron)]] 8 mg PO | + | **Suggested: 20 mg IV once on day 1; 15 minutes prior to cisplatin |
− | *Suggested: | ||
*2 liters of normal saline with chemotherapy | *2 liters of normal saline with chemotherapy | ||
− | *[[Ondansetron (Zofran)]] 32 mg IV | + | *One of the following serotonin 5-HT3 antagonists: |
− | *[[Ondansetron (Zofran)]] 8 mg PO | + | **[[Ondansetron (Zofran)]] 32 mg IV once on day 1; 15 minutes prior to cisplatin |
− | + | **[[Granisetron]] 10 mcg/kg IV once on day 1; 15 minutes prior to cisplatin | |
+ | *[[Ondansetron (Zofran)]] 8 mg PO three times per day on days 2 to 6 | ||
'''21-day cycle for up to 8 cycles''' | '''21-day cycle for up to 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211 | + | # Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. [https://doi.org/10.1023/a:1008369812295 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10761758/ PubMed] |
− | ==Cisplatin & Gemcitabine {{#subobject:a36533|Regimen=1}}== | + | ==Cisplatin & Gemcitabine (GC) {{#subobject:a36533|Regimen=1}}== |
− | + | GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
===Regimen {{#subobject:2506f|Variant=1}}=== | ===Regimen {{#subobject:2506f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.12.104 Culine et al. 2003 (GEFCAPI 01)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |1999-2000 |
− | |[[#Cisplatin_. | + | |style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic) |
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2012.01.011 Gross-Goupil et al. 2012 (GEFCAPI 02)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2003-2007 |
+ | |style="background-color:#1a9851"|Randomized Phase 2 (E-esc) | ||
|[[#Cisplatin_monotherapy|Cisplatin]] | |[[#Cisplatin_monotherapy|Cisplatin]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of 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 | ||
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [ | + | # '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12972523/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [ | + | # '''GEFCAPI 02:''' Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. [https://doi.org/10.1016/j.ejca.2012.01.011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22317952/ PubMed] [https://clinicaltrials.gov/study/NCT00126269 NCT00126269] |
− | + | ==Cisplatin & Irinotecan (IC) {{#subobject:a7a736|Regimen=1}}== | |
− | ==Cisplatin & Irinotecan {{#subobject:a7a736|Regimen=1}}== | + | IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''isplatin |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:3940e6|Variant=1}}=== | ===Regimen {{#subobject:3940e6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.12.104 Culine et al. 2003 (GEFCAPI 01)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |1999-2000 |
− | |[[#Cisplatin_. | + | |style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic) |
+ | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1 | *[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # '''GEFCAPI 01:''' Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. [https://doi.org/10.1200/jco.2003.12.104 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12972523/ PubMed] | ||
+ | ==DCF {{#subobject:3f05e4|Regimen=1}}== | ||
+ | DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:2ae092|Variant=1}}=== | ||
+ | ''Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m<sup>2</sup>) | ||
+ | ====Supportive therapy==== | ||
+ | *1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate | ||
+ | *[[Dexamethasone (Decadron)]] 8 mg PO once per day the day before, the day of, and day after chemotherapy | ||
+ | *[[Ciprofloxacin (Cipro)]] 1000 mg PO (reference did not specify, but assume 500 mg twice per day) on days 5 to 15 | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # None that we are aware of |
− | |||
==Docetaxel & Gemcitabine {{#subobject:d61b91|Regimen=1}}== | ==Docetaxel & Gemcitabine {{#subobject:d61b91|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a67a4e|Variant=1}}=== | ===Regimen {{#subobject:a67a4e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !Study | + | !style="width: 33%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1002/cncr.20100 Pouessel et al. 2004] |
− | |style="background-color:#91cf61"|Phase | + | |2000-12 to 2003-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8 | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[:Category:Steroids|Corticosteroids]] PO the day before, the day of, and day after docetaxel |
− | *[[:Category:Steroids|Corticosteroids]] PO the day before, the day of, and day after | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. [ | + | # Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. [https://doi.org/10.1002/cncr.20100 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15022294/ PubMed] |
− | |||
==Erlotinib & Bevacizumab {{#subobject:742957|Regimen=1}}== | ==Erlotinib & Bevacizumab {{#subobject:742957|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e0f611|Variant=1}}=== | ===Regimen {{#subobject:e0f611|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !Study | + | !style="width: 33%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.09.3047 Hainsworth et al. 2007a] |
− | |style="background-color:#91cf61"|Phase | + | |2004-04 to 2005-07 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Erlotinib (Tarceva)]] 150 mg PO on days 1 to 28 | + | ====Targeted therapy==== |
+ | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28 | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15 | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15 | ||
**Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later | **Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. [ | + | # Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. [https://doi.org/10.1200/jco.2006.09.3047 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17470864/ PubMed] |
− | |||
==Gemcitabine & Irinotecan {{#subobject:3f6501|Regimen=1}}== | ==Gemcitabine & Irinotecan {{#subobject:3f6501|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:6a2c02|Variant=1}}=== | ===Regimen {{#subobject:6a2c02|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1097/ppo.0b013e3181c6aa89 Hainsworth et al. 2010 (SCRI UNKPRI 12)] |
− | |style="background-color:#1a9851"|Phase | + | |2003-2008 |
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
|[[#PCE|PCE]] | |[[#PCE|PCE]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS24 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
*[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SCRI UNKPRI 12:''' Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [https://doi.org/10.1097/ppo.0b013e3181c6aa89 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695/ PubMed] [https://clinicaltrials.gov/study/NCT00193596 NCT00193596] | ||
+ | ==Nivolumab monotherapy {{#subobject:3fni01|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ni2c02|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.annonc.2021.11.009 Tanizaki et al. 2021] | ||
+ | |2018-02-19 to 2019-08-09 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This was the trial supporting PMDA approval for this indication.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Immunotherapy==== | ||
+ | *[[Nivolumab (Opdivo)]] 240 mg IV once on day 1 | ||
+ | '''14-day cycle for up to 52 cycles (2 years)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226. Epub 2021 Nov 26. [https://doi.org/10.1016/j.annonc.2021.11.009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34843940/ PubMed] UMIN000030649 |
==PCE {{#subobject:87de5a|Regimen=1}}== | ==PCE {{#subobject:87de5a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:886058|Variant=1}}=== | ===Regimen {{#subobject:886058|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9 Greco et al. 2000a] |
− | |style="background-color:#91cf61"|Phase | + | |1995-1996 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1097/ppo.0b013e3181c6aa89 Hainsworth et al. 2010 (SCRI UNKPRI 12)] |
− | |style="background-color:#1a9851"|Phase | + | |2003-2008 |
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
|[[#Gemcitabine_.26_Irinotecan|Gemcitabine & Irinotecan]] | |[[#Gemcitabine_.26_Irinotecan|Gemcitabine & Irinotecan]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS24 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
Line 380: | Line 428: | ||
**Days 1, 3, 5, 7, 9: 50 mg PO once per day | **Days 1, 3, 5, 7, 9: 50 mg PO once per day | ||
**Days 2, 4, 6, 8, 10: 100 mg PO once per day | **Days 2, 4, 6, 8, 10: 100 mg PO once per day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 20 mg PO for two doses, 12 hours and 4 hours prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg PO 12 hours and 4 hours prior to | + | *[[Dexamethasone (Decadron)]] 20 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg IV 30 minutes prior to | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV 30 minutes prior to | + | *[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel |
− | *[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to | ||
− | |||
'''21-day cycle for 4 to 8 cycles''' | '''21-day cycle for 4 to 8 cycles''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. [https://doi.org/10.1002/1097-0142%2820001215%2989:12%3C2655::AID-CNCR19%3E3.0.CO;2-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11135228/ PubMed] | ||
+ | # '''SCRI UNKPRI 12:''' Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. [https://doi.org/10.1097/ppo.0b013e3181c6aa89 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20164695/ PubMed] [https://clinicaltrials.gov/study/NCT00193596 NCT00193596] | ||
+ | ==PCF {{#subobject:71face|Regimen=1}}== | ||
+ | PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:c82ab5|Variant=1}}=== | ||
+ | ''Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1 | ||
+ | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 2500 mg/m<sup>2</sup>) | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # None that we are aware of |
− | + | [[Category:Carcinoma of unknown primary regimens]] | |
− | + | [[Category:Site-agnostic regimens]] | |
− | [[Category: | + | [[Category:Malignant solid neoplasm]] |
Latest revision as of 12:21, 15 July 2024
Carcinoma of unknown primary may also be referred to as carcinoma of unknown primary site, cancer/carcinoma of unknown primary (CUP), occult primary, or unknown primary carcinoma.
15 regimens on this page
16 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2020: Maghami et al. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline PubMed
ESMO
- 2023: Krämer et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2015: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2011: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Pavlidis et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up PubMed
- 2007: Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Briasoulis et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) PubMed
NCCN
- NCCN Guidelines - Occult Primary
- 2014: Ettinger et al. Occult Primary, Version 3.2014 PubMed
- 2011: Ettinger et al. NCCN Clinical Practice Guidelines Occult primary. PubMed
- 2005: Ettinger et al. Occult primary cancer clinical practice guidelines. PubMed
All lines of therapy
BEP
BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PEB: Platinol (Cisplatin), Etoposide, Bleomycin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hainsworth et al 1992 | 1978-02 to 1989-12 | Phase 2 |
Chemotherapy
- Bleomycin (Blenoxane) 30 units IV once per day on days 1, 8, 15
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
21-day cycles
References
- Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Docetaxel
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Pentheroudakis et al. 2008 | 2000-01 to NR | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
- Docetaxel (Taxotere) 75 mg/m2 IV over 30 minutes once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO twice per day on day -1, then 16 mg IV once on day 1, prior to chemotherapy
- Ondansetron (Zofran) 8 mg IV once on day 1, prior to chemotherapy
- Ranitidine (Zantac) 100 mg IV once on day 1, prior to chemotherapy
- Dimetindene (Fenistil) 0.1 mg/kg (route unclear) prior to chemotherapy
21-day cycle for up to 8 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Greco et al. 2000 Study A | 1996-11 to 1997-08 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 20 minutes once on day 1, given second
- Docetaxel (Taxotere) 65 mg/m2 IV over 60 minutes once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
- One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to chemotherapy
- Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to chemotherapy
21-day cycle for 4 to 8 cycles
References
- Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Gemcitabine (GCb) & Paclitaxel
GCP: Gemcitabine, Carboplatin, Paclitaxel
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Greco et al. 2002 | 1998-12 to 2000-08 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Carboplatin (Paraplatin) AUC 5 IV over 20 to 30 minutes once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- Corticosteroids IV once on day 1; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycles
References
- Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Paclitaxel (CP)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Briasoulis et al. 2000 | 1996-02 to 1999-02 | Phase 2 |
Hayashi et al. 2019 | 2008-10 to 2015-02 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given first
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given second
Supportive therapy
per Briasoulis 2000 study
- Methylprednisolone (Solumedrol) 32 mg PO for three doses, 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin
- Dexamethasone (Decadron) 16 mg IV once on day 1, at least 10 minutes prior to chemotherapy
- One of the following antihistamines:
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, at least 10 minutes prior to chemotherapy
- Dimetindene (Fenistil) 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy
- Ranitidine (Zantac) 100 mg IV once on day 1, at least 10 minutes prior to chemotherapy
- Ondansetron (Zofran) 8 mg IV once on day 1, after the above premedications
- Suggested: Filgrastim (Neupogen) 300 mcg SC once per day on days 5 to 12
21-day cycle for 6 to 8 cycles
References
- Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, Minami H, Toyoda M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Ohashi Y, Nishio K, Nakagawa K. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. J Clin Oncol. 2019 Mar 1;37(7):570-579. Epub 2019 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gross-Goupil et al. 2012 (GEFCAPI 02) | 2003-2007 | Randomized Phase 2 (C) | Cisplatin & Gemcitabine | Did not meet primary endpoint of OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
References
- GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00126269
Cisplatin & Docetaxel (DC)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Greco et al. 2000 Study B | 1997-09 to 1998-10 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
- Suggested: 20 mg IV once on day 1; 15 minutes prior to cisplatin
- 2 liters of normal saline with chemotherapy
- One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to cisplatin
- Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to cisplatin
- Ondansetron (Zofran) 8 mg PO three times per day on days 2 to 6
21-day cycle for up to 8 cycles
References
- Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine & Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Culine et al. 2003 (GEFCAPI 01) | 1999-2000 | Randomized Phase 2 (E-switch-ic) | Cisplatin & Irinotecan | Not reported |
Gross-Goupil et al. 2012 (GEFCAPI 02) | 2003-2007 | Randomized Phase 2 (E-esc) | Cisplatin | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00126269
Cisplatin & Irinotecan (IC)
IC: Irinotecan & Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Culine et al. 2003 (GEFCAPI 01) | 1999-2000 | Randomized Phase 2 (E-switch-ic) | Cisplatin & Gemcitabine | Not reported |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
21-day cycles
References
- GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
DCF
DCF: Docetaxel, Cisplatin, Fluorouracil
Regimen
Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 750 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m2)
Supportive therapy
- 1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate
- Dexamethasone (Decadron) 8 mg PO once per day the day before, the day of, and day after chemotherapy
- Ciprofloxacin (Cipro) 1000 mg PO (reference did not specify, but assume 500 mg twice per day) on days 5 to 15
21-day cycle for 3 cycles
References
- None that we are aware of
Docetaxel & Gemcitabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Pouessel et al. 2004 | 2000-12 to 2003-04 | Phase 2 |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
Supportive therapy
- Corticosteroids PO the day before, the day of, and day after docetaxel
21-day cycle for up to 6 cycles
References
- Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Erlotinib & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hainsworth et al. 2007a | 2004-04 to 2005-07 | Phase 2 |
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
- Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
28-day cycles
References
- Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Gemcitabine & Irinotecan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hainsworth et al. 2010 (SCRI UNKPRI 12) | 2003-2008 | Phase 3 (E-switch-ic) | PCE | Did not meet primary endpoint of OS24 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 100 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
References
- SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article PubMed NCT00193596
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Tanizaki et al. 2021 | 2018-02-19 to 2019-08-09 | Phase 2 (RT) |
Note: This was the trial supporting PMDA approval for this indication.
References
- Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226. Epub 2021 Nov 26. link to original article PubMed UMIN000030649
PCE
PCE: Paclitaxel, Carboplatin, Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Greco et al. 2000a | 1995-1996 | Phase 2 | ||
Hainsworth et al. 2010 (SCRI UNKPRI 12) | 2003-2008 | Phase 3 (E-switch-ic) | Gemcitabine & Irinotecan | Did not meet primary endpoint of OS24 |
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 60 minutes once on day 1
- Carboplatin (Paraplatin) AUC 6 IV over 20 to 30 minutes once on day 1
- Etoposide (Vepesid) as follows:
- Days 1, 3, 5, 7, 9: 50 mg PO once per day
- Days 2, 4, 6, 8, 10: 100 mg PO once per day
Supportive therapy
- Dexamethasone (Decadron) 20 mg PO for two doses, 12 hours and 4 hours prior to paclitaxel
- Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycle for 4 to 8 cycles
References
- Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article PubMed NCT00193596
PCF
PCF: Paclitaxel, Cisplatin, Fluorouracil
Regimen
Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 2500 mg/m2)
21-day cycle for 3 cycles
References
- None that we are aware of