Carcinoma of unknown primary
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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.
14 regimens on this page
15 variants on this page
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Guidelines
ESMO
- 2023: Krämer et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Older
- 2015: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- 2011: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- 2010: Pavlidis et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- 2009: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up
- 2008: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up
- 2007: Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up
- 2005: Briasoulis et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)
NCCN
Older
- 2014: Ettinger et al. Occult Primary, Version 3.2014 PubMed
All lines of therapy
BEP
BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PEB: Platinol (Cisplatin), Etoposide, Bleomycin
Regimen
| Study | Evidence |
|---|---|
| Hainsworth et al 1992 | 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 contains dosing details in manuscript PubMed
Carboplatin & Docetaxel
Regimen variant #1
| Study | Evidence |
|---|---|
| Pentheroudakis et al. 2008 | 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 | Evidence |
|---|---|
| Greco et al. 2000 | 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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed
Carboplatin & Paclitaxel (CP)
Regimen
| Study | Evidence |
|---|---|
| Briasoulis et al. 2000 | Phase 2 |
| Hayashi et al. 2019 | 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 contains dosing details in manuscript 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. link to original article contains dosing details in manuscript 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 contains dosing details in manuscript PubMed Clinical Trial Registry
Cisplatin & Docetaxel (DC)
Regimen
| Study | Evidence |
|---|---|
| Greco et al. 2000 | 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed Clinical Trial Registry
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 contains dosing details in manuscript 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 | Evidence |
|---|---|
| Pouessel et al. 2004 | 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 contains dosing details in manuscript PubMed
Erlotinib & Bevacizumab
Regimen
| Study | Evidence |
|---|---|
| Hainsworth et al. 2007a | Phase 2 |
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
- 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 contains dosing details in manuscript PubMed
GCP
GCP: Gemcitabine, Carboplatin, Paclitaxel
Regimen
| Study | Evidence |
|---|---|
| Greco et al. 2002 | 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 contains dosing details in manuscript 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 Clinical Trial Registry
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 contains dosing details in manuscript 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 Clinical Trial Registry
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