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


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.

ESMO

NCCN

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

21-day cycles

References

  1. 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

Supportive therapy

21-day cycle for up to 8 cycles


Regimen variant #2

Study Evidence
Greco et al. 2000 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for 4 to 8 cycles

References

  1. 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
  2. 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 & Gemcitabine (GCb) & Paclitaxel

GCP: Gemcitabine, Carboplatin, Paclitaxel

Regimen

Study Evidence
Greco et al. 2002 Phase 2

Chemotherapy

Supportive therapy

21-day cycles

References

  1. 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

Carboplatin & Paclitaxel (CP)

Regimen

Study Evidence
Briasoulis et al. 2000 Phase 2
Hayashi et al. 2019 Phase 2

Chemotherapy

Supportive therapy

per Briasoulis 2000 study

21-day cycle for 6 to 8 cycles

References

  1. 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
  2. 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.

Chemotherapy

21-day cycles

References

  1. 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 NCT00126269

Cisplatin & Docetaxel (DC)

Regimen

Study Evidence
Greco et al. 2000 Phase 2

Chemotherapy

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) 8 mg PO three times per day on days 2 to 6

21-day cycle for up to 8 cycles

References

  1. 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

21-day cycles

References

  1. 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
  2. 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 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

21-day cycles

References

  1. 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

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

  1. None that we are aware of

Docetaxel & Gemcitabine

Regimen

Study Evidence
Pouessel et al. 2004 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles

References

  1. 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

  1. 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

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

21-day cycle for up to 6 cycles

References

  1. 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

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

Supportive therapy

21-day cycle for 4 to 8 cycles

References

  1. 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
  2. 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

21-day cycle for 3 cycles

References

  1. None that we are aware of
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