Carcinoma of unknown primary

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Unknown primary tumor may also be referred to as carcinoma of unknown primary site, cancer of unknown primary (CUP), occult primary, or unknown primary carcinoma.

15 regimens on this page 16 variants on this page

Adenocarcinoma or carcinoma NOS (not otherwise specified)

Bevacizumab & Erlotinib

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Regimen

Study	Evidence
Hainsworth et al. 2007	Phase II

Chemotherapy

• 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
• Erlotinib (Tarceva) 150 mg PO on days 1 to 28, 1 hour before or 2 hours after meals

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 verified protocol PubMed

Bleomycin, Cisplatin, Etoposide

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Regimen

Study	Evidence
Hainsworth et al 1992	Phase II

Chemotherapy

• Bleomycin (Blenoxane) 30 units IV once per day on days 1, 8, 15
• Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5

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 verified protocol PubMed

Carboplatin & Docetaxel

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Regimen #1

Study	Evidence
Pentheroudakis et al. 2008	Phase II

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 medications

• Dexamethasone (Decadron) 8 mg PO BID the day before chemotherapy
• Dexamethasone (Decadron) 16 mg IV prior to chemotherapy, on the day of chemotherapy
• Ondansetron (Zofran) 8 mg IV prior to chemotherapy
• Ranitidine (Zantac) 100 mg IV prior to chemotherapy
• Dimethindene maleate (Fenestil) 0.1 mg/kg (route unclear) prior to chemotherapy

21-day cycle for up to 8 cycles

Regimen #2

Study	Evidence
Greco et al. 2000	Phase II

Chemotherapy

• Carboplatin (Paraplatin) AUC 6 IV over 20 minutes once on day 1, given second
• Docetaxel (Taxotere) 65 mg/m² IV over 1 hour once on day 1, given first

Supportive medications

• Dexamethasone (Decadron) 8 mg PO BID the day before, the day of, and day after chemotherapy
• Ondansetron (Zofran) 32 mg IV or Granisetron (Kytril) 10 mcg/kg IV 15 minutes prior to chemotherapy

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 to 5. link to original article contains verified protocol 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 verified protocol PubMed

Carboplatin, Gemcitabine, Paclitaxel

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Regimen

Study	Evidence
Greco et al. 2002	Phase II

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 IV over 20 to 30 minutes once on day 1
• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
• Paclitaxel (Taxol) 200 mg/m² IV over 1 hour once on day 1

Supportive medications

• Corticosteroids IV 30 minutes prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to Paclitaxel (Taxol)
• Cimetidine (Tagamet) 300 mg IV 30 minutes prior to Paclitaxel (Taxol)

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 verified protocol PubMed

Carboplatin & Paclitaxel

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Regimen

Study	Evidence
Briasoulis et al. 2000	Phase II

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 medications

• Methylprednisolone (Solumedrol) 32 mg PO 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin
• Dexamethasone (Decadron) 16 mg IV over 10 minutes prior to chemotherapy
• Diphenhydramine (Benadryl) 50 mg IV or dimethindene maleate 0.1 mg/kg IV over 10 minutes prior to chemotherapy
• Ranitidine (Zantac) 100 mg IV over 10 minutes prior to chemotherapy
• Ondansetron (Zofran) 8 mg IV after the above premedications
• Filgrastim (Neupogen) 300 mcg SC once per day suggested on days 5 to 12

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. 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 verified protocol PubMed

Cisplatin (Platinol)

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Regimen

Study	Evidence	Comparator
Gross-Goupil et al. 2012 (GEFCAPI 02)	Randomized Phase II	Cisplatin & Gemcitabine

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1

21-day cycles

References

1. 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 verified protocol PubMed

Cisplatin & Docetaxel

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Regimen

Study	Evidence
Greco et al. 2000	Phase II

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV over 1 hour once on day 1
• Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1

Supportive medications

• Dexamethasone (Decadron) 8 mg PO BID the day before, the day of, and day after chemotherapy
• Suggested: Dexamethasone (Decadron) 20 mg IV 15 minutes prior to Cisplatin (Platinol)
• 2 liters of normal saline with chemotherapy
• Ondansetron (Zofran) 32 mg IV or Granisetron (Kytril) 10 mcg/kg IV 15 minutes prior to Cisplatin (Platinol)
• Ondansetron (Zofran) 8 mg PO TID 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 to 5. link to original article contains verified protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study	Evidence	Comparator
Culine et al. 2003 (GEFCAPI 01)	Randomized Phase II	Cisplatin & Irinotecan
Gross-Goupil et al. 2012 (GEFCAPI 02)	Randomized Phase II	Cisplatin

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

1. 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 verified protocol PubMed content property of HemOnc.org
2. 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 verified protocol PubMed

Cisplatin & Irinotecan

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Regimen

Study	Evidence	Comparator
Culine et al. 2003 (GEFCAPI 01)	Randomized Phase II	Cisplatin & Gemcitabine

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

1. 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 verified protocol PubMed

Docetaxel & Gemcitabine

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Regimen

Study	Evidence
Pouessel et al. 2004	Phase II

Chemotherapy

• Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 8
• Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8

Supportive medications

• Corticosteroids PO the day before, the day of, and day after Docetaxel (Taxotere)

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 verified protocol PubMed

Gemcitabine & Irinotecan

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Regimen

Study	Evidence	Comparator
Hainsworth et al. 2010	Phase III	PCE

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

1. 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

PCE

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PCE: Paclitaxel, Carboplatin, Etoposide

Regimen

Study	Evidence	Comparator
Greco et al. 2000	Phase II
Hainsworth et al. 2010	Phase III	Gemcitabine & Irinotecan

Chemotherapy

• Paclitaxel (Taxol) 200 mg/m² IV over 1 hour once on day 1
• Carboplatin (Paraplatin) AUC 6 IV over 20 to 30 minutes once on day 1
• Etoposide (Vepesid) 50 mg PO once per day on days 1, 3, 5, 7, 9, and 100 mg PO once per day on days 2, 4, 6, 8, 10

Supportive medications

• Dexamethasone (Decadron) 20 mg PO 12 hours and 4 hours prior to Paclitaxel (Taxol)
• Dexamethasone (Decadron) 20 mg IV 30 minutes prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to Paclitaxel (Taxol)
• Cimetidine (Tagamet) 300 mg IV 30 minutes prior to Paclitaxel (Taxol)

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 verified protocol PubMed
2. 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

Squamous cell carcinoma

Cisplatin, Docetaxel, Fluorouracil

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Regimen

The NCCN, Occult Primary version 1.2012 lists this as a suitable regimen in this setting. The Pointreau et al. 2009 regimen was for larynx and hypopharynx cancer, and the regimen also involved chemoradiation +/- surgery.

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV once on day 1
• Docetaxel (Taxotere) 75 mg/m² IV once on day 1
• Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5

Supportive medications

• 1 liter normal saline before and after Cisplatin (Platinol) +/- 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 BID) on days 5 to 15

21-day cycle for 3 cycles

References

1. Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. link to original article contains verified protocol--see comment above PubMed

Cisplatin, Fluorouracil, Paclitaxel

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Regimen

Note: The NCCN, Occult Primary version 1.2012 lists this as a suitable regimen in this setting. The Hitt et al. 2005 regimen was for head and neck cancer, and the regimen also involved chemoradiation.

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 2
• Fluorouracil (5-FU) 500 mg/m²/day IV continuous infusion over 120 hours on days 2 to 6
• Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive medications

• Dexamethasone (Decadron) 30 minutes before Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 30 minutes before Paclitaxel (Taxol)
• Cimetidine (Tagamet) or Ranitidine (Zantac) 30 minutes before Paclitaxel (Taxol)

21-day cycle for 3 cycles

References

1. Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005 Dec 1;23(34):8636-45. Epub 2005 Nov 7. link to original article contains verified protocol--see comment above PubMed

Neuroendocrine tumors

• Poorly differentiated or small cell tumors can be treated with small cell lung cancer regimens.
• Moderate to well-differentiated neuroendocrine tumors can be treated with regimens for neuroendocrine tumors.