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.

Adenocarcinoma or carcinoma NOS (not otherwise specified)

Bevacizumab (Avastin) & Erlotinib (Tarceva)

Regimen

• Bevacizumab (Avastin) 10 mg/kg IV on days 1 & 15
  • Infusion times for bevacizumab are 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 1-28, 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

Carboplatin (Paraplatin) & Docetaxel (Taxotere)

Regimen #1, Pentheroudakis, et al. 2008

• Carboplatin (Paraplatin) AUC 5 IV over 30 minutes on day 1, given second
• Docetaxel (Taxotere) 75 mg/m2 IV over 30 minutes on day 1, given first

21-day cycles x up to 8 cycles

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 0.1 mg/kg IV prior to chemotherapy

Regimen #2, Greco, et al. 2000

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

21-day cycles x 4-8 cycles

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

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 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 (Paraplatin) & Paclitaxel (Taxol)

Regimen

• Carboplatin (Paraplatin) AUC 6 IV over 30 minutes on day 1, given first
• Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours on day 1, given second

21-day cycles x 6-8 cycles

Supportive medications:

• Methylprednisolone (Solu-Medrol) 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 suggested on days 5-12

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

Carboplatin (Paraplatin), Paclitaxel (Taxol), Etoposide (Vepesid)

Regimen

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

21-day cycles x 4-8 cycles

Supportive medications:

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

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

Carboplatin (Paraplatin), Paclitaxel (Taxol), Gemcitabine (Gemzar)

Regimen

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

21-day cycles

Supportive medications:

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

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

Cisplatin (Platinol) & Docetaxel (Taxotere)

Regimen

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

21-day cycles x up to 8 cycles

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
• 2 liters of normal saline with chemotherapy
• Ondansetron (Zofran) 32 mg IV or Granisetron (Kytril) 10 mcg/kg IV 15 minutes prior to cisplatin
• Ondansetron (Zofran) 8 mg PO TID on days 2-6

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 verified protocol PubMed

Cisplatin (Platinol), Etoposide (Vepesid), Bleomycin (Blenoxane)

Regimen

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

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

Cisplatin (Platinol) & Gemcitabine (Gemzar)

Regimen

• Cisplatin (Platinol) 100 mg/m2 IV on day 1
• Gemcitabine (Gemzar) 1250 mg/m2 IV 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 (Platinol) & Irinotecan (Camptosar)

Regimen

• Cisplatin (Platinol) 80 mg/m2 IV on day 1
• Irinotecan (Camptosar) 150 mg/m2 IV 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

Gemcitabine (Gemzar) & Docetaxel (Taxotere)

Regimen

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

21-day cycles x up to 6 cycles

Supportive medications:

• Corticosteroids PO the day before, the day of, and day after docetaxel

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

Squamous cell carcinoma

Cisplatin (Platinol), Docetaxel (Taxotere), Fluorouracil (5-FU)

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.

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

21-day cycles x 3 cycles

Supportive medications:

• 1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate
• Dexamethasone (Decadron) 8 mg PO daily 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 5-15

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 (Platinol), Paclitaxel (Taxol), Fluorouracil (5-FU)

Regimen

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.

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

21-day cycles x 3 cycles

Supportive medications:

• Dexamethasone (Decadron), Diphenhydramine (Benadryl), and Cimetidine (Tagamet) or Ranitidine (Zantac) 30 minutes before paclitaxel

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.