Carcinoma of unknown primary

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Adenocarcinoma 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

ESMO

• Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2015) PubMed

NCCN

• NCCN Guidelines - Occult Primary (Cancer of Unknown Primary (CUP))

All lines of therapy

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 60 minutes 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 60 minutes 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 monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Gross-Goupil et al. 2012 (GEFCAPI 02)	Randomized Phase II	Cisplatin & Gemcitabine	Seems not superior

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 60 minutes once on day 1
• Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes 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	Efficacy
Culine et al. 2003 (GEFCAPI 01)	Randomized Phase II	Cisplatin & Irinotecan	Not reported
Gross-Goupil et al. 2012 (GEFCAPI 02)	Randomized Phase II	Cisplatin	Seems not superior

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	Efficacy
Culine et al. 2003 (GEFCAPI 01)	Randomized Phase II	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

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 60 minutes 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

Erlotinib & Bevacizumab

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Regimen

Study	Evidence
Hainsworth et al. 2007	Phase II

Chemotherapy

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

Gemcitabine & Irinotecan

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Regimen

Study	Evidence	Comparator	Efficacy
Hainsworth et al. 2010	Phase III	PCE	Seems not superior

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	Efficacy
Greco et al. 2000	Phase II
Hainsworth et al. 2010	Phase III	Gemcitabine & Irinotecan	Seems not superior

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 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