Penile cancer

Section editor
	Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA LinkedIn

9 regimens on this page 10 variants on this page

Guidelines

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

EAU/ASCO

• 2023: Brouwer et al. European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update PubMed

ESMO

• 2013: Van Poppel et al. Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

NCCN

• NCCN Guidelines - Penile Cancer
  • 2013: Clark et al. Penile cancer: Clinical Practice Guidelines in Oncology PubMed

Neoadjuvant chemotherapy

TIP

TIP: Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence
Pagliaro et al. 2010 (MDACC ID99-194)	2000-04 to 2008-09	Phase 2

Note: cycle was repeated on day 22 if the patient's ANC was at least 1400/μL and platelet count was at least 100 x 10⁹/L. Some guidelines state that it is reasonable to give adjuvant TIP if it was not given preoperatively and pathology shows high-risk features, or to give first-line TIP in the metastatic setting; to our knowledge, there are no primary references to support this practice.

Chemotherapy

• Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1
• Ifosfamide (Ifex) 1200 mg/m² IV over 2 hours once per day on days 1 to 3
• Cisplatin (Platinol) 25 mg/m² IV over 2 hours once per day on days 1 to 3
  • Administered intravenously in 250 mL of normal saline containing 12.5 g of mannitol

Supportive therapy

• Mesna (Mesnex) 400 mg/m² IV once per day on days 1 to 3, prior to each dose of ifosfamide, then 200 mg/m² IV twice per day on days 1 to 3, at 4 and 8 hours after each dose of ifosfamide
• hydration with 3 liters of a solution of 5% dextrose, sodium chloride, potassium chloride, magnesium sulfate, and mannitol, given after cisplatin
• One of the following dexamethasone doses:
  • Dexamethasone (Decadron) 8 mg IV once 1 hour prior to paclitaxel
  • Dexamethasone (Decadron) 20 mg PO given twice, at 12 and 6 hours prior to paclitaxel
• Diphenhydramine (Benadryl) 50 mg IV once on day 1, prior to paclitaxel
• One of the following H2 blockers:
  • Cimetidine (Tagamet) 300 mg IV once on day 1, prior to paclitaxel
  • Ranitidine (Zantac) 50 mg IV once on day 1, prior to paclitaxel
  • Famotidine (Pepcid) 20 mg IV once on day 1, prior to paclitaxel
• "The use of prophylactic G-CSF was allowed but not required"

21- to 28-day cycle for 4 cycles

Subsequent treatment

• Surgery

References

1. MDACC ID99-194: Pagliaro LC, Williams DL, Daliani D, Williams MB, Osai W, Kincaid M, Wen S, Thall PF, Pettaway CA. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010 Aug 20;28(24):3851-7. Epub 2010 Jul 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00512096

VBM (Vincristine)

VBM: Vincristine, Bleomycin, Methotrexate

Regimen

Study	Dates of enrollment	Evidence
Pizzocaro et al. 1988	1979-1985	Pilot, fewer than 20 pts

Note: this is of historic interest given the toxicity of bleomycin-containing regimens.

Preceding treatment

• Surgery, within 2 to 4 weeks

Chemotherapy

• Vincristine (Oncovin) 1 mg IV once on day 1
• Bleomycin (Blenoxane) 15 mg IM once per day on days 1 & 2, given 6 hours and 24 hours after vincristine
• Methotrexate (MTX) 30 mg PO once on days 3, given 48 hours after vincristine

7-day cycle for 12 cycles

Subsequent treatment

• Surgery

References

1. Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol. 1988;27(6b):823-4. link to original article contains dosing details in manuscript PubMed
2. Review: Pagliaro LC, Crook J. Multimodality therapy in penile cancer: when and which treatments? World J Urol. 2009 Apr;27(2):221-5. Epub 2008 Aug 6. link to original article contains dosing details in manuscript link to PMC article PubMed

Adjuvant chemotherapy

DCF

DCF: Docetaxel, Cisplatin, Fluorouracil

Regimen

Study	Evidence
Necchi et al. 2011	Case report

Preceding treatment

• Surgery

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 96 hours, started on day 1 (total dose per cycle: 3000 mg/m²)

21-day cycle for 3 cycles

References

1. Case report: Necchi A, Nicolai N, Colecchia M, Catanzaro M, Torelli T, Piva L, Salvioni R. Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol. 2011 Aug 1;29(22):e650-2. Epub 2011 May 31. link to original article contains dosing details in manuscript PubMed

Metastatic or unresectable disease

BMP

BMP: Bleomycin, Methotrexate, Platinol (Cisplatin)
MPB: Methotrexate, Platinol (Cisplatin), Bleomycin

Regimen variant #1

Study	Dates of enrollment	Evidence
Haas et al. 1999 (SWOG 8520)	1986-1994	Phase 2

Note: This is likely of historic interest due to the toxicity of bleomycin-containing regimens. Bleomycin was discontinued when a total cumulative dose of 200 units/m² was reached.

Chemotherapy

• Bleomycin (Blenoxane) as follows:
  • Cycles 1 up to 10: 10 units/m² IV bolus once per day on days 1 & 8
• Methotrexate (MTX) 25 mg/m² IV bolus once per day on days 1 & 8
• Cisplatin (Platinol) 75 mg/m² IV once on day 1, given at a rate of 1 mg/min

Supportive therapy

• Normal saline IV at 250 mL/hour, starting 1 hour prior to cisplatin and continued for at least 6 hours after completion of cisplatin
• Furosemide (Lasix) 40 mg IV once on day 1, given prior to cisplatin

21-day cycles (patients who achieved CR discontinued therapy after 6 cycles)

Regimen variant #2

Study	Dates of enrollment	Evidence
Corral et al. 1998	1988-03 to 1994-01	Phase 2

Note: 21 of 29 evaluable patients in Corral et al. 1998 had penile cancer. Please see the paper for additional variations in the protocol, including some patients being treated with intraarterial therapy. This is likely of historic interest due to the toxicity of bleomycin-containing regimens.

Chemotherapy

• Bleomycin (Blenoxane) 10 mg/m² IV once per day on days 2 to 6
  • Note: Pagliaro et al. 2009 lists a "dosage of 50 mg/m² on days 2 to 6," which could be misinterpreted as 50 mg/m² for each dose, which is in contrast to the 50 mg/m² for each cycle that Corral et al. 1998 describes.
• Methotrexate (MTX) 200 mg/m² IV once per day on days 1, 15, 22
• Cisplatin (Platinol) 20 mg/m² IV over 3 hours once per day on days 2 to 6
  • Note: Corral et al. 1998 does not specify which days cisplatin is given on. Pagliaro et al. 2009 specifies that cisplatin is given on days 2 to 6. For Corral et al. 1998, the 5 day course is inferred based on the paper saying that the total dosage--presumably per cycle--was 100 mg/m².

Supportive therapy

• Leucovorin (Folinic acid) 25 mg PO every 6 hours on days 2 to 4, 16 to 18, 23 to 25, starting 24 hours after each dose of methotrexate

28-day cycles

References

1. Corral DA, Sella A, Pettaway CA, Amato RJ, Jones DM, Ellerhorst J. Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin. J Urol. 1998 Nov;160(5):1770-4. link to original article contains dosing details in manuscript PubMed
2. SWOG 8520: Haas GP, Blumenstein BA, Gagliano RG, Russell CA, Rivkin SE, Culkin DJ, Wolf M, Crawford ED. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol. 1999 Jun;161(6):1823-5. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
3. Review: Pagliaro LC, Crook J. Multimodality therapy in penile cancer: when and which treatments? World J Urol. 2009 Apr;27(2):221-5. Epub 2008 Aug 6. link to original article contains dosing details in manuscript link to PMC article PubMed

Cisplatin & Fluorouracil (CF)

Regimen

Study	Dates of enrollment	Evidence
Shammas et al. 1992	1985-1990	Pilot, fewer than 20 pts

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m²)

References

1. Shammas FV, Ous S, Fossa SD. Cisplatin and 5-fluorouracil in advanced cancer of the penis. J Urol. 1992 Mar;147(3):630-2. link to original article contains dosing details in abstract PubMed

Cisplatin & Irinotecan (IC)

Regimen

Study	Dates of enrollment	Evidence
Theodore et al. 2008 (EORTC 30992)	2004-05 to 2006-01	Phase 2

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given second
• Irinotecan (Camptosar) 60 mg/m² IV over 30 minutes once per day on days 1, 8, 15, given first

Supportive therapy

• Adequate hydration with cisplatin, per guidelines at each investigator's site
• Antiemetic medication per routine local practice.
• "Systematic premedication with atropine as of the first cycle of treatment was at the investigator's discretion but was not recommended."

28-day cycles, with up to 4 cycles before surgery in the neoadjuvant setting for T3 or N1 to N2; up to 8 cycles for patients with T4, N3, or M+ distant metastatic disease

References

1. EORTC 30992: Theodore C, Skoneczna I, Bodrogi I, Leahy M, Kerst JM, Collette L, Ven K, Marréaud S, Oliver RD; EORTC Genito-Urinary Tract Cancer Group. A phase II multicentre study of irinotecan (CPT 11) in combination with cisplatin (CDDP) in metastatic or locally advanced penile carcinoma (EORTC PROTOCOL 30992). Ann Oncol. 2008 Jul;19(7):1304-7. Epub 2008 Apr 15. link to original article contains dosing details in manuscript PubMed

Paclitaxel monotherapy

Regimen

Study	Dates of enrollment	Evidence
Di Lorenzo et al. 2011	2004-04 to 2011-01	Phase 2

Chemotherapy

• Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive therapy

• G-CSF could be used in later cycles if the patient developed febrile neutropenia during treatment
• Dexamethasone (Decadron) 8 mg PO given three times, at 12 hours before, immediately before, and 12 hours after paclitaxel

21-day cycles

References

1. Di Lorenzo G, Federico P, Buonerba C, Longo N, Cartenì G, Autorino R, Perdonà S, Ferro M, Rescigno P, D'Aniello C, Matano E, Altieri V, Palmieri G, Imbimbo C, De Placido S, Mirone V. Paclitaxel in pretreated metastatic penile cancer: final results of a phase 2 study. Eur Urol. 2011 Dec;60(6):1280-4. Epub 2011 Aug 22. link to original article contains dosing details in manuscript PubMed

Panitumumab monotherapy

Regimen

Study	Evidence
Necchi et al. 2011	Case report

Targeted therapy

• Panitumumab (Vectibix) 6 mg/kg IV once on day 1

14-day cycles

References

1. Case report: Necchi A, Nicolai N, Colecchia M, Catanzaro M, Torelli T, Piva L, Salvioni R. Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol. 2011 Aug 1;29(22):e650-2. Epub 2011 May 31. link to original article contains dosing details in manuscript PubMed

PCF

PCF: Paclitaxel, Cisplatin, Fluorouracil

Regimen

Study	Dates of enrollment	Evidence
Pizzocaro et al. 2009	2004-2006	Pilot, fewer than 20 pts

Chemotherapy

• Paclitaxel (Taxol) 120 mg/m² IV once on day 1, given first
• Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 2
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, started on day 2 (total dose per cycle: 4000 mg/m²)

Supportive therapy

• "Corticosteroids, antihistamines, and an H2 antagonist were administered before starting paclitaxel"
• "Antiemetic drugs and glutathione were administered prior to cisplatin"
• 1 liter half normal 2.5% glucose saline with 20 mEq potassium chloride and 10 mEq magnesium sulfate (MgSO4) IV given twice, before and after cisplatin

21-day cycles; "two patients received more than the standard four courses"

References

1. Pizzocaro G, Nicolai N, Milani A. Taxanes in combination with cisplatin and fluorouracil for advanced penile cancer: preliminary results. Eur Urol. 2009 Mar;55(3):546-51. Epub 2008 Jul 14. link to original article PubMed