Neoadjuvant Paclitaxel, Ifosfamide, and Cisplatin Chemotherapy for Metastatic Penile Cancer: A Phase II Study

Men with penile squamous cell carcinoma and regional lymph node involvement have a low probability of survival with lymphadenectomy alone. A multimodal approach to treatment is desirable for such patients. We performed a phase II study of neoadjuvant chemotherapy with the objective of determining the response rate, time to progression (TTP), and overall survival (OS) among patients with bulky adenopathy.Eligible patients had stage N2 or N3 (stage III or stage IV) penile cancer without distant metastases. Neoadjuvant treatment (four courses every 3-4 weeks) consisted of paclitaxel 175 mg/m(2) administered over 3 hours on day 1; ifosfamide 1,200 mg/m(2) on days 1 to 3; and cisplatin 25 mg/m(2) on days 1 to 3. Clinical and pathologic responses were assessed, and patient groups were compared for TTP and OS.Thirty men received chemotherapy of whom 15 (50.0%) had an objective response and 22 (73.3%) subsequently underwent surgery. Three patients had no remaining tumor on histopathology. Nine patients (30.0%) remained alive and free of recurrence (median follow-up, 34 months; range, 14-59 months), and two patients died of other causes without recurrence. Improved TTP and OS were significantly associated with a response to chemotherapy (P < .001 and P = .001, respectively), absence of bilateral residual tumor (P = .002 and P = .017, respectively), and absence of extranodal extension (P = .001 and P = .004, respectively) or skin involvement (P = .009 and P = .012, respectively).The neoadjuvant regimen of paclitaxel, ifosfamide, and cisplatin induced clinically meaningful responses in patients with bulky regional lymph node metastases from penile cancer.