Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001)

Abstract

Background:Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease.Methods:Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m−2 day 1, cisplatin 60 mg m−2 day 1, 5-flurouracil 750 mg m−2 per day days 1–5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A'Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival.Results:10/26 evaluable patients (38.5%, 95% CI: 20.2–59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event.Conclusion:Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.

Identification of somatic gene mutations in penile squamous cell carcinoma

“…Active agents include 5‐fluoracil, bleomycin, methotrexate, and cisplatin, used either as single agents or in various combinations. Few randomized trials have compared the benefit of combination over single agent therapy, and although some combinations seem more effective than single agents, toxicity may be substantial (Di Lorenzo et al, ; Carthon et al, ; Nicholson et al, ). Objective response rates range from 20 to 70%, but are usually short lived (4‐6 months) (Shammas et al, ; Haas et al, ).…”

Role of chemotherapy in treatment of squamous cell carcinoma of the penis

“…Some of these are changing; for example, investigators in the United Kingdom were able to enroll 29 patients on a prospective phase II study in just 15 months. 6 This was facilitated by the designation of 9 regional specialty centers for the treatment of all patients with penile cancer in that country. It is now feasible to conduct a large randomized trial such as the proposed InPACT trial.…”

“…Despite preliminary data suggesting that addition of docetaxel to 5-FU and cisplatin was uniquely effective, 11 the response rate in a completed prospective study of TPF was only 38.5%, with grade 3 or grade 4 toxicities experienced by 65.5% of the patients. 6 Based on these data, TPF has not been recommended for routine use.…”

“…TPF is not recommended for palliative treatment in stage IV disease, despite having a slightly higher response rate in the phase II experience, because it also had a higher rate (65.5%) of grade 3 and 4 toxicity. 6 This raises the question of whether TIP should be recommended for palliative treatment of patients with distant metastases. There are no published data on the efficacy of TIP for treatment of patients with visceral involvement or distant metastases.…”

Complete Remission of Locally Advanced Penile Squamous Cell Carcinoma after Multimodality Treatment

“…13,15 A phase II clinical trial using docetaxel (XT), CDDP and fluorouracil (5-FU) reported a response rate of 38.5%, but 65.5% of patients in this study experienced severe or life-threatening toxicities. 16 In the phase II clinical trial by Pagliaro et al , 4 cycles of TIP in patients with N2 or N3 disease without distant metastasis produced clinically significant responses in 50% of patients with 53% experiencing grade 3 or 4 adverse events. 9 The patient in our first case tolerated TIP well and achieved CR with pathology showing only granulomatous tissue post-chemotherapy.…”