Neoadjuvant Chemotherapy

Interestingly, durable complete remissions can be obtained in patients with primary resectable and nonresectable locally advanced nodal and soft tissue disease by neoadjuvant chemotherapy followed by surgical removal of residual disease.9 10 In a review on advanced penile carcinoma, Culkin and Beer combined the results of all available studies on cisplatin-based induction chemotherapy. 1 1 Clinical responses were found in 24 of 35 patients (69%) and 15 of the responding patients (43%) underwent subsequent surgery. Eight patients (23%) were alive without evidence of disease after 1-10 years of follow-up.

In our own institution over a 33-year period, a total of 20 patients were treated with induction chemotherapy in an attempt to downstage primary unresectable inguinal lymphadenopathy. Five different chemotherapy regimens were used. An objective tumor response was achieved in 12 of 19 evaluable patients. The overall 5 year survival was 32%, while there was a significant difference (p = 0.012) in survival between responders (5-year survival 56%) and nonresponders (all nonresponders died within 9 months). Nine responders underwent subsequent surgery with curative intent, eight of them were long-term survivors without evidence of recurrent disease. The toxicity of the induction therapy was relatively high with three toxic deaths and discontinuation of treatment in one patient. All four patients were treated with bleomycin/methotrexate, combined with cisplatin in 3 and with vincristine in 1. Therefore, we do not consider combined treatment with bleomycin and methotrexate as the preferred treatment for penile cancer, either as induction therapy or as palliative therapy.7 Our group participated in the EORTC 30992 study in which cisplatin in combination with irinotecan was studied in metastatic or locally advanced penile carcinoma. 1 2 In this series three patients treated in the neoadjuvant setting had a pathological complete remission. In our clinic we carefully select patients for induction chemotherapy in a multidisciplinary setting.

Addition of the taxane docetaxel to cisplatin and 5-FU showed improved progression-free and overall survival in patients with unresectable squamous cell carcinoma of the head and neck compared with the standard regimen of cisplatin and 5-FU.13 Also penile cancer taxane-based chemotherapy seems to be both active and safe and has recently shown promising results.10,14 We are currently studying the cis-platin-5FU-docetaxel regimen as induction therapy in a phase II study.

Treatment of head and neck squamous cell carcinoma with the epidermal growth factor receptor (EGFR) targeting antibody cetuximab has shown prolonged survival in this patient population. 15 Interestingly, since EGFR is overexpressed in penile cancer, implementation of cetuximab in combination with cisplatin-based chemotherapy for the treatment of this disease might be of interest. Studies evaluating the effect of cetuximab-containing regimens in the treatment of penile cancer have been initiated.

Evaluating the tumor response to induction therapy by CT scanning alone was insufficient to identify good prognosis responders and separate these patients from poor prognosis nonresponders, prior to surgical resection of residual disease. An interesting new approach is to add 18FDG-PET to CT scanning for monitoring tumor response.16,17 In our clinic preliminary results show that molecular-based imaging may be potentially more reliable compared to response assessment using CT scanning alone. In this way, early response to chemotherapy (after two cycles) can be reliably assessed.

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