A randomized trial between two neoadjuvant chemotherapy protocols: CDDP + 5-FU versus CDDP + VP16 in advanced cancer of the head and neck.

We investigated a phase III randomized trial to compare efficacy and tolerance of CDDP + 5-FU to CDDP + VP16, both given intravenously in patients with unresectable advanced head and neck cancer. The 197 eligible patients were paired off successively on the basis of tumor sites and UICC stage. Comparisons were made through sequential closed plans. In 179 patients, tumor beds and cervical lymph nodes were irradiated, and 20 patients underwent salvage surgical procedures. Cisplatin plus 5-fluorouracil showed a response (CR + PR) rate of 15% greater than that observed with cisplatin plus etoposide (alpha=0.05, power 70%). Complete responses played a major role in the CDDP + 5-FU regimen. Furthermore, we noted a higher cervical node regression with this chemotherapy combination. Because radiotherapy was administered after chemotherapy, we could not analyze the mean duration response for each protocol. No significant difference in survival existed between the two groups. Myelosuppression was the most frequent sign of toxicity observed, especially with the CDDP + VP16 regimen. Mucositis was rare with allopurinol protection. In the CDDP + 5-FU group, one patient had grade 4 cardiac dysfunction, and 3 patients exhibited unconsciousness that may be related to cerebral vascular damage. Thirteen patients died, with 8 cases related to septic shock (5 CPPP + VP16 and 3 CDDP + 5-FU). Cisplatin plus 5-FU chemotherapy showed a satisfactory efficacy and acceptable toxicity profile compared with CDDP + VP16, with caution to patients with a cardiac or vascular history. Although we could not show a benefit in survival with the CDDP + 5-FU protocol, this trial supports literature data and confirms that this regimen may be proposed as a first-line therapy in advanced cancer of the head and neck.

New approach to pre-therapeutic prognosis in advanced squamous cell carcinoma of the head and neck.

The Bleomycin (BLM)-induced apoptosis in peripheral blood mononuclear cells (PBMC), from patients with advanced squamous cell carcinoma of the head and neck (SCCHN), cultured in vitro with PHA, was tested as a predictive indicator of the survival time. The rates of the PBMC BLM-induced apoptosis and of the cycling-PBMCs, measured respectively after Giemsa- and Feulgen-staining were determined in 25 patients before induction chemotherapy. By using the Cox model, the survival probability was significantly and independently increased for a high percentage of PBMC BLM-induced apoptosis and a high rate of cycling PBMCs. (Chi-2(2): 10; p=0.007). Six patients, in whom both PBMC variables were simultaneouly greater than the median values, showed a median survival time as long as 60 months versus 10 months for the other 19. Conclusively, the PBMC susceptibility to BLM-induced apoptosis as well as the PBMC capability for cycling may be regarded as independent pretherapeutic prognosis factors for patients with advanced SCCHN.