No survival difference between cisplatin and 5-fluorouracil or cisplatin and paclitaxel

A phase III trial from the Eastern Cooperative Oncology Group finds no difference in outcomes between standard infusional cisplatin and 5-flurouracil (CF) and cisplatin and paclitaxel (CP).It is difficult to treat recurrent or metastatic squamous cell carcinoma of the head and neck because of the characteristics of the tumours and the usually poor health status of the patients. Phase II trials have shown paclitaxel combinations are safe and effective.This randomised phase III trial included patients with measurable or assessable squamous cell carcinoma of the head and neck that was not curable by surgery or radiation therapy. Patients were randomised to standard cisplatin and 5-fluorouracil (CF) by continuous intravenous infusion for four days or to cisplatin and paclitaxel (CP) for three hours on day one every three weeks. The primary endpoint was overall survival at one year. Patients that developed grade 2 or more neuropathy or renal impairment were changed to carboplatin. There were 109 patients in each group and 204 were included in the intention to treat analysis. Most patients had performance status of 1 and 60.6% in the CF group and 52% in the CP group had metastatic disease. There were seven deaths in the CF group and five in the CP group. Haematological adverse events and diarrhoea were more common in the CF group but there was no significant difference between groups in grade 3 or higher toxicity. As a further indication of toxicity, 21 patients in the CF group and seven in the CP group switched to carboplatin.There were no major differences in the endpoints. One year overall survival was 41.4% in the CF group and 32.4% in the CP group (p=0.49) and estimated median survival was 8.7 months and 8.1 months respectively. There was no difference in response rates between groups and performance status was the only predictor for survival.The authors suggested that the higher response rates seen in earlier studies may be due to a higher proportion of patients with assessable disease and less reliance on imaging in the previous studies which may have overestimated the response.The authors noted that quality of life and pain intensity measures may differ because of the methods of administration and that these will be reported separately. The authors concluded that survival in this population remains poor and that biologically targeted agents including cetuximab, gefitinib and erlotinib may be more effective.Reference...