5-Fluorouracil/folinic acid/cisplatin-combination and simultaneous accelerated split-course radiotherapy in advanced...

In advanced inoperable head and neck cancer radiotherapy alone is unsatisfying. Better results can be obtained by simultaneous 5-Fluorouracil/Cisplatin-chemotherapy and irradiation. The cytotoxicity of 5-Fluorouracil can be enhanced synergistically by adding Folinic Acid in excess. In a clinical phase II trial 62 previously untreated patients suffering from unresectable AJCC-stage III (4 pts.) and IV (58 pts.) squamous cell carcinoma of the head and neck were treated with a simultaneous chemoradiotherapy consisting of high-dose Folinic Acid in addition to a 5-Fluorouracil/Cisplatin combination and of accelerated split-course radiotherapy. As results, three pts. died from tumor arrosion bleeding during the treatment. Median follow up time of the surviving pts. is 27 + months (range 18-44 months). 48/62 pts. (77%) achieved complete remission, 11/62 pts. (18%) partial remission. Presently, 32 pts. (52%) are without evidence of disease. Actuarial three years overall survival rate (Kaplan-Meier method) out of 62 pts. in 53%. Actuarial disease free survival and local tumor control rates at three years are 58% and 72%. Mucositis was severe but tolerable, bone marrow depression was moderate to marked. In conclusion, this combined simultaneous modality approach is highly effective in locally advanced head and neck cancer. It seems to provide superior survival and local control rates as compared to conventional radiotherapy or sequential chemo-radiotherapy or as compared to simultaneous 5-Fluorouracil/Cisplatin and non-fractionated radiotherapy. A comparative phase III study is required.