PHASE-II STUDY OF INDUCTION AND ADJUVANT CHEMOTHERAPY FOR SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - A LONG-TERM ANALYSIS FOR THE ILLINOIS-CANCER-CENTER

BACKGROUND, In 1982, the Illinois Cancer Center initiated a Phase II t rial in which the following treatment was administered: Induction chem otherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administ ered before definitive local therapy Definitive local therapy, consist ing of surgery, radiation, or both, was followed bg three cycles of ti le same chemotherapy program. METHODS. Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant me tastases. Three cycles of induction chemotherapy were given. Cisplatin , 100 mg/m(2) as infused over 60 minutes on Day 1; thereafter, 5-FU (1 000 mg/m(2)/day) was given continuously for 5 days. Cycles were repeat ed at 3-week intervals. Local therapy was individualized according to turner stage and site. Patients who responded were to receive an addit ional three cycles of chemotherapy after surgery or radiation. RESULTS . Eighty-one patients were entered into tile trial, and ?1 were consid ered both eligible and evaluable. After induction chemotherapy, 59 pat ients (83%) responded, 23 of whom experienced complete response, Sixty -nine patients completed definitive local treatment, but only 22 proce eded to the planned adjuvant cycles of treatment. Median follow-up of surviving patients was 12 years At last follow-up, 13 patients were al ive and free of malignancy, 9 of whom never had disease recurrence or a second primary tumor. These 13 patients had an acceptable quality of life, were ambulating, and were fully capable of caring for themselve s. Overall, nine patients had second primary malignancies . Thirty-fou r percent of patients were alive at 5 years, and 21% were alive at 10 years. Of 58 deaths, 44 resulted from progressive disease and 8 result ed from second primary cancers. Four patients died of unrelated causes , and two suffered lethal acute toxicity from tile chemotherapy progra m Late toxicity was moderate. Among 23 patients surviving at least 6 y ears, there were 3 cases of hypothyroidism, presumed to be secondary t o radiation. Xerostomia was modest, consistent with usual radiation ef fects. Of the 13 patients who were alive and free of malignancy at las t follow-up, none had clinical manifestations of serious late end orga n toxicity. CONCLUSIONS. During long term follow-up after multimodal t reatment of locally advanced squamous cell carcinoma, no obvious benef it was observed from the chemotherapy component of the treatment regim ens rendered. Only 21% of patients achieved 10-year survival with the following causes of failure, in descending order of frequency : diseas e recurrence, second malignancies, other medical problems, and treatme nt-related deaths. The results of this trial are consistent with the r esults of other induction chemotherapy trials, indicating the need for innovative treatment strategies. These data do not support the contin ued use of induction chemotherapy with the cisplatin and infusional 5- FU program. (C) 1997 American Cancer Society.