Background: In 1982, the Illinois Cancer Center initiated a Phase II trial in which the following treatment was administered: Induction chemotherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administered before definitive local therapy. Definitive local therapy, consisting of surgery, radiation, or both, was followed by three cycles of the same chemotherapy program.
Methods: Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant metastases. Three cycles of induction chemotherapy were given. Cisplatin, 100 mg/m2, was infused over 60 minutes on Day 1; thereafter, 5-FU (1000 mg/m2/day) was given continuously for 5 days. Cycles were repeated at 3-week intervals. Local therapy was individualized, according to tumor stage and site. Patients who responded were to receive an additional three cycles of chemotherapy after surgery or radiation.
Results: Eighty-one patients were entered into the trial, and 71 were considered both eligible and evaluable. After induction chemotherapy, 59 patients (83%) responded, 23 of whom experienced complete response. Sixty-nine patients completed definitive local treatment, but only 22 proceeded to the planned adjuvant cycles of treatment. Median follow-up of surviving patients was 12 years. At last follow-up, 13 patients were alive 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 themselves. Overall, nine patients had second primary malignancies. Thirty-four 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 resulted from second primary cancers. Four patients died of unrelated causes, and two suffered lethal acute toxicity from the chemotherapy program. Late toxicity was moderate. Among 23 patients surviving at least 6 years, there were 3 cases of hypothyroidism, presumed to be secondary to radiation. Xerostomia was modest, consistent with usual radiation effects. Of the 13 patients who were alive and free of malignancy at last follow-up, none had clinical manifestations of serious late end organ toxicity.
Conclusions: During long term follow-up after multimodal treatment of locally advanced squamous cell carcinoma, no obvious benefit was observed from the chemotherapy component of the treatment regimens rendered. Only 21% of patients achieved 10-year survival with the following causes of failure, in descending order of frequency: disease recurrence, second malignancies, other medical problems, and treatment-related deaths. The results of this trial are consistent with the results of other induction chemotherapy trials, indicating the need for innovative treatment strategies. These data do not support the continued use of induction chemotherapy with the cisplatin and infusional 5-FU program.