Neoadjuvant therapy for organ preservation in head and neck cancer

Objectives/Hypothesis: We designed two sequential trials of induction chemo therapy followed by definitive radiation in patients with potentially resec table head and neck cancer to determine whether organ preservation is feasi ble without apparent compromise of survival. Study Design: Both trials were Phase II studies. Methods: Two clinical trials were conducted sequentially at the University of Michigan, Fifty-two patients enrolled in the first st udy and were treated with a planned three cycles of carboplatin and 5-fluor ouracil, Patients who achieved at least 50% reduction in the size of the pr imary tumor received definitive radiation therapy, to a dose of 6600 to 138 0 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the c hemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin, Resp onders were treated with accelerated radiation therapy to a total dose of 7 120 cGy delivered in 41 fractions over 5.5 weeks. Results: Toxicity and res ponse were similar in both trials; therefore, the results are reported firs t separately and then combined for all 89 patients. Tumor sites included: o ropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of p atients tolerated all three cycles of chemotherapy and toxicity was mild. R esponse to chemotherapy was: 48% complete response at the primary tumor sit e, and 34% partial response at the primary tumor site. initial organ preser vation at individual tumor sites was: oropharynx, 58% hypopharynx, 59%. Med ian survival was 28 months, and Survival at 3 and 5 years was 40% and 24%, respectively, Conclusions: These two regimens were well tolerated, and surv ival did not appear to be compromised by organ preservation treatment compa red with historical controls, This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debi litating.