Neoadjuvant therapy for organ preservation in head and neck cancer.

OBJECTIVES/HYPOTHESIS: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible 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 study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. RESULTS: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. CONCLUSIONS: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

Intensive induction chemotherapy and radiation for organ preservation in patients with advanced resectable head and neck carcinoma.

PURPOSE: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the head and neck. The regimen consisted of intensive chemotherapy followed by radiation therapy alone for patients with good response to treatment. The end points of the study were response rate, organ preservation, toxicity, and survival. PATIENTS AND METHODS: Forty-two eligible patients with carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses were enrolled. Induction chemotherapy consisted of three cycles of mitoguazone, fluorouracil (5-FU), and high-dose continuous infusion cisplatin. Patients who had a complete response to chemotherapy, or whose tumor was downstaged to T1N1, were treated with definitive radiation therapy, to a total dose of 66 to 73.8 Gy. Patients with residual disease greater than T1N1 underwent surgery and postoperative radiation. RESULTS: The overall response rate to chemotherapy was 84%, with a 43% complete response rate, and a 68% complete response rate at the primary tumor site. Sixty-nine percent of patients (29 of 42) were initially spared surgery to the primary tumor site, and four of these patients (14%) required neck dissection only, after radiation therapy. These tumor sites included oral cavity, oropharynx, hypopharynx, larynx, and sinuses. Eventually, five of these patients (17%) required salvage surgery and eight patients (28%) had unresectable or metastatic relapses. With a median follow-up duration of 38.5 months, 36% of all patients have had preservation of the primary tumor site and remain disease-free. The median survival duration is 26.8 months. Toxicity was substantial, with a 70% incidence of grade 3 to 4 granulocytopenia and two septic deaths. CONCLUSION: Organ preservation without apparent compromise of survival was achieved in patients with selected nonlaryngeal sites of head and neck carcinoma. Larger site-specific trials with less toxic regimens conducted in randomized fashion are required to extend these data.