Purpose: We conducted this study to evaluate the efficacy and toxicity of fractionated high-dose cisplatin as neoadjuvant organ-preserving chemotherapy, followed by definitive radiotherapy, for untreated and advanced squamous cell carcinoma of the larynx.
Materials and methods: From August 1990 to April 1994, 32 patients bearing previously untreated advanced squamous cell carcinoma of the larynx (12 stage III and 20 stage IV) received three courses of high-dose cisplatin (100 mg/m2 on day 1 and day 8 every 28 days) before definitive external radiation therapy with 65 to 70 Gy (180-200 cGy daily for 6-8 weeks). Twenty-eight patients were men; median age was 57 years (range, 31-69); and median performance status (ECOG) was 1 (0-2).
Results: With an average follow-up time of 18 months (range, 6-47), 30 patients are evaluable for response and 32 for toxicity. Responses after three courses of chemotherapy were: complete response, 18 patients (60%), and partial response, 7 patients (23%), for an overall response rate of 83%. Only one patient showed progressive disease. Fifteen patients (50%; 12 complete and 3 partial responders) had pathologic complete remission. Eighty percent of patients had no evidence of disease after the therapeutic program. Median disease-free survival was 24 months, and median overall survival was 28 months (range, 6-47). Overall, in 46% of all evaluable patients, organ preservation with acceptable function was achieved. Disease-free survival and larynx preservation were strongly correlated with pathologic complete remission. The average dose intensity received at the end of the third course of therapy was 47 mg/m2/week. There were no drug-related deaths. The main acute toxicity was grade 2-3 nausea and vomiting in 75% of patients. Two patients developed renal impairment after the first course of cisplatin. Ototoxicity (grade 2-3) was seen in 43% of patients, and peripheral neuropathy (grade 2-3) was observed in 12% of patients. In contrast, myelotoxicity and mucositis were mild.
Conclusion: In conclusion, this strategy with fractionated high-dose cisplatin given on an outpatient basis is an attractive approach that produces a high rate of complete response and larynx preservation with an advantageous toxicity profile.