CISPLATIN, FLUOROURACIL, AND L-LEUCOVORIN INDUCTION CHEMOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK-CANCER - THE M.D.-ANDERSON-CANCER-CENTER EXPERIENCE

PURPOSE To determine the efficacy of the combination of cisplatin, flu orouracil, and high-dose 1-leucovorin (PFL) as organ-preserving induct ion therapy followed by radiotherapy in untreated patients with advanc ed squamous cell carcinoma of the head and neck. PATIENTS AND METHODS This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head an d neck, including larynx (n = 20), hypopharynx (n = 14), and oropharyn x (n = 13). The PFL regimen consisted of cisplatin 25 mg/m(2) on days 1 through 5, fluorouracil 800 mg/m(2) CI on days 2 through 6, and 1-le ucovorin 250 mg/m(2) on days 1 through 6, all by continuous intravenou s infusion every 21 to 28 days for three courses. The primary study en dpoint was initial response to and local disease control rate with PFL as induction chemotherapy, with an aim to confirm the previously repo rted complete response rate of 60% to 70%. RESULTS Of 47 patients enro lled, 46 were evaluable for response to PFL, 14 (30%) achieved a compl ete response, and 25 (54%) achieved a partial response, for an overall response rate of 84%. Of 39 patients evaluable for response after rad iation therapy, 27 (69%) achieved a complete response and 11 (28%) a p artial response. Local disease control was achieved in 37 of 46 (80%). Grade 3 or 4 toxic effects occurred frequently, with neutropenia in 2 7 (59%) of 46 evaluable patients, thrombocytopenia in 30%, mucositis i n 41%, diarrhea in 13%, and nausea/vomiting in 13%, but there were no treatment-related deaths. With a median follow-up of 35 months there h ave been nine recurrences (four local/regional and five distant) and 1 7 deaths (12 in patients with disease progression and five not directl y related to the primary tumor). Second primary tumors have developed in six patients. At 3 years 62% of the patients remain alive with no d isease progression, and the S-year survival estimate with preserved or gan function is 66%. CONCLUSION PFL induction chemotherapy produced on ly a modest complete response rate, possibly due to suboptimal dose in tensity, and was associated with substantial, although not life-threat ening, toxicity. Newer regimens and treatment modalities are still nee ded in the management of advanced squamous cell carcinoma of the head and neck.