Chemotherapy prior to local therapy in advanced squamous cell carcinoma of the head and neck. <i>Preliminary assessment of an intensive drug regimen</i>

Abstract

33 patients with locally and regionally advanced squamous cell carcinoma of the head and neck were treated with a single course of a combination of chemotherapy. Twenty-two of these patients were previously untreated, while the other eleven were previously treated with radiation therapy and/or surgery. Seventeen of the previously untreated patients had stage IV (M0) and the other 5 had stage III disease. Of the 33 patients; 26 received a three drug combination that consisted of: Cis-diamminedichloro-platinum II (DDP), Bleomycin (Bleo) and high dose Methotrexate (MTX) and leucovorin rescue. DDP was given on day 1; 100 mg/m2 with hydration and Lasix and Mannitol diuresis over 6 hours intravenously (iv). Bleo was administered as 15 units/m2 iv push on day 5 followed by 15 units/m2 a day for 5 days by continuous iv infusion. On day 10, the patient was evaluated and if there was no evidence of any toxicity, the patient was hydrated and alkalinated and MTX was given as 50 mg/m2 by rapid iv infusion followed by 1500 mg/m2 over 36 hours while maintaining the hydration and alkalinization. This was followed immediately by leucovorin; 25 mg/m2 iv over 15 minutes, then 200 mg/m2 over 12 hours iv. The patient then received leucovorin 25 mg/m2 intramuscularly (im) every 6 hours for 6 doses. The other 7 patients tolerated the first two drugs only, i.e., DDP and Bleo, and received no MTX because of decreased creatinine clearance. All patients were evaluated for response 2 weeks after the chemotherapy course, and prior to the local-regional therapy that consisted of surgery or radiotherapy. The response rates were 72.7% in previously untreated patients (16/22); with 4 complete responses (CR) and 12 partial responses (PR), and 54.5% in the previously treated group (6/11) all of them were PR. However, if we excluded three unevaluable patients that were considered failures from the study, the response rate in previously untreated patients would be 16/19 or 84.2%. The duration of response to such single course of chemotherapy was estimated to be 8–12 weeks. The toxicity in the 33 patients included vomiting in 18, alopecia, in 33, WBC below 2000 in 6, platelet count less than 50,000 in 6, mucositis in 7, and peak serum creatinine above 2 in 4 patients with two deaths. This combination chemotherapy seemed to be very effective in squamous cell carcinoma of the head and neck and could be applied prior to local-regional therapy. However, such program is still in experimental stages and should be carried out only in centers that have adequate facilities for close monitoring of the patients. Cancer 43:1025-1031, 1979.