Phase II study of methotrexate, vinblastine, doxorubicin, and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck

Abstract

BACKGROUND The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population. METHODS Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4‐week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival. RESULTS Thirty‐six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33–60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1‐year progression free survival rate was 17% (95% CI, 8–36%). The median survival was 49 weeks, and the 1‐year survival rate was 43% (95% CI, 29–63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1‐year progression free survival rate was 14% (95% CI, 5–39%), and median survival was 24 weeks, and the 1‐year survival rate was 36% (95% CI, 21–63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1‐year progression free survival rate was 23% (95% CI, 9–62%), the median survival was 54 weeks, and the 1‐year survival rate was 54% (95% CI, 33–89%). CONCLUSIONS Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck. Cancer 2002;94:2224–31. © 2002 American Cancer Society. DOI 10.1002/cncr.10442

A phase II study using vinorelbine and continuous 5-fluorouracil in patients with advanced head and neck cancer

“…Although our response rates were similar to those in other studies [10,11,13,14] we had expected that the toxicity profile to be more favourable, but especially leukopenia and infections were more pronounced than expected. Leukopenia was the most common reason for reducing dose of vinorelbine.…”

Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells

“…Recent studies have evaluated the combination of GMZ with the antineoplastic vinka alkaloid vinorelbine in HNSCCs, which showed no reported pharmacokinetic or synergistic interaction 20 . Combination therapy involving anthracyclines has been analyzed recently, advocating the dosage limitations of these cardiotoxic compounds in HNSCCs 21 . However, because the results with GMZ in combination with pyridinium ceramides appear to be particularly promising, their synergistic roles in the inhibition of cell growth in HNSCC need to be evaluated in vivo using animal models and phase I clinical trials.…”