Phase II trial of mitoxantrone in head and neck carcinoma

Nineteen patients with measurable and incurable head and neck carcinoma (17 squamous cell and two adenoid cystic) received intravenous bolus doses of 14 mg/m² mitoxantrone in the first course. The doses were escalated or de-escalated by 2 mg/m² in subsequent courses, based on leukocyte nadir, to achieve mild (3,000-3,999/mm³) or moderate (2,000-2,999/mm³) toxicity and response. The courses were repeated every 3 weeks. All 60 courses were evaluated for toxicity. Leukopenia was mild, moderate, severe (1,000-1,999/mm³), and life-threatening (<1,000/mm³) in 17%, 23%, 42%, and 2% of courses, respectively. Mild thrombocytopenia (100,000-129,999/mm³) occurred in two courses. The median interval to nadir leukopenia was 14 days (range 7-36) with a median of 13 days (range 3-50) to recover to normal. After the first course, leukopenia was mild in 16%, moderate in 32%, severe in 26%, and life-threatening in 5%. One patient died of pulmonary embolism 8 days after the first course and had concomitant leukocyte count of 700/mm³. Eighteen patients had at least one course resulting in leukopenia. Three of six patients receiving ≥4 courses (cumulative dose 56-102 mg/m²) had an asymptomatic decrement of 14%, 17%, and 29%, respectively, in radionuclide left ventricular ejection fraction. The other toxicities were mild. In the 16 patients with squamous cell carcinoma that could be evaluated for response, one had a partial response lasting 8 months, and six had stable disease. One of the two patients with parotid adenoid cystic carcinoma had a minor response lasting 16 months. Mitoxantrone on a bolus schedule has minimal activity and is not indicated in head and neck squamous cell carcinoma.