Phase II trial of 4'-0-tetrahydropyranyladriamycin (pirarubicin) in head and neck carcinoma.

Background: 4'-0-tetrahydropyranyladriamycin (Pirarubicin, Meiji Seika (USA) Inc., New York, NY) may be less toxic than doxorubicin.
Methods: A Phase II trial of Pirarubicin was done in 26 patients who had not previously had chemotherapy and who had measurable and incurable head and neck carcinoma. All patients received an intravenous bolus dose of 60 mg/m2 Pirarubicin in the first cycle without any prophylactic antiemetic. The cycles were repeated every 3 weeks. Based on tumor response, nadir counts, or complications of myelosuppression, the doses were escalated or de-escalated by 10 mg/m2, if necessary, in the second cycle to achieve mild leukopenia (3000-4000 leukocytes/microliters).
Results: Leukopenia was mild, moderate (2000-2999 leukocytes/microliters), severe (1000-1999 leukocytes/microliters), and life threatening (less than 1000 leukocytes/microliters) in 13%, 31%, 27%, and 9% of the first two courses, respectively. The median interval to nadir leukopenia was 13 days (range, 7-21 days), with a median of 8 days (range, 5-13 days) to recover to normal. One patient with a leukocyte count of 800/microliters and an absolute granulocyte count (AGC) of 488/microliters died of sepsis 15 days after the first course. All patients had at least one course that resulted in leukopenia. One episode each of mild (100,000-150,000 platelets/microliters) and severe (25,000-49,999 platelets/microliters) thrombocytopenia occurred in the first two courses. Leukocyte, granulocyte, and platelet counts were not done routinely after the second cycle. Six patients who received four or more courses with cumulative doses of 310, 610, 340, 260, 660, and 550 mg/m2 had decrements of 0%, 1%, 7%, 10%, 12%, and 13%, respectively, in radionuclide left ventricular ejection fraction (LVEF). All other toxic effects were mild.
Conclusions: In the 24 patients with disease evaluable for response to Pirarubicin therapy, 1 had a complete response that lasted 5 months and 4 had a partial response of 2, 3, 6, and 8 months. The median survival time in patients with disease that responded to Pirarubicin therapy was 27 months; in patients with disease that did not respond to Pirarubicin therapy, the median survival time was 4 months, and in the total cohort, it was 5 months. Pirarubicin was well tolerated and was an active agent in head and neck squamous cell carcinoma.