Pirarubicin — A New Anthracycline with High Activity in Untreated Patients with Small-Cell Cancer of the Lung

Abstract

A phase II study was carried out with 16 elderly patients with small-cell cancers of the lung who had received no prior chemo- or radiotherapy. The new anthracycline, pirarubicin (formerly Theprubicin or 4′-(R)-0-tetrahydropyranyl-adriamycin-hydrochlorid), was administered at a dose of 70 mg/m² i.v. every 3 weeks. Among 16 evaluable patients (one tumor-related early death was excluded), one patient achieved a complete remission (CR), seven had a partial remission (PR), three showed initially no change, and four had disease progression. The median time from the beginning of therapy to progression was 12 months for the patient in CR and 4 months for the patients in PR (range, 2–7 months). The median survival time was 13 months for patients with CR and PR (range, 3–15+ months) and 4 months for patients with initially no change or disease progression (range, 1–8 months). The dose-limiting toxicity consisted of leukopenia; WHO grades III and IV were observed in 16% of all treatment cycles. The subjective tolerance was good; vomiting, alopecia, and stomatitis were observed in a few cases. No cardiac, hepatic, renal, or CNS toxicity was encountered. Pirarubicin is a new anthracycline, which was initially developed in Japan [1]. The structure is shown in Fig. 1. It was selected for clinical development because it showed greater or similar activity in experimental tumor models when compared with other anthracyclines [2–4]. Preclinical studies showed that pirarubicin was less cardiotoxic than adriamycin. Pirarubicin showed a different organ distribution from adriamycin, with higher concentrations found in the lungs, spleen, and thymus and lower concentrations found in the heart and gallbladder [5].