Phase II study of high-dose aclarubicin in previously treated patients with small-cell lung cancer
Aclarubicin is one of the antitumor anthracyclines (aclacinomycin A) isolated from Streptomyces galilaeus by Oki et al. in 1975 [9]. Preclinical evaluation of aclarubicin has revealed several important differences in the drug's properties relative to the classic anthracyclines doxorubicin and daunombicin. Cellular uptake of aclarubicin occurs more rapidly [11], and in contrast to the classic anthracyclines, aclarubicin does not stimulate topoisomerase II-mediated DNA breaks [6]. Furthermore, only limited, if any crossresistance with aclarubicin has been demonstrated in the two well-defined doxorubicin-resistant phenotypes, P-gp MDR (P-glycoprotein multidrug-resistant) and at-MDR (altered topoisomerase MDR) cells [4, 5]. Aclarubicin given on a single-bolus schedule has not shown clinically relevant activity against solid tumors [1, 2, 7]. In contrast, the drug has demonstrated activity against leukemia. However, these trials have involved the administration of aclarubicin on prolonged schedules over 3 5 consecutive days and at higher cumulative doses [3, 8, 10, 12]. The present report describes a phase II trial of high-dose aclarubicin given on a 3-day treatment schedule to previously treated patients with small-cell lung cancer.