Current developments in antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids

The antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids represent a major portion of the therapeutic armamentarium against almost all treatable neoplasms. However, their use has been limited by the acquisition of drug resistance as well as by serious nonhematologic toxicities such as cardiac toxicities with the anthracyclines, pulmonary toxicities with bleomycin, and peripheral nervous system toxicities with the vinca alkaloids. This paper discusses several new developments over the last year, particularly advances in our understanding of 1) the antitumor efficacy and ultimate clinical role of several novel analogues that appear to have improved therapeutic indices in certain malignancies such as idarubicin in acute myelogenous leukemia, epirubicin in breast cancer, and vinorelbine in breast and non-small cell lung cancers; 2) the nature, risks, detection, and prevention of serious nonhematologic toxicities such as the role of the carbon monoxide diffusion capacity test in the early detection of pulmonary toxicity from bleomycin, and youth as a risk factor for anthracycline cardiomyopathy; 3) the optimal scheduling and administration of these agents including chronic low-dose oral, infusional, and intraperitoneal administration schedules for the epipodophyllotoxins and infusional schedules for the vinca alkaloids; 4) differences in the pharmacology and recommendations for the use of the epipodophyllotoxin etoposide in patients with excretory organ dysfunction; and 5) the clinical feasibility of reversing multidrug resistance by using calcium channel blockers, the potential utility of other classes of agents to modulate multidrug resistance in the clinic, and new insights on resistance to bleomycin.