DX-8951f, a Hexacyclic Camptothecin Analog, on a Daily-Times-Five Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies

Abstract

The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m(2)/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule.

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

“…155–158 In patients with advanced solid malignancies on a schedule of 30 min i.v. infusions five days a week every three weeks, MTDs of 0.3 and 0.5 mg/m 2 (~0.008 and 0.013 mg/kg) were recommended for heavily pretreated patients and mildly pretreated patients, respectively.…”

“…infusions five days a week every three weeks, MTDs of 0.3 and 0.5 mg/m 2 (~0.008 and 0.013 mg/kg) were recommended for heavily pretreated patients and mildly pretreated patients, respectively. 155 An average half-life of 8.75 h was determined, with severe myelosuppression experienced at doses above the MTD. Patients with advanced leukemia, however, were treated for 30 min on five consecutive days for three weeks through i.v.…”

Quantitative acid hydrolysis of DE-310, a macromolecular carrier system for the camptothecin analog DX-8951f

“…Recently, a novel camptothecin analog, DX-8951f, has improved water solubility and exhibits antitumor activity against both murine tumors and human tumor xenografts in mice [11][12][13]. High efficiency of DX-8951f in clinical tests is expected, although toxicity is a concern as with other camptothecin analogs [14].…”

DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors

“…Several phase I studies in various solid tumor types and hematological malignancies have proven the low toxicity of DX-8951 in a variety of treatment schedules [32][33][34][35]. Reversible myelosuppression was the dose-limiting toxicity in most patients [36,37].…”