151. Phase I/II study of amrubicin, a novel 9-aminoanthracycline, in patients with advanced non-small-cell lung cancer.
- Author
-
Sugiura T, Ariyoshi Y, Negoro S, Nakamura S, Ikegami H, Takada M, Yana T, and Fukuoka M
- Subjects
- Adult, Aged, Anthracyclines adverse effects, Antineoplastic Agents adverse effects, Electrocardiography drug effects, Female, Humans, Injections, Intravenous, Leukopenia chemically induced, Male, Maximum Tolerated Dose, Middle Aged, Neutropenia chemically induced, Survival Analysis, Topoisomerase II Inhibitors, Anthracyclines therapeutic use, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Purpose: Amrubicin is a novel, totally synthetic 9-aminoanthracycline. The present phase I/II study was performed to define its maximum-tolerated dose (MTD), efficacy and toxicity in the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Chemonaive patients were required to have cytologically or histologically proven measurable NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and adequate organ functions. Amrubicin was administered by daily intravenous injection for 3 consecutive days every 3 weeks., Results: In a phase I study, four patients were enrolled at dose level 1 (40 mg/m(2)/day) and four at dose level 2 (45 mg/m(2)/day). No dose limiting toxicity (DLT), which was defined as toxicity consisting of grade 4 neutropenia and leukopenia lasting four days or more, and grade 3 or 4 toxicity other than neutropenia, leukopenia, anorexia, nausea/vomiting, and alopecia, was observed at these dose levels. Subsequently, at dose level 3 (50 mg/m(2)/day), 3 of 5 patients experienced DLTs (leukopenia, neutropenia, thrombocytopenia, or gastrointestinal complications). The MTD and recommended dose (RD) were determined to be 50 mg/m(2)/day and 45 mg/m(2)/day, respectively. Three partial responses (PRs) were achieved in 13 patients (response rate, 23.1%) in a phase I study. In a phase II study, 15 patients were assessable for efficacy and toxicity at the RD, and four PRs were obtained (response rate, 26.7%). The major toxicities were leukopenia and neutropenia, while non-hematologic toxicities were mild. The overall response rate in the combined patient population of the phase I/II study was 25.0% (7 PRs in 28 patients), with a 95% confidence interval of 10.7% to 44.9%., Conclusion: Amrubicin exerted promising antitumor activity on NSCLC with acceptable toxicity.
- Published
- 2005
- Full Text
- View/download PDF