Taxol administered as a 120 hour infusion
- 40 Downloads
A Phase I trial of Taxol administered as a 120 h infusion once every 3 weeks was conducted in 20 patients with advanced cancer. The initial dose was 5 mg/m2/d (25 mg/m2 total dose) and patients received 10 mg/m2/d, 25 mg/m2/d, 30 mg/m2/d and 36 mg/m2/d. Forty-four courses of taxol were administered and all patients were evaluable for toxicity. Grade 4 leukopenia was the dose limiting toxicity observed in 50% of patients treated with 36 mg/m2/d. Significant mucositis was also observed at 30 and 36 mg/m2/d. All toxicity resolved within three weeks of treatment and no cumulative toxicity was observed. No neurotoxicity or cardiotoxicity was observed and no episodes of hypersensitivity reaction were noted. We conclude that 30 mg/m2/d is an appropriate dose for phase II testing of this schedule.
Key wordstaxol phase I prolonged infusion
Unable to display preview. Download preview PDF.
- 1.Wani M, Taylor H, Wall M, Coggon P, McPhail A: Plant antitumor agents. VI The isolation and structure of taxol, a novel antileukemic and antitumor agent fromTaxus Brevifolia. J Am Chem Soc 93:2325–2327, 1971Google Scholar
- 2.Schiff P, Horowitz S: Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565, 1980Google Scholar
- 3.Manfredi J, Horowitz S: Taxol: an antimitotic agent with a new mechanism of action. Pharmacol Ther 25:83–125, 1984Google Scholar
- 4.Keller H, Zimmerman A: Shape changes and chemokinesis of Walker 256 carcinosarcoma cells in response to colchicine, vinblastine, nocodozole and taxol. Invasion Metastasis 6:33–43, 1986Google Scholar
- 5.Crossin K, Carney D: Microtubule stabilization by taxol inhibits initiation of DNA synthesis by thrombin and by epidermal growth factor. Cell 27:341–350, 1981Google Scholar
- 6.McGuire W, Rowinsky E, Rosenshien N, Grumbine F, Ettinger D, Armstrong D, Donehouwer R: Taxol: a novel investigational antimicrotubule agent. Ann Int Med 111: 273–279, 1989Google Scholar
- 7.Rowinsky EK, Cazenave LA, Donehower RC: Taxol: a novel investigational antimicrotubule agent. JNCI 82:1247–1259, 1990Google Scholar
- 8.Longnecker S, Donehower R, Cates A, Chen T, Brundrett R, Grochow L, Ettinger D, Colvin M: High-performance liquid chromatography for taxol in human plasma and urine and pharmacokinetics in a phase I trial. Cancer Treat Rep 71:53–59, 1987Google Scholar
- 9.Rowinsky EK, McGuire WP, Guarnieri T, Fisherman J, Christian M, Donehower R: Cardiac disturbances during administration of Taxol. J Clin Oncol 9:1704–1712, 1991Google Scholar
- 10.Weiss R, Donehower R, Weirnik P, Ohnuma T, Gralla R, Trump D, Baker J, Van Echo D, Leyland-Jones B: Hypersensitivity reactions from Taxol. J Clin Oncol 8:1263–1268, 1990Google Scholar