High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study.

Abstract:

:A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was cardiac toxicity. Objective tumor regression occurred in 14 of 18 evaluable cases, with a median duration of 3.5 months. Pharmacokinetic evaluation of melphalan in 20 patients revealed a dose-related increase in maximum plasma concentration (Cmax) and area under the curve (AUC). Perturbation of the melphalan plasma half-life and AUC, associated with severe toxicity, resulted when renal insufficiency occurred. The results suggest that high-dose combination cyclophosphamide, cisplatin, and melphalan produces frequent, rapid responses in breast cancer, melanoma, and sarcoma, although with significant extramedullary toxicity. The pharmacokinetics suggest that modification of the treatment schedule may result in a reduction of treatment-related toxicity.

authors

Peters WP,Stuart A,Klotman M,Gilbert C,Jones RB,Shpall EJ,Gockerman J,Bast RC Jr,Moore JO

doi

10.1007/BF00435840

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

377-83

issue

6

eissn

0344-5704

issn

1432-0843

journal_volume

23

pub_type

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