A phase I trial of ifosfamide, mesna, and cisplatin in advanced non‐small cell lung cancer a cancer and leukemia group B study


Journal Article

Background. This Phase I study was designed to determine the maximum tolerated dose of ifosfamidemesna with a fixed dose of cisplatin without growth factor or hematopoietic precursor support. Methods. Twenty‐five patients with previously untreated advanced non‐small cell lung cancer were treated at four dose levels. Initially, the cisplatin dose was 100 mg/m2 given on day 1. Seven patients were treated with ifosfamide 2.0 g/m2 days 1 to 3, and six patients received ifosfamide 2.5 g/m2 days 1 to 3. Mesna was given at 20% of the ifosfamide dose at 0, 4, and 6 hours after ifosfamide. Cycles were repeated every 4 weeks. Results. Dose‐limiting toxicities (myelosuppression and renal toxicity) were seen at dose level 2 (ifosfamide 2.5 g/m2). Because 5 of the first 13 patients experienced Grade 3 renal toxicity, the study was amended to give cisplatin in divided doses. An additional six patients each were treated at dose level 3 (ifosfamide 2.0 g/m2 days 1–3) and dose level 4 (ifosfamide 2.5 g/m2 days 1–3) with cisplatin 33 mg/m2 days 1 to 3. Dose‐limiting toxicity (myelosuppression) was reached at ifosfamide 2.5 g/m2. No further Grade 3 renal toxicity was seen. Grade 3 or worse toxicities were seen as follows: neutropenia 80%, thrombocytopenia 48%, nausea/vomiting 36%, anemia 32%, renal 20%, central nervous system 16%, and infection 16%. Two toxic deaths occurred, both with infection, renal failure, and neutropenia. Partial responses were seen in 8 of 25 eligible patients (32%). Conclusions. The maximum tolerated dose in this group of patients was defined as ifosfamide 2.0 g/m2 days 1 to 3 when given with cisplatin 33 mg/m2 days 1 to 3 when combining high‐dose cisplatin with ifosfamide, it is advisable to give cisplatin in divided doses. Cancer 1993; 72:62–8. Copyright © 1993 American Cancer Society

Full Text

Duke Authors

Cited Authors

  • Graziano, SL; Herndon, JE; Richards, F; Difino, S; Modeas, C; Duggan, DB; Green, MR

Published Date

  • January 1, 1993

Published In

Volume / Issue

  • 72 / 1

Start / End Page

  • 62 - 68

Electronic International Standard Serial Number (EISSN)

  • 1097-0142

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/1097-0142(19930701)72:1<62::AID-CNCR2820720114>3.0.CO;2-E

Citation Source

  • Scopus