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A phase I trial of ifosfamide, mesna, and cisplatin in advanced non‐small cell lung cancer a cancer and leukemia group B study
Author(s) -
Graziano Stephen L.,
Herndon James E.,
Richards Frederick,
Difino Santo,
Modeas Caron,
Duggan David B.,
Green Mark R.
Publication year - 1993
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19930701)72:1<62::aid-cncr2820720114>3.0.co;2-e
Subject(s) - mesna , medicine , ifosfamide , lung cancer , cisplatin , oncology , cancer , leukemia , chemotherapy
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/m 2 given on day 1. Seven patients were treated with ifosfamide 2.0 g/m 2 days 1 to 3, and six patients received ifosfamide 2.5 g/m 2 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/m 2 ). 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/m 2 days 1–3) and dose level 4 (ifosfamide 2.5 g/m 2 days 1–3) with cisplatin 33 mg/m 2 days 1 to 3. Dose‐limiting toxicity (myelosuppression) was reached at ifosfamide 2.5 g/m 2 . 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/m 2 days 1 to 3 when given with cisplatin 33 mg/m 2 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.