title: Ifosfamide plus high-dose cisplatin in patients with non-small cell lung cancer previously treated with chemotherapy.
abstract: This study determined the maximum tolerated dose (MTD) of ifosfamide that could be given with high-dose cisplatin to non-small cell lung cancer (NSCLC) patients previously treated with non-platin-containing chemotherapy and to assess the efficacy of this combination. Twenty-three patients with inoperable NSCLC treated with one prior chemotherapy regimen received continuous infusion ifosfamide 1.2 g/m2 per day with MESNA for 5 days every 35 days and cisplatin 120 mg/m2. After one patient who received cisplatin as a single dose developed grade 4 nephrotoxicity and myelosuppression, cisplatin was given in four divided doses (30 mg/m2 per day) and the ifosfamide dose was lowered to 1.0 g/m2 per day, infused over 4 days. Dose-limiting grades 3 and 4 leukopenia was seen in 43%. A major objective response rate of 9% was observed. The 1-year survival was 30%, with a median survival of 6.4 months. The MTD of ifosfamide administered with cisplatin (30 mg/m2 per day for 4 consecutive days) to this population of patients is 1.0 g/m2 daily for 4 days. This combination produced limited anticancer activity and significant toxicity. Excessive toxicity was observed when cisplatin was given as a single dose with ifosfamide, and this schedule should not be used.
authors.affiliation: Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Miller
authors.forename: J R
authors.initials: JR
authors.lastname: Rigas
authors.forename: K M
authors.initials: KM
authors.lastname: Pisters
authors.forename: S C
authors.initials: SC
authors.lastname: Grant
authors.forename: D G
authors.initials: DG
authors.lastname: Pfister
authors.forename: R T
authors.initials: RT
authors.lastname: Heelan
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D015080:Mesna; D002945:Cisplatin; D007069:Ifosfamide