title: A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer.
abstract: This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital: 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hkkunito@gan2.ncc.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Kusaba
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Sekine
authors.forename: Y
authors.initials: Y
authors.lastname: Ohe
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Shinkai
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Niho
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: N
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide