title: A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.
abstract: A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
authors.affiliation: Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Strauss
authors.forename: T J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: A D
authors.initials: AD
authors.lastname: Elias
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.forename: L N
authors.initials: LN
authors.lastname: Shulman
authors.forename: R W
authors.initials: RW
authors.lastname: Carey
authors.forename: M L
authors.initials: ML
authors.lastname: Grossbard
authors.forename: S
authors.initials: S
authors.lastname: Jauss
authors.forename: D J
authors.initials: DJ
authors.lastname: Sugarbaker
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D015331:Cohort Studies; D004361:Drug Tolerance; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide