Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer.
BACKGROUND
To find the maximum tolerated dose for ifosfamide in combination with paclitaxel and carboplatin in small-cell lung cancer patients (SCLC), who are resistant to cyclophosphamide, doxorubicin and etoposide (CDE).


METHODS
Different dose schedules of ifosfamide were combined with fixed doses of paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min. Included were 30 patients, with a median age of 60 years, and median time off prior cytotoxic treatment of 8 weeks. All patients were previously treated with CDE and 11 had received re-induction CDE.


RESULTS
Dose limiting toxicity of our schedule was persistent thrombocytopenia. None of the patients developed neutropenic fever. Non-haematological toxicity was mild, although two treatment-related deaths occurred. Fifty-four percent of patients had a partial response and median survival time was twenty-five weeks.


CONCLUSIONS
The maximum tolerated dose of this combination for patients with resistant SCLC is ifosfamide 2000 mg/m2 in combination with paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min administered on the first day of a 21-day cycle.
van Putten
J W
JW
Department of Pulmonary Diseases, University Hospital, Groningen, The Netherlands. j.w.g.van.putten@int.azg.nl
Kerbush
T
T
Smit
E F
EF
van Rijswijk
R
R
Beijnen
J H
JH
Sleijfer
D T
DT
Groen
H J
HJ
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced
D018906:Antineoplastic Agents, Alkylating; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide