Japanese Journal of Clinical Oncology 31:93-99 (2001)
© 2001 Foundation for Promotion of Cancer Research
Phase I and Pharmacological Study of Paclitaxel Given Over 3 h with Cisplatin for Advanced Non-small Cell Lung Cancer
1Thoracic Oncology Division, National Cancer Center Hospital, Tokyo and 2Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
Background: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer.
Methods: Patients received paclitaxel doses of 150–210 mg/m2 given over 3 h and cisplatin doses of 60–80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion.
Results: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hematological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m2, which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug–drug interaction between the 3 h infusion paclitaxel and cisplatin.
Conclusion: The recommended doses for further study are determined to be paclitaxel 180 mg/m2 and cisplatin 80 mg/m2. This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.
+ For reprints and all correspondence: Tomohide Tamura, Thoracic Oncology Division, National Cancer Center Hospital, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
Abbreviations: NSCLC, non-small cell lung cancer; CDDP, cisplatin; MTD, maximum tolerated dose; ECOG, Eastern Cooperative Oncology Group; WBC, white blood cell count; BUN, blood urea nitrogen; ECG, electrocardiogram; GCP, good clinical practice; CR, complete response; PR, partial response; PD, progressive disease; NC, no change; iv, intravenous; G-CSF, granulocyte colony-stimulating factor; DLT, dose limiting toxicity; PK, pharmacokinetic; UF-Pt, ultrafiltered platinum; HPLC, high-performance liquid chromatography; IS, internal standard; AUC, area under the plasma concentration–time curve; T, half time; MRT, mean residence time; Cmax, peak plasma concentration; CL, clearance; Vss, volume of distribution at steady state; NE, not evaluable
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