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The multifractionated, twice‐weekly dose schedule for a three‐drug chemotherapy regimen
Author(s) -
Lokich Jacob J.,
Anderson Norwood,
Bern Murray,
Coco Frank,
Dow Edward
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990115)85:2<499::aid-cncr31>3.0.co;2-v
Subject(s) - vinorelbine , medicine , regimen , paclitaxel , cisplatin , chemotherapy , neutropenia , toxicity , pharmacology , urology , surgery
BACKGROUND Paclitaxel, cisplatin, and vinorelbine are three important antineoplastic drugs with different mechanisms of cell kill. A combination of these three drugs potentially could have additive therapeutic effects. METHODS The three‐drug combination (designated TPN) was administered on a twice‐weekly (Monday/Thursday; Tuesday/Friday) schedule for 3 weeks, with cycles repeated every 28 days. The Phase I design utilized a dose de‐escalation schema in which the maximum tolerated dose was defined by a patient's ability to complete 6 doses (a full cycle) without interruption for hematologic Grade 3 or 4 toxicity. RESULTS Twenty‐seven patients received a total of 42 evaluable courses of the 3‐drug regimen. The cisplatin dose was fixed at 15 mg/M 2 /fraction. The paclitaxel dose was first fixed at 50 mg/M 2 /fraction, and venorelbine was delivered at 3 dose levels per fraction: 10, 7.5, and 5 mg/M 2 . Paclitaxel then was de‐escalated to 40 mg/M 2 /fraction, and the same 3 dose levels of vinorelbine were evaluated. The dose‐limiting toxicity was neutropenia. Using fixed doses of paclitaxel at 40 mg/M 2 /fraction and cisplatin at 15 mg/M 2 , the optimal dose fraction for vinorelbine was 7.5 mg/M 2 , defined as the dose that allowed > 67% of patients to complete 3 weeks (6 consecutive doses) of therapy. Using paclitaxel at 50 mg/M 2 /fraction (cisplatin at 15 mg/M 2 /fraction), the optimal dose of vinorelbine was 5 mg/M 2 /fraction. Tumor responses were observed in 13 patients: 2 with unknown primary, 1 with esophageal carcinoma, 6 with nonsmall cell lung carcinoma, and 3 with breast carcinoma. Grade 2 neurologic (sensory) toxicity was observed in 5 patients. CONCLUSIONS TPN administered according to a twice‐weekly dosing scheme can be delivered with acceptable toxicity. The dose intensity for paclitaxel (60–75 mg/M 2 /week), cisplatin (22 mg/M 2 /week), and vinorelbine (15 mg/M 2 /week) is > 50% of the single agent dose intensity for the component agent. Recommended Phase II or Phase III trials could utilize dose fractions of paclitaxel, cisplatin, and vinorelbine at either 50, 15, and 5 mg/M 2 /fraction or 40, 15, and 7.5 mg/M 2 /fraction in this twice‐weekly, multifractionated dose schedule. Cancer 1999;85:499–503. © 1999 American Cancer Society.