The multifractionated, twice-weekly dose schedule for a three-drug chemotherapy regimen : A Phase I–II study of paclitaxel, cisplatin, and vinorelbine
✍ Scribed by Jacob J. Lokich; Norwood Anderson; Murray Bern; Frank Coco; Edward Dow
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 65 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0008-543X
No coin nor oath required. For personal study only.
✦ Synopsis
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/m2/fraction. the paclitaxel dose was first fixed at 50 mg/m2/fraction, and venorelbine was delivered at 3 dose levels per fraction: 10, 7.5, and 5 mg/m2. paclitaxel then was de-escalated to 40 mg/m2/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/ m2/fraction and cisplatin at 15 mg/m2, the optimal dose fraction for vinorelbine was 7.5 mg/m2, defined as the dose that allowed > 67% of patients to complete 3 weeks (6 consecutive doses) of therapy. using paclitaxel at 50 mg/m2/fraction (cisplatin at 15 mg/m2/fraction), the optimal dose of vinorelbine was 5 mg/m2/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/m2/week), cisplatin (22 mg/m2/week), and vinorelbine (15 mg/m2/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/m2/fraction or 40, 15, and 7.5 mg/m2/fraction in this twice-weekly, multifractionated dose schedule.