Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.

Objective: The aim of this study was to determine the feasibility and toxicity of concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in patients with advanced cervical cancer and other pelvic malignancies.

Methods: Eligible patients included those with large or locally advanced cervical cancer. In addition, patients with other advanced gynecologic malignancies were eligible. In part I, vinorelbine was administered as a single agent during pelvic RT at a starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5 mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20 mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week.

Results: Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium, 2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity. In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia, with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1 week in 2 of 6 patients (33%).

Conclusions: Concomitant pelvic RT and vinorelbine with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to this combination is associated with significant hematologic toxicity and is thus not a feasible approach.