Dose-escalation study of weekly 1-hour paclitaxel administration in patients with refractory cancer

To evaluate the safety and efficacy of weekly low-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory cancer, participating subjects received standard prophylactic medication followed by intravenous paclitaxel once a week for 3 weeks every 4 weeks. The 50-mg/m2 starting dose was increased by 10 mg/m2 for every five patients, as long as no dose-limiting toxicity had occurred in more than two of five patients treated at the preceding level. Eligibility criteria included metastatic and refractory malignant disease; an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; and adequate hematologic, hepatic, and renal functions. Of 30 patients treated and evaluable for toxicity, 25 were evaluable for response. The majority of patients tolerated the treatment very well. In a total of 114 cycles, the worst toxicities observed were leukopenia (one grade 4, two grade 3), granulocytopenia (one grade 3, one grade 4), anemia (one grade 3, two grade 2), and infection (one grade 5, one grade 3). Three patients had grade 2 gastrointestinal toxicity and three had grade 1 peripheral neuropathy. Only one dose-limiting toxicity, at 100 mg/m2, has occurred. This patient died of bilateral pneumonia with neutropenia. We have observed partial responses in seven of 12 patients with breast cancer and three of eight with non-small cell lung cancer. The study remains open at the current dose level of 100 mg/m2/wk. Weekly low-dose paclitaxel is well tolerated and efficacious. Further phase II studies are warranted, to continue evaluation of this schedule of paclitaxel either alone or in combination with other drugs active in paclitaxel-responsive diseases.