A dose escalation study of weekly docetaxel in patients with advanced solid tumors

Purpose: To determine the maximum tolerated dose (MTD) and the dose-limitin g toxicity (DLT) of weekly administration of docetaxel for three consecutiv e weeks every 4 weeks in patients with advanced solid tumors. Patients and methods: A total of 16 patients with malignant tumors refractory to convent ional treatment were enrolled in this phase I study; their median age was 6 2 years. Of the 26 patients, 16 (62%) had previously received more than one chemotherapy regimen and 17 (65%) had previously received taxanes in a 3-w eek schedule. Docetaxel was administered after appropriate premedication at escalating doses (starting dose 30 mg/ m(2)) as a 1-h i.v. infusion for th ree consecutive weeks in cycles of 4 weeks. Results: A total of 68 chemothe rapy cycles were administered with a median of three cycles per patient (ra nge one to six). The DLT was reached at 45 mg/m(2) per week and the dose-li miting events were grade 4 neutropenia, febrile neutropenia, and treatment delay due to incomplete hematologic recovery. The MTD was defined at a dose of 42 mg/m(2)/week. Grade 3/4 neutropenia occurred in seven patients (27%) (10% of cycles), and four patients (15%) developed febrile neutropenia. Th ere were no deaths due to sepsis. Grade 2 peripheral neurotoxicity was obse rved in two patients (8%), grade 2 and 3 fatigue in 14 (54%), grade 2 edema in seven (27%), mild allergic reactions in two (8%) and lacrimation in thr ee (12%). One (4%) complete response and eight (35%) partial responses (ove rall response rate 39%) were observed in 23 evaluable patients. Stable dise ase and progressive disease were observed in six patients (26%) and eight p atients (35%), respectively. All responses were observed in patients with m etastatic breast cancer, one of whom had progressed on paclitaxel-based and two of whom had progressed on docetaxel-based chemotherapy. Conclusions: T he weekly administration of docetaxel for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and call be given on an outpatient basis. Moreover, this schedule of docetaxel administ ration seems to have an enhanced efficacy, especially in patients with adva nced breast cancer who have failed front-line taxane-based chemotherapy.