Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer.

BACKGROUND: Previous studies have evaluated 3-week and weekly docetaxel schedules in patients with metastatic breast cancer (MBC). The varying efficacy results and toxicity profiles noted in these earlier studies led to a comparison of the schedules to determine which was safer and more efficacious. METHODS: A phase 3 clinical trial was conducted in patients with MBC who were treated with docetaxel either every 3 weeks or once weekly to determine and compare response rate and duration, time to disease progression, progression-free survival (PFS), overall survival (OS), and toxicity. Patients were randomized to receive docetaxel at a starting dose of either 75 mg/m(2) every 3 weeks or 35 mg/m(2) weekly for 3 consecutive weeks followed by 1 week of rest. RESULTS: A total of 118 patients underwent efficacy analysis; 59 patients were randomized to the every-3-week treatment arm and 59 to the weekly arm. The response rate was 35.6% (95% confidence interval [95% CI], 23.6-49.1%) for the every-3-week arm versus 20.3% (95% CI, 11.0-32.8%) for the weekly arm. There was no statistical difference between the every 3-week and the weekly treatment arms with regard to median PFS (5.7 months vs 5.5 months; P= .46) or OS (18.3 months vs 18.6 months, respectively; P= .34). There was a higher overall toxicity rate (grades 3 and 4, according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) in the every-3-week treatment arm versus the weekly treatment arm (88.1% vs 55.9%, respectively; P= .0001). CONCLUSIONS: Compared with patients who received weekly docetaxel, those who received docetaxel every 3 weeks had a higher response rate but experienced similar PFS and OS and a more pronounced toxicity.

Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy.

BACKGROUND: The current study was conducted to report the severity and management of canalicular and nasolacrimal duct stenosis as a side effect of docetaxel therapy and to report the outcomes of surgical intervention for this condition. METHODS: The records of 148 patients with epiphora associated with docetaxel therapy who were evaluated at the Ophthalmology Service at The University of Texas M. D. Anderson Cancer Center were reviewed. The frequency of docetaxel administration, the dose intensity, the cumulative dose of docetaxel, and any concomitant chemotherapeutic agents were recorded. Each patient underwent an ophthalmologic examination and in-office probing and irrigation. The patients either were treated with topical steroids or offered a surgical procedure for canalicular stenosis- (silicone intubation, dacryocystorhinostomy [DCR] with the placement of silicone tubes, or DCR with the placement of Pyrex glass tubes), depending on the severity of the canalicular stenosis. RESULTS: Docetaxel was given weekly in 71 patients, every 2 weeks in 5 patients, and every 3 weeks in 72 patients. Thirty patients (59 eyes) who received weekly docetaxel underwent surgery to correct epiphora. Twenty-three patients (39 eyes) were treated with temporary silicone tube placement, 9 patients (13 eyes) were treated with DCR with temporary silicone tube placement, and 4 patients (7 eyes) were treated with DCR with permanent Pyrex glass tube placement. Twenty-nine of the 30 patients who underwent surgery reported improvement or total resolution of epiphora after the procedure. Ten additional patients (20 eyes) who received weekly docetaxel had complete closure of their canaliculi but elected not to undergo surgery. Of special note were two patients who received weekly docetaxel in the neoadjuvant setting and developed complete closure of the canaliculi. Of the patients who received docetaxel every 2 or 3 weeks, only 3 required a surgical intervention to correct epiphora; none required Pyrex glass tube placement. CONCLUSIONS: Canalicular and nasolacrimal duct obstruction is a common side effect of weekly docetaxel therapy and can occur even when this drug is used in the neoadjuvant setting. The results of the current study indicate that early temporary silicone intubation in symptomatic patients receiving weekly docetaxel can prevent further closure of the lacrimal drainage apparatus and obviate more involved surgical interventions and permanent Pyrex glass tube placement. Cancer 2003;98:504-7.