Phase II study of paclitaxel and estramustine in patients with recurrent and refractory non-Hodgkin lymphoma.

BACKGROUND

The current study was conducted to evaluate the efficacy of paclitaxel, administered weekly or once every 3 weeks, in combination with oral estramustine phosphate (EMP) in patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL).

METHODS

Between February 1996 and February 2001, 23 patients with recurrent NHL were enrolled onto this Phase II trial. The median age for all patients was 65 years (range, 27-80 years). The initial 12 patients (who received a mean number of 2.4 prior treatments, including 1 patient who received a prior peripheral blood stem cell transplant) received paclitaxel at a dose of 175 mg/m2 given as a 3-hour intravenous infusion every 21 days. The next 11 patients (who received a mean number of 2.8 prior treatments, including 1 patient who received prior peripheral blood stem cell transplant) were registered (1 patient refused treatment) to receive paclitaxel at a dose of 80 mg/m2 as a 1-hour intravenous infusion weekly for 6 weeks of an 8-week cycle. All patients received EMP at a dose of 600 mg/m2 orally per day beginning the day prior to each dose of paclitaxel for a total of 3 days.

RESULTS

When paclitaxel was administered every 21 days, 4 partial responses were observed in 12 evaluable patients (33.3%). The median survival was 147 days. The median duration of response was 102 days (range, 42-127 days) and the median time to disease progression was 66 days. Grade 3 and Grade 4 neutropenia (according to the revised version of the Common Toxicity Criteria of the National Cancer Institute) were observed in 5 patients (42%) in this group. In an attempt to reduce the incidence of myelosuppression, paclitaxel dosing was changed to weekly dosing. In the cohort of patients receiving weekly paclitaxel, an objective response was reported to occur in 3 (1 complete response and 2 partial responses) of 11 evaluable patients (27%). The median survival was 132 days (range, 33-462 days). The median duration of response was 64 days and the median time to disease progression was 57 days. There was no significant difference noted between the cohort receiving paclitaxel three times weekly and those receiving paclitaxel weekly with regard to overall survival and time to disease progression (P = 0.7 and P = 0.8, respectively by the log-rank test). Grade 3 or 4 neutropenia was observed in only 2 of 11 patients (18%) in the weekly paclitaxel group. There were no significant differences noted in terms of thrombocytopenia, anemia, nausea, anorexia, or fatigue between the treatment groups.

CONCLUSIONS

Paclitaxel given once weekly or three times weekly, in combination with oral EMP, was found to have comparable efficacy in patients with recurrent NHL, with an overall response rate of 30%. The response rate was found to be higher than that reported in prior studies of paclitaxel as a single agent in the treatment of NHL, suggesting that EMP may enhance paclitaxel efficacy in patients with NHL. Hematologic toxicity was diminished when paclitaxel was administered on a weekly schedule. The minimal myelotoxicity of weekly paclitaxel makes this a potentially attractive agent for combination regimens for patients with recurrent/refractory NHL.