Objectives: MM is an incurable disease with a median survival of 3 years although >50% of patients respond to initial therapy. We have previously shown that the combination of Gemzar and taxol act synergistically in vitro, to induce apoptosis and effectively kill myeloma cells in doses 5-10 fold lower than the doses required as single agents. Based on these preclinical results and a phase I-II trial in patients with solid tumors, we initiated a phase I-II clinical trial for treatment of refractory MM patients using 150mg/m2 of paclitaxel. infused over a period of 3 hours, followed by infusion of Gemzar 3,000mg/ m2 for 30-60 minutes. This regimen was administered every two weeks for a total of six cycles. The purpose of the study was to evaluate treatment-related toxicity and determine response-rate to this therapy. Results: Most patients in this study were refractory or relapsed post autologous stem cell transplantation. Of the 9 patients enrolled to date, 7 were évaluable. Since the first 2 pts had severe pancytopenia. the dose of Gemzar was lowered to 2,000 mg/m2. Lowering the dose of Gemzar resulted in tolerable grade 1 -2 hematological toxicity and with only very low incidence of grade 1-2 organ toxicities, in the rest of the patients. Of the 7 évaluable pts, 4 had a PR, 1 had a MR, 1 is responding well in the first month of chemotherapy and 1 did not respond. At this point, 6 responders completed 6 cycles of treatment and of those responders, 3 pts had 70-90% durable (3-6 months) decrease in their M-spike and a similar decrease in 2-microglobulin (2-m) and I pt had >50% decrease in M-spike and 2-m. In all responding pts, Ca++ levels returned to normal or remained stable and BM plasma cells were reduced by >50%. A fifth patient had >25% decrease in M-spike and 2-m and remained in stable disease for 2 months after treatment. One patient had grade 4 neutropenia despite dose reduction of taxol and GEMZAR and did not respond. The pt who is less than 1 month post initiation has experienced a 25% decrease in his M-protein. Conclusions: 1. Treatment was well tolerated. 2. We have observed objective responses (PR+MR by SWOG criteria) in 4 of 6 évaluable patients who have received 6 cycles of Gemzar and taxol. The full impact of this novel treatment will be determined upon further patient's accrual.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology