A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients

Y. Gazitt, G. David Roodman, C. Freytes, P. Shaughnessy, N. Callander, A. Traynor, M. Rothenberg

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000
Externally publishedYes

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gemcitabine
Phase II Clinical Trials
Clinical Trials, Phase I
Paclitaxel
Multiple Myeloma
Refractory materials
Toxicity
Therapeutics
Chemotherapy
Stem cells
Tumors
Apoptosis
Plasmas
Pancytopenia
Stem Cell Transplantation

ASJC Scopus subject areas

  • Hematology

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A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients. / Gazitt, Y.; Roodman, G. David; Freytes, C.; Shaughnessy, P.; Callander, N.; Traynor, A.; Rothenberg, M.

In: Blood, Vol. 96, No. 11 PART II, 2000.

Research output: Contribution to journalArticle

Gazitt, Y, Roodman, GD, Freytes, C, Shaughnessy, P, Callander, N, Traynor, A & Rothenberg, M 2000, 'A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients', Blood, vol. 96, no. 11 PART II.
Gazitt, Y. ; Roodman, G. David ; Freytes, C. ; Shaughnessy, P. ; Callander, N. ; Traynor, A. ; Rothenberg, M. / A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients. In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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abstract = "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 {\'e}valuable. 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 {\'e}valuable 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 {\'e}valuable 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.",
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T1 - A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients

AU - Gazitt, Y.

AU - Roodman, G. David

AU - Freytes, C.

AU - Shaughnessy, P.

AU - Callander, N.

AU - Traynor, A.

AU - Rothenberg, M.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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