Gemcitabine in Treating Patients with Refractory or Relapsed Multiple Myeloma

Abstract

Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve the outcome. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In gemcitabine based regimens, 3 clinical studies which including 57 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 15.7% (9/57) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia i. No treatment related death occurred with gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Runx2 Deficiency in Osteoblasts Promotes Myeloma Progression by Altering the Bone Microenvironment at New Bone Sites

“…Gemcitabine and 5-FU are FDA-approved anticancer agents used in the treatment of a variety of solid tumors (44,45), and the effects of these drugs as MDSC inhibitors in the treatment of solid cancers have been reported (18)(19)(20)(21). However, gemcitabine and 5-FU are not commonly used as anti-multiple myeloma drugs in patients, although they are occasionally used in patients with relapsed or refractory multiple myeloma (46)(47)(48). Because we have demonstrated that gemcitabine and 5-FU can restore BM immunity by depleting MDSCs in the BM in both nontumorbearing and tumor-bearing OB-Runx2 À/À mice, and because the doses of gemcitabine and 5-FU used in our animal experiments were significantly lower than the doses used in patients with cancer (seven times lower, 180 vs. 1250 mg/m 2 body surface area/week; ref.…”

Pooled Analysis of Pomalidomide for Treating Patients with Multiple Myeloma

“…MM is characterized by the proliferation of malignant plasma cells in bone marrow and the production of monoclonal immunoglobulin (Rollig et al, 2009). The majority of MM patients will relapse or become refractory to therapy after achieving complete remission (CR) (Genadieva-Stavric et al, 2014;Lin et al, 2014;Weng et al, 2014;Zhang et al, 2014;Zheng et al, 2014). Over the past decade, treatment for MM has been greatly improved due to autologous stem cell transplantation and new drugs (thalidomide, lenalidomide, and bortezomib).…”