Hematology

Weekly bortezomib in combination with temsirolimus in relapsed or refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study Ghobrial, I. M. et al. Lancet Oncol. 12, 263–272 (2011)

Multiple myeloma is a prevalent and incurable disease. However, a recent phase I–II study assessed the mTOR inhibitor temsirolimus in combination with bortezomib in patients with relapsed or refractory multiple myeloma and produced some encouraging results. In the phase I part of the study, the maximum tolerated dose was established and this was used to assess efficacy in the phase II trial. Of the 44 patients enrolled, 33% achieved a partial response or better on the combination therapy, in the absence of steroids. The most common grade 3 or 4 side effects were thrombocytopenia, lymphopenia, neutropenia, leucopenia, anemia and diarrhea.

Experimental therapies

Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice García-Martínez, J. M. et al. Br. J. Cancer doi: 10.1038/bjc.2011.83

In the majority of cancers, the PI3K/mTOR pathway is activated, providing a promising antitumor target. Inhibitors of these kinases are undergoing clinical trials including the mTOR inhibitor AZD8055 and the PI3K inhibitor GDC-0941. These two agents have been assessed for efficacy in a spontaneous tumor mouse model of B-cell follicular lymphoma. Both agents reduced tumor volume by up to 50%, as well as reducing tumor cell proliferation and promoting apoptosis. However, when treatment was halted, the tumors grew back at the same rate as the untreated tumors. This finding indicates that these agents are promising but should likely be considered for combination therapies.

Targeted therapies

Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer O'Malley, D. M. et al. Gynecol. Oncol. doi:10.1016/j.ygyno.2011.01.009

Patients with recurrent epithelial ovarian cancer have shown responses when treated with weekly paclitaxel and with the angiogenesis inhibitor bevacizumab. The present study sought to determine if a combination of these therapies would improve outcomes. An institutional review of 29 patients treated with weekly paclitaxel and 41 patients treated with the combination showed a significant increase in progression-free survival and a trend towards improved overall survival in those receiving the combination. In this heavily pretreated patient population these observations are promising for determining optimal care.