Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

BACKGROUNDAmbulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODSIn this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deepvein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTSOf 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONSIn high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials .gov number, NCT02555878.

Epoetin alfa is effective in improving the functional status and quality of life in anemic cancer patients receiving chemotherapy, as well as increasing hemoglobin level and decreasing transfusion requirements. Improvement in functional status can be attributed to an increase in hemoglobin level, demonstrating that quality of life in this group of patients can be improved by aggressively treating anemia. Further studies will be required to define the optimal doses and schedules for epoetin alfa.

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IntroductionMultiple myeloma (MM) or plasma cell myeloma is characterized by latent accumulation of secretory plasma cells with a low proliferative index and an extended life span in the bone marrow. 1 The second most prevalent hematologic cancer after non-Hodgkin lymphoma, multiple myeloma accounts for 10% of all hematologic cancers and approximately 2% of all cancer deaths. Conventional therapy for multiple myeloma involves combinations of vincristine, carmustine (bischloroethylnitrosourea), melphalan, cyclophosphamide, doxorubicin (Adriamycin), and prednisone or dexamethasone. 2 Patients younger than 65 years are usually given high-dose melphalan with autologous stem cell support, and older patients or those who cannot tolerate such intensive treatment are given standard-dose oral melphalan and dexamethasone. Shortcomings of these treatments are low remission rates (about 5%), short survival times (median, 30-36 months), and the development of drug resistance. 3,4 Chemoresistance remains a major therapeutic challenge in MM. The precise mechanism underlying chemoresistance in multiple myeloma is not clear, but one of the main contributors to both chemoresistance and pathogenesis is thought to be activation of NF-B and STAT3 and dysregulation of apoptosis. [4][5][6][7][8] Overexpression of antiapoptotic molecules has been linked to chemoresistance in MM; in one study, expression of the antiapoptotic protein Bcl-xL correlated with chemoresistance, with chemoresponse rates of 83% to 87% among non-Bcl-xL-expressing cases but only 20% to 31% among Bcl-xL-expressing cases. 9 Chemoresistance in several types of cancer has been linked to activation of NF-B, a transcription factor with central roles in the regulation of cell growth, survival, angiogenesis, cell adhesion, and apoptosis. 10 Progression and chemoresistance are also thought to involve interleukin 6 (IL-6), expression of which is induced by NF-B, through its regulation of the growth and survival of tumor cells. 11,12 IL-6 leads to constitutive activation of STAT3, which in turn results in expression of high levels of Bcl-xL. 6 Bcl-2 overexpression, another important characteristic of many multiple myeloma cell lines, 13 can rescue cells from glucocorticoid-induced apoptosis. 4 Cell lines resistant to doxorubicin (eg, RPMI 8226-Dox-40) have been shown to overexpress Bcl-xL. 9 Thus, both constitutive activation of NF-B and STAT3 play an important role in chemoresistance, and inhibition of NF-B and STAT3 may overcome this chemoresistance.The use of natural agents may be able to overcome resistance without some of the debilitating side effects of conventional chemotherapy. One such agent is resveratrol, a polyphenol (trans-3, The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on March 22, 2019. by guest www.bloodjournal.org From 4Ј, 5-trihydroxystilbene) abundant in red grape...