Comparison of injectable anticoagulants for thromboprophylaxis after cancer-related surgery.

PURPOSE: The clinical and economic outcomes associated with using injectable anticoagulants for thromboprophylaxis after cancer-related surgery are evaluated. METHODS: This retrospective cohort analysis was conducted from an institutional perspective using hospital administrative data and examined patients age 18 years or older who received unfractionated heparin (UFH), enoxaparin, dalteparin, or fondaparinux after undergoing cancer-related surgery. Outcomes assessed included venous thromboembolism (VTE) and major bleeding (MB) rates; VTE-related, MB-related, and all-cause readmission rates; mean length of stay (LOS); and mean total cost of care during hospitalization. RESULTS: In the 4068 patients evaluated (1017 per group), VTE rates were similar for fondaparinux compared with the other anticoagulants. The risk of MB was 80% higher for enoxaparin (p = 0.035) and 2.5 times higher for UFH (p = 0.0004) but not significantly higher for dalteparin compared with fondaparinux. The mean LOS was 8% longer for patients taking enoxaparin (p = 0.03) and dalteparin (p = 0.0494) and 21% longer for those treated with UFH (p < 0.0001) compared with fondaparinux. The unadjusted mean ± S.D. total cost of care per patient was lower in the fondaparinux group compared with the enoxaparin and UFH groups but higher compared with dalteparin. CONCLUSION: A retrospective evaluation of hospital administrative data for patients who had received thromboprophylaxis after cancer-related surgery revealed a similar risk of VTE with fondaparinux compared with other injectable anticoagulants. Fondaparinux was associated with a lower risk of MB compared with enoxaparin and UFH but did not differ significantly from dalteparin in this regard. A shorter LOS was observed for patients who received fondaparinux compared with dalteparin, enoxaparin, and UFH. The total cost of care for patients who received fondaparinux was lower compared with enoxaparin or UFH but higher compared with dalteparin.

Efficacy, patient-reported outcomes (PROs), and tolerability of the changing therapeutic landscape in patients with metastatic prostate cancer (MPC): a systematic literature review.

OBJECTIVE: New therapies have attempted to improve on efficacy outcomes observed with docetaxel in patients with metastatic prostate cancer (MPC) who are hormone-therapy refractory or castration-resistant. In addition to the efficacy, patient-reported outcomes (PROs) and tolerability need to be assessed to define treatment benefit, as PROs measure the patient's subjective experience and can be correlated with hard outcomes. The main objective of this study was to evaluate the survival benefit of new therapies and secondary efficacy-related outcomes. Assessment of the number of studies reporting PROs and tolerability was also conducted. METHODS: A predefined search strategy was conducted on major academic/governmental databases and conference proceedings (2007-2011). Exclusion criteria were applied. RESULTS: Of 77 studies identified, 26 (34%) evaluated survival as an end point; 14 (18%) assessed PROs/tolerability. In chemotherapy-naive patients (no/minimal symptoms), median overall survival (OS) was 26 months for sipuleucel-T. In relapsed patients, the survival benefit of cabazitaxel/abiraterone was 15 months and that of enzalutamide was 18 months. Denosumab prolonged time to first on-study skeletal-related event (20.7 months denosumab, 17.1 months zoledronic acid; P = 0.0002, noninferiority; P = 0.008, superiority). Similar benefit was documented with radium-223, a new bone-targeted α-particle-emitting radiopharmaceutical. Radium-223 also significantly improved the OS (two-sided P = 0.00185). Specific to PROs, they were incorporated primarily as secondary end points, and improvements in pain response (most commonly evaluated) were variable among the agents. Last, the therapies were associated with unique toxicities requiring careful consideration. CONCLUSIONS: The results of this review demonstrate that the therapeutic landscape of MPC has changed dramatically and many therapies in MPC now show OS improvements of about 4 months in the postdocetaxel setting.

Pemetrexed therapy for malignant pleural mesothelioma.

OBJECTIVE: To review pemetrexed, a novel multi-targeted antifolate agent. DATA SOURCES: A literature search was conducted (1985-September 2004) using MEDLINE and CANCERLIT. Recent abstracts from the American Society of Clinical Oncology were also included, along with the manufacturer's information. Key words were pemetrexed, LY-231514, Alimta, multi-targeted antifolate, malignant pleural mesothelioma. STUDY SELECTION AND DATA EXTRACTION: Relevant information on pharmacology, pharmacokinetics, and safety and efficacy of pemetrexed from clinical trials was selected. DATA SYNTHESIS: Pemetrexed inhibits folate metabolism and purine/pyrimidine synthesis. Based on Phase I and II trials, pemetrexed has antitumor activity in solid tumors such as lung, colorectal, and cervical. A pivotal Phase III study in patients with malignant pleural mesothelioma (MPM) demonstrated survival superiority of pemetrexed-cisplatin regimen versus cisplatin. CONCLUSIONS: Pemetrexed is a promising new drug for the treatment of solid malignancies, most notably MPM.