Prospective evaluation of drug-drug interactions in ambulatory cancer patients initiated on prophylactic anticoagulation.

INTRODUCTION: Drug options for VTE prophylaxis are increasing for ambulatory cancer patients and data regarding anticoagulant-drug interactions and their relationship to VTE and bleeding are needed to improve care. METHODS: Over one year, 108 cancer patients with high VTE risk were prospectively identified. Potential anticoagulant-drug interactions were ascertained by chart review and graded on need for intervention. Providers selected anticoagulant prophylaxis based on potential drug interactions and patient-provider discussion. A cross-sectional analysis was performed thereafter to evaluate VTE and bleeding endpoints within one year of anticoagulant initiation. RESULTS: The average number of potential drug interactions per patient was higher for warfarin than others (3.04 vs. 1.28 (apixaban), 1.02 (rivaroxaban), and 0.98 (LMWH)). The severity of the interactions based on grade was, for apixaban: 1.6% grade X, 50.8% grade D, and 47.5% grade C; for rivaroxaban: 2.1% grade X, 64.9% grade D, 33.0% grade C; for LMWH, 0% grade X, 66.7% grade D, 33.3% grade C; and for warfarin, 0% grade X, 29.4% grade D, 70.6% grade C. At the end of the investigational period, 11 bleeds and 7 VTEs were reported. Drug combinations significantly associated with an increased bleeding risk were crizotinib with apixaban or rivaroxaban and PPIs with warfarin. The use of sulfamethoxazole-trimethoprim with warfarin was associated with an increased VTE risk. CONCLUSIONS: DOACs had fewer DDIs than warfarin, although interaction severity differed between anticoagulants. Some anticoagulant-drug interactions were associated with bleeding or VTE. Although not powered for analysis, DDI severity did not affect bleeding rates and inversely correlated with VTE risk.

Dexamethasone premedication for prophylaxis of taxane toxicities: can the doses be reduced when paclitaxel or docetaxel are given weekly?

PURPOSE: To evaluate the clinical literature supporting reduced doses of dexamethasone to prevent taxane hypersensitivity reactions (HSRs), and edema/skin toxicities in respect to docetaxel, when taxanes are given weekly, as opposed to every 3 weeks. DATA SOURCE: Clinical literature of human-controlled clinical trials, accessed through MEDLINE and meeting abstract databases (from 1990 to 2010). DATA EXTRACTION: The retrieved literature was reviewed to include all human clinical trials that recorded adverse effect information with weekly taxanes utilizing reduced-dose or tapering dexamethasone schemas, either prospectively or retrospectively. DATA SYNTHESIS: Prophylaxis for paclitaxel-related HSRs generally includes one or more 20 mg doses of dexamethasone, with histamine-1 and -2 receptor antagonists prior to infusion of paclitaxel. Prophylaxis for docetaxel-related HSRs generally includes dexamethasone beginning 1 day before docetaxel, and continuing twice daily for a total of 3 days. These schedules were designed for taxanes given every 3 weeks, but may lead to steroid-related adverse effects when given weekly with weekly taxane administration. Treatment strategies designed to reduce corticosteroid exposure in patients receiving weekly taxanes have been investigated. CONCLUSIONS: Several predication strategies utilizing reduced doses of dexamethasone with weekly taxanes appear to be feasible and safe, and can be considered for patients experiencing, or at high risk for steroid-induced side effects. However, the optimal schedule is not yet determined; larger prospective clinical trials are needed.

Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants' Hospital.

OBJECTIVES: Carboplatin (C) is a standard treatment for gynecologic cancers, but its use in recurrence is associated with an increased risk of hypersensitivity reactions (HSR) in those previously treated with C. However, there is no way to predict those at risk for a C-HSR. We sought to evaluate whether the platinum-free interval (PFI) was predictive of incidence and severity of HSRs. METHODS: Patients treated with C between 1/99 and 12/2005 were identified through our chemotherapy database. Records were reviewed in those receiving multiple C regimens or with C HSR. Severity was defined as mild or severe based on symptoms. RESULTS: 126 patients were identified who had multiple C regimens. 63 (50%) experienced C HSRs of which 36 (29%) were severe. The incidence of C HSR was 25.8% for PFI < 12 months and 56.5% if > or = 12 months (p=0.0023). The incidence of a severe C HSR significantly increased with time as well: 6.5% PFI < 12 months, 23.9% PFI 12-24 months and 47% PFI > or = 24 months (p=0.0091). Of those receiving a 3rd regimen of C, 8/8 had a HSR and these were severe in seven (88%). Of note, 60 patients received > 8 (range 9-19) cycles with the first C regimen, and none of the patients reacted after cycle 8. CONCLUSIONS: A duration of greater than 12 months between C regimens is associated with an increased risk of both any--and severe--HSR. Our data also suggests that upfront treatment with C beyond eight cycles is not associated with an increased risk of HSR.