Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984). The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power. No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within the HCT subgroup revealed significant improvement in outcomes in delayed and overall phases with FOND-O in the autologous but not allogeneic cohort. Addition of olanzapine to an NK-1-based triplet antiemetic regimen significantly improved clinically relevant outcomes in the HCT population.
The earthquake that occurred in Taiwan on 21 September 1999 killed >2,000 people and severely injured many survivors. Despite the large scale and sizeable impact of the event, a complete overview of its consequences and the causes of the inadequate rescue and treatment efforts is limited in the literature. This review examines the way different groups coped with the tragedy and points out the major mistakes made during the process. The effectiveness of Taiwan's emergency preparedness and disaster response system after the earthquake was analyzed.Problems encountered included: (1) an ineffective command center; (2) poor communication; (3) lack of cooperation between the civil government and the military; (4) delayed prehospital care; (5) overloading of hospitals beyond capacity; (6) inadequate staffing; and (7) mismanaged public health measures.The Taiwan Chi-Chi Earthquake experience demonstrates that precise disaster planning, the establishment of one designated central command, improved cooperation between central and local authorities, modern rescue equipment used by trained disaster specialists, rapid prehospital care, and medical personnel availability, as well earthquake-resistant buildings and infrastructure, are all necessary in order to improve disaster responses.
Risk stratification in acute myeloid leukemia (AML) remains principle for survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. The complexity of risk stratification and comparative outcomes between the 2022 and 2017 ELN guidelines remains unknown. This comparative analysis evaluated outcomes between the 2017 and 2022 ELN criteria in patients enrolled within the multi-center Beat AML cohort. Five-hundred thirteen patients were included. Most patients had one (36% [N=183]) or two (31% [N=159]) ELN risk-defining abnormalities. In patients with two or more ELN-risk defining mutations (58% [N=297]), 44% (N=132) had mutations spanning multiple ELN risk categories. Compared to ELN 2017 criteria, the updated ELN 2022 guidelines changed assigned risk group in 15% (N=75) of patients, including 10% (N=16/160), 26% (N=29/112), and 6% (N=13/224) of ELN 2017 favorable, intermediate, and adverse-risk patients. Median OS across ELN 2022 favorable, intermediate, and adverse-risk groups was not reached (estimated 5-year OS: 53% [standard error: 0.06%]), 16.8 (95% CI: 11-48) and 9.7 (95% CI: 8.3-10.8) months, respectively. The ELN 2022 guidelines more accurately stratified survival between patients with intermediate or adverse-risk AML treated with IC (HR: 1.58 [95% CI: 1.12-2.25], p-value: 0.01) compared to ELN 2017 guidelines (HR 1.27 [95% CI: 0.88-1.85], p-value: 0.20). The updated ELN 2022 guidelines better stratify survival, namely between patients with intermediate or adverse-risk AML treated with IC. The increased complexity of risk stratification with inclusion of additional cytogenetic and molecular aberrations necessitates clinical workflows simplifying risk stratification.
Cobimetinib combined with vemurafenib is an alternative BRAF/MEK inhibitor therapy for unresectable or metastatic melanoma with BRAFV600 mutation. The role of cobimetinib in melanoma and other solid tumors is likely to expand as the results from ongoing studies become available.
Background Patients with gynecologic malignancies are at an increased risk for venous thromboembolism. National guidelines recommend treatment of an acute venous thromboembolism with low molecular weight heparin for 5-10 days followed by long-term secondary prophylaxis with low molecular weight heparin for at least six months. Non-vitamin K oral anticoagulants are not currently recommended to be used in cancer patients for the management of venous thromboembolism because robust data on their efficacy and safety have yet to become available in cancer patients. The objectives of this study were to determine the proportion of gynecologic oncology patients with venous thromboembolism using rivaroxaban compared to warfarin or low molecular weight heparin as well as compare the safety and efficacy of these anticoagulants. Methods This study was a retrospective pilot analysis of adult patients with gynecologic malignancies who received either rivaroxaban, warfarin or low molecular weight heparin for treatment of venous thromboembolism at Augusta University Medical Center from 1 July 2013 to 30 June 2015. Statistical comparisons between the enoxaparin and rivaroxaban group were made using T-tests and Chi-square or Fisher's exact tests, where appropriate. Results Out of the 49 patients, 37% (18) patients were on rivaroxaban, 53% (26) on enoxaparin, and 10% (5) on warfarin. Only one patient (4%) in the enoxaparin group experienced a recurrent deep vein thrombosis while there were no cases of recurrent venous thromboembolism in the rivaroxaban and warfarin group. The incidence of major bleeding was 17% ( n = 2), 20% ( n = 1), and 8% ( n = 2) in patients receiving rivaroxaban, enoxaparin, and warfarin, respectively. The rate of switching to a different anticoagulant than originally prescribed was 42% ( n = 14) in the enoxaparin arm, and 5.5% ( n = 1) in the rivaroxaban arm. Conclusion A high proportion of our gynecologic oncology patients received rivaroxaban for the management of venous thromboembolism. The sample size of this pilot analysis was too small to draw any conclusions regarding efficacy and safety of rivaroxaban compared with enoxaparin and warfarin. High rate of rivaroxaban use in gynecologic oncology patients at our institution highlights the need for larger, well-designed randomized controlled trials to confirm the safety and efficacy of its use in this population.
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