Potential Regional Differences for the Tolerability Profiles of Fluoropyrimidines

2008 ◽  
Vol 26 (13) ◽  
pp. 2118-2123 ◽  
Author(s):  
Daniel G. Haller ◽  
Jim Cassidy ◽  
Stephen J. Clarke ◽  
David Cunningham ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Colon Cancer ◽  
East Asia ◽  
Regional Differences ◽  
East Asian ◽  
Safety Data ◽  
Phase Iii ◽  
Asian Patients ◽  
The World ◽  
Grade 3 ◽  
East Asian Patients

PurposeWe conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability.MethodsTreatment-related safety data from three phase III clinical studies were analyzed by multivariate analysis: two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study).ResultsIn the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR.ConclusionRegional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.

scholarly journals Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2021 ◽  
Vol 52 (3) ◽  
pp. 1069-1073
Author(s):  
Shinichiro Uchiyama ◽  
Kazunori Toyoda ◽  
Byung-Chul Lee ◽  
Chia-Wei Liou ◽  
Lawrence Ka Sing Wong ◽  
...  
Keyword(s):  
East Asia ◽  
Major Bleeding ◽  
Recurrent Stroke ◽  
East Asian ◽  
Hazard Ratio ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Asian Patients ◽  
Significant Difference ◽  
East Asian Patients

Background and Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source). Methods: Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort). Results: Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41–1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57–1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32–12.01]). Conclusions: The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

Safety results of a phase III randomized trial of adjuvant treatment with 5- fluorouracil and folinic acid with or without irinotecan, in Dukes B2 and C colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4053-4053 ◽  
Author(s):  
P. Papakostas ◽  
H. P. Kalofonos ◽  
G. Pentheroudakis ◽  
E. Timotheadou ◽  
C. Papadimitriou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Adjuvant Treatment ◽  
Safety Data ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Severe Diarrhea ◽  
Number Of Patients ◽  
Group A ◽  
Grade 3

4053 Background: The aim of our phase III study was to compare the effectiveness and the toxicity profile of 5-Fluorouracil (5- FU) + folinic acid (FA) + irinotecan (CPT-11) as adjuvant chemotherapy for resectable colon cancer (Dukes B2 and C) to that of 5-FU + FA which was considered the standard treatment. Since patients are still on follow-up regarding the primary endpoint, only safety results will be presented. Methods: Eligible patients received either 5-FU (450 mg/m2 bolus) + FA (200 mg/m2, 120 min infusion) + CPT- 11 (80 mg/m2, 90 min infusion) given 4 weeks on, two weeks off for a total of 6 treatment cycles (Arm A) or 5-FU (500 mg/m2 bolus) + FA (200 mg/m2, 120 min infusion) given 6 weeks on, two weeks off for a total of 4 treatment cycles (Arm B). Results: From January 1999 to September 2004, 910 patients (pts) were enrolled in this multi-center phase III trial. Safety data are available for 826 of the 910 pts, (415 in arm A and 411 in arm B). The total number of chemotherapy courses delivered was 8,906 (92%) in arm A and 8,775 (91%) in arm B, with median courses per patient 24 in both groups. Among patients who received treatment as randomized (403 in arm A and 398 in arm B), treatment was completed in 342 pts (82%) in arm A and in 341 pts (83%) in arm B. The number of patients who discontinued the treatment was 61 (15%) in arm A and 57 (14%) in arm B. Hospitalizations because of toxic effects happened in 37 pts (9%) in arm A and in 45 pts (11%) in arm B. Three deaths occurred in both arms. Use of G-CSF was more common in arm A (94 pts, 23%) than in arm B (38 pts, 9.5%) (p< 0.001). Significantly higher grade 3/4 neutropenia was observed in group A (11% in arm A and 3% in arm B, p< 0.001). Severe diarrhea was also frequently reported in both groups. Conclusions: These data show that both regimens have comparable and manageable toxicity profiles as adjuvant treatment in colon cancer. Severe neutropenia was more often seen in arm A. No significant financial relationships to disclose.

South-East Asia study alliance guidelines on the management of acne vulgaris in South-East Asian patients

2015 ◽  
Vol 42 (10) ◽  
pp. 945-953 ◽  
Author(s):  
Chee Leok Goh ◽  
Flordeliz Abad-Casintahan ◽  
Derrick Chen Wee Aw ◽  
Roshidah Baba ◽  
Lee Chin Chan ◽  
...  
Keyword(s):  
East Asia ◽  
Acne Vulgaris ◽  
East Asian ◽  
South East Asia ◽  
Asian Patients ◽  
East Asian Patients

scholarly journals Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials

2018 ◽  
pp. 1-12
Author(s):  
Chia-Jui Yen ◽  
Kei Muro ◽  
Tae-Won Kim ◽  
Masatoshi Kudo ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Meta Analysis ◽  
East Asian ◽  
Phase Iii ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Asian Patients ◽  
Relative Risks ◽  
Phase Iii Trials ◽  
Grade 3

Purpose Several ramucirumab trials have reported a higher incidence of selected adverse events (AEs) in East Asian (EA) patients with cancer versus non-EA patients. A meta-analysis was conducted across six completed phase III trials to establish the safety parameters of ramucirumab in EA compared with non-EA patients. Materials and Methods Six global, randomized, double-blind, placebo-controlled, phase III registration trials investigating ramucirumab were assessed. Relative risks (RRs) and 95% CIs were calculated for selected all-grade and grade ≥ 3 AEs using fixed-effects and mixed-effects models. Ratio of RR and number needed to harm were calculated for AEs (all grade and grade ≥ 3) between EA and non-EA patients. Results Of 4,996 randomly assigned patients receiving ramucirumab or placebo, 802 (16.1%) were EA (ramucirumab, n = 411; placebo, n = 391) and 4,194 were non-EA (ramucirumab, n = 2,337; placebo, n = 1,857). Patient baseline characteristics were generally balanced between treatment arms in EA and non-EA patients, excluding sex and body weight. Grade ≥ 3 AEs possibly associated with ramucirumab, which were increased in EA versus non-EA patients, included neutropenia (42.1% v 25.5%, respectively) and proteinuria (3.9% v 0.6%, respectively). There was an increase in the RR of several grade ≥ 3 AEs, including hypertension and proteinuria, in ramucirumab-treated EA and non-EA patients compared with placebo. The ratio of RR revealed no significant differences between EA and non-EA patients for all-grade and grade ≥ 3 AEs. Conclusion Despite the enhanced propensity of selected AEs in EA patients relative to non-EA patients, there were no substantial differences in the RR for AEs possibly associated with ramucirumab in these phase III trials.

scholarly journals Daratumumab plus bortezomib, melphalan, and prednisone in East Asian patients with non-transplant multiple myeloma: subanalysis of the randomized phase 3 ALCYONE trial

2019 ◽  
Vol 98 (12) ◽  
pp. 2805-2814 ◽  
Author(s):  
Tomoaki Fujisaki ◽  
Takayuki Ishikawa ◽  
Hiroyuki Takamatsu ◽  
Kenshi Suzuki ◽  
Chang-Ki Min ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
East Asian ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Similar Efficacy ◽  
Korean Patients ◽  
Asian Patients ◽  
Grade 3 ◽  
East Asian Patients

Abstract In the ALCYONE trial, daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) reduced the risk of disease progression or death by 50% versus bortezomib, melphalan, and prednisone (VMP) in patients with transplant-ineligible newly diagnosed multiple myeloma. Here, we report a subanalysis of East Asian patients from ALCYONE. After a median follow-up of 17.1 and 15.9 months for Japanese (n = 50) and Korean (n = 41) patients, respectively, median progression-free survival for D-VMP versus VMP was not reached (NR) versus 20.7 months in Japanese patients and NR versus 14.0 months in Korean patients. The overall response rate for D-VMP versus VMP was 96% versus 92% in Japanese patients and 91% versus 61% in Korean patients. Using next-generation sequencing, minimal residual disease negativity at 10−5 sensitivity for D-VMP versus VMP was 33% versus 8% among Japanese patients and 17% versus 0% among Korean patients. Rates of any grade and grade 3/4 pneumonia were consistent with the rates observed for the global safety population. Similar efficacy and safety findings were observed in the combined Japanese and Korean subgroup and ≥ 75 years of age subgroup. In conclusion, D-VMP was safe and efficacious in East Asian patients, consistent with the global ALCYONE population.

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