BACKGROUND: Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). METHOD AND RESULTS: Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%. CONCLUSION: This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.
BACKGROUND: Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). METHOD AND RESULTS: Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%. CONCLUSION: This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.
Authors: Russell D Hull; Graham F Pineo; Rollin F Brant; Andrew F Mah; Natasha Burke; Richard Dear; Turnly Wong; Roy Cook; Susan Solymoss; Man-Chiu Poon; Gary Raskob Journal: Am J Med Date: 2006-12 Impact factor: 4.965
Authors: Clive Kearon; Elie A Akl; Joseph Ornelas; Allen Blaivas; David Jimenez; Henri Bounameaux; Menno Huisman; Christopher S King; Timothy A Morris; Namita Sood; Scott M Stevens; Janine R E Vintch; Philip Wells; Scott C Woller; Lisa Moores Journal: Chest Date: 2016-01-07 Impact factor: 9.410
Authors: Agnes Y Y Lee; Pieter W Kamphuisen; Guy Meyer; Rupert Bauersachs; Mette S Janas; Mikala F Jarner; Alok A Khorana Journal: JAMA Date: 2015-08-18 Impact factor: 56.272
Authors: Agnes Y Y Lee; Mark N Levine; Ross I Baker; Chris Bowden; Ajay K Kakkar; Martin Prins; Frederick R Rickles; Jim A Julian; Susan Haley; Michael J Kovacs; Michael Gent Journal: N Engl J Med Date: 2003-07-10 Impact factor: 91.245
Authors: Dominique Farge; Corinne Frere; Jean M Connors; Cihan Ay; Alok A Khorana; Andres Munoz; Benjamin Brenner; Ajay Kakkar; Hanadi Rafii; Susan Solymoss; Dialina Brilhante; Manuel Monreal; Henri Bounameaux; Ingrid Pabinger; James Douketis Journal: Lancet Oncol Date: 2019-09-03 Impact factor: 41.316
Authors: Paolo Prandoni; Anthonie W A Lensing; Andrea Piccioli; Enrico Bernardi; Paolo Simioni; Bruno Girolami; Antonio Marchiori; Paola Sabbion; Martin H Prins; Franco Noventa; Antonio Girolami Journal: Blood Date: 2002-07-12 Impact factor: 22.113
Authors: Nigel S Key; Alok A Khorana; Nicole M Kuderer; Kari Bohlke; Agnes Y Y Lee; Juan I Arcelus; Sandra L Wong; Edward P Balaban; Christopher R Flowers; Charles W Francis; Leigh E Gates; Ajay K Kakkar; Mark N Levine; Howard A Liebman; Margaret A Tempero; Gary H Lyman; Anna Falanga Journal: J Clin Oncol Date: 2019-08-05 Impact factor: 44.544
Authors: Guy Meyer; Zora Marjanovic; Judith Valcke; Bernard Lorcerie; Yves Gruel; Philippe Solal-Celigny; Christine Le Maignan; Jean Marc Extra; Paul Cottu; Dominique Farge Journal: Arch Intern Med Date: 2002 Aug 12-26