Hypoalbuminemia for the prediction of venous thromboembolism and treatment of direct oral anticoagulants in metastatic gastric cancer patients
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Venous thromboembolism (VTE) is highly associated with advanced gastric cancer (AGC) and is sometimes lethal. Predictors of VTE have not been identified, and the efficacy and safety of direct oral anticoagulants (DOACs) for AGC-associated VTE remain to be clarified.
A total of 188 AGC patients who started chemotherapy during the period from January 2014 to December 2017 in our institutions were retrospectively examined for the incidence of VTE, risk factors for VTE, and the efficacy and safety of DOAC-based anticoagulant therapy for VTE.
Thirty-four patients (18%) were diagnosed with VTE at the start or during the course of chemotherapy (VTE group). More VTE group patients had a history of abdominal surgery and had moderate–severe ascites (32% versus 17%, 32% versus 14%, respectively) than non-VTE group patients (NVTE group). The mean serum albumin concentrations in the VTE group were significantly lower than NVTE group (3.38 mg/dL vs 3.65 mg/dL, respectively). Multivariate analysis showed that hypoalbuminemia was significantly correlated with VTE (P = 0.012). In the VTE group, 29 patients (85%) received anticoagulant therapy, including 24 patients treated with DOACs. No lethal VTE was observed in any patients. Thirteen patients (45%) terminated DOACs because of anemia or bleeding events, of whom eleven developed major bleeding. Median overall survivals of the VTE and NVTE groups were 9.63 months and 11.5 months, respectively (P = 0.262).
Hypoalbuminemia appears to be a risk factor for AGC-associated VTE. DOACs are effective to AGC-associated VTE, but careful observation of bleeding events is required.
KeywordsVenous thromboembolism Gastric cancer Hypoalbuminemia Direct oral anticoagulants Bleeding
Compliance with ethical standards
Conflict of interest
M. Kono has received grants from Pfizer Japan Inc. M. Fukata has received grants from Shino-Test Corporation; personal fees from Pfizer, Daiichi Sankyo Company, Bayer Yakuhin, and Boehringer Ingelheim. T. Esaki has received grants and personal fees from Eli Lilly, Taiho, Daiichi-Sankyo, Merck Serono, and Ono; grants from Novartis, DS pharma, MSD and Boehringer; personal fees from Chugai, Bristol, Eisai and Takeda. K. Akashi has received grants and personal fees from Mitsubishi Tanabe Pharma Corporation, Daiichi-Sankyo, MSD, Eisai, Astellas Pharma, Sanofi, Chugai Pharmaceutical, Asahi Kasei Pharma, Kyowa Hakko Kirin, Sumitomo Dainippon Pharma, Bristol-Myers Squibb, Takeda Pharmaceutical, Novartis Pharma, Alexion Pharmaceuticals, Teijin Pharma, Nippon Shinyaku, Yakult Honsha, Mundipharma and Bayer Yakuhin; grants from Ono Pharmaceutical, Merck Serono, Toyama Chemical, Taiho Pharmaceutical, Otsuka Pharmaceutical, Yakult Honsha Co, AbbVie, Shionogi, Eli Lilly Japan, Taisho Toyama Pharmaceutical, Mochida Pharmaceutical, The Chemo-Sero-Therapeutic Research Institute., Merck Serono, Nippon Kayaku, Japan Blood Products Organization, and Shin Nippon Biomedical Laboratories; personal fees from Celgene, Janssen Pharmaceutical, Pfizer, Medical Review, Amgen Astellas Biopharma and Shire Japan. E. Baba has received grants, personal fees and non-financial support from Eli Lilly Japan; grants and personal fees from Daiichi-Sankyo, Bristol-Myers Squibb, Taiho Pharmaceutical. Eisai, Yakult Honsha, and Ono Pharmaceutical; grants from Bayer Yakuhin, MSD, Linical; personal fees from Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Kyowa Hakko Kirin, Sanofi, Merck Serono, Tsumura, Chugai Pharmaceutical, and Astellas Pharma. All of the remaining authors declare that they have no conflicts of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
Informed consent or substitute for it was obtained from all patients for being included in the study.
- 2.Japanese Gastric Cancer Association. Japanese gastric cancer treatment guideline 2018 (ver.5). Kanehara. 2018Google Scholar
- 3.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.CrossRefGoogle Scholar
- 4.Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefGoogle Scholar
- 5.Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.CrossRefGoogle Scholar
- 7.Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefGoogle Scholar
- 17.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology Cancer-associated venous thromboembolic disease. Version 2. 2018. https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf
- 22.Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014. https://doi.org/10.1016/S2352-3026(14)70018-3.Google Scholar
- 35.Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost. 2005;94:362–5.Google Scholar