Purpose Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine. Materials and Methods Chemotherapy-naïve AGC patients were treated with capecitabine (1,000 mg/m2/day on days 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day 1). Complete blood counts including MCV were measured at baseline and on day 1 of each 3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL from baseline. Multivariate Cox proportional hazards models were used for analysis of the impact of clinical and MCV values on chemotherapy outcomes. Results At baseline, the mean MCV was 88.2 fL (normal range, 80 to 100 fL). During chemotherapy, MCV increased in a dose-dependent manner with a mean increase of 11.3 fL. MCV elevation after capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. Results of multivariate analysis showed that development of macrocytosis was independent of baseline hemoglobin level, liver metastasis, performance status, or liver function. The number of chemotherapy cycles showed strong association with development of macrocytosis and hematologic adverse events. In addition, a significant association was observed between macrocytosis and clinical response or survival. Conclusion Macrocytosis developed with more frequent and prolonged use of capecitabine. It is possible that association with treatment outcomes warrants further investigation.
Citations
Citations to this article as recorded by
Patient-derived tumor xenograft animal model of gastric cancer in precision chemotherapy Yiyin Zhang, Yongming Yang, Jiayi Zhou, Qianqian Yu, Lixia Chen, Lili Zhao, Yongsheng Meng, Jing Wang, Lei Yan, Ziyang Huang, Shuchen Song, Wenqi Bai, Ruifang Sun, Xihua Yang Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub] CrossRef
Comprehensive Evaluation of Frailty and Sarcopenia Markers to Predict Survival in Glioblastoma Patients Chao Yang, Chao Ma, Cheng‐Shi Xu, Si‐Rui Li, Chen Li, Ze‐Fen Wang, Zhi‐Qiang Li Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub] CrossRef
Significance of preoperative mean corpuscular volume in patients with stage II/III colorectal cancer and anemia Shuhei Asai, Hideo Miyake, Hidemasa Nagai, Yuichiro Yoshioka, Koji Shibata, Junichi Takamizawa, Norihiro Yuasa International Journal of Clinical Oncology.2025;[Epub] CrossRef
Prognostic significance of mean corpuscular volume in patients with pancreatic ductal adenocarcinoma and multimodal treatment Gerd Jomrich, Maximilian Gruber, Elisabeth S. Gruber, Jakob Mühlbacher, Sanja Radosavljevic, Lavinia Wilfing, Daniel Winkler, Gerald Prager, Christian Reiterer, Barbara Kabon, Helmuth Haslacher, Klaus Sahora, Martin Schindl Journal of Visceral Surgery.2024; 161(2): 99. CrossRef
Signification pronostique du volume globulaire moyen chez les patients ayant un traitement multimodal de l’adénocarcinome du pancréas Gerd Jomrich, Maximilian Gruber, Elisabeth S. Gruber, Jakob Mühlbacher, Sanja Radosavljevic, Lavinia Wilfing, Daniel Winkler, Gerald Prager, Christian Reiterer, Barbara Kabon, Helmuth Haslacher, Klaus Sahora, Martin Schindl Journal de Chirurgie Viscérale.2024; 161(2): 110. CrossRef
The relevance of macrocytosis induction during neoadjuvant dose-dense chemotherapy in breast cancer patients Tihana Boraska Jelavić, Mario Podrug, Marija Ban, Ingrid Belac Lovasić, Zvonimir Curić, Eduard Vrdoljak Anti-Cancer Drugs.2022; 33(1): e655. CrossRef
5-Fluorouracil enhances the chemosensitivity of gastric cancer to TRAIL via inhibition of the MAPK pathway Hui Li, Jing Lv, Jing Guo, Shasha Wang, Shihai Liu, Yingji Ma, Zhiwei Liang, Yunyun Wang, Weiwei Qi, Wensheng Qiu Biochemical and Biophysical Research Communications.2021; 540: 108. CrossRef
Platelet‐Lymphocyte ratio is a predictor for the development of no‐reflow phenomenon in patients with ST‐segment elevation myocardial infarction after thrombus aspiration Oktay ŞENÖZ, Sadık Volkan EMREN, Ahmet ERSEÇGİN, Zeynep YAPAN EMREN, İlker GÜL Journal of Clinical Laboratory Analysis.2021;[Epub] CrossRef
Selected Hematological Biomarkers to Predict Acute Mortality in Emergency Department Patients. Recent Polish Hospital Statistics Katarzyna Brzeźniakiewicz-Janus, Marcus Daniel Lancé, Andrzej Tukiendorf, Tomasz Janus, Mirosław Franków, Joanna Rupa-Matysek, Zuzanna Walkowiak, Lidia Gil Disease Markers.2020; 2020: 1. CrossRef
High Mean Corpuscular Volume Predicts Poor Outcome for Patients With Gastroesophageal Adenocarcinoma Gerd Jomrich, Marlene Hollenstein, Max John, Robin Ristl, Matthias Paireder, Ivan Kristo, Reza Asari, Sebastian F. Schoppmann Annals of Surgical Oncology.2019; 26(4): 976. CrossRef
The mean corpuscular volume as a prognostic factor for colorectal cancer Hidemasa Nagai, Norihiro Yuasa, Eiji Takeuchi, Hideo Miyake, Yuichiro Yoshioka, Kanji Miyata Surgery Today.2018; 48(2): 186. CrossRef
Mean Corpuscular Volume as a Predictive Factor of Response to Preoperative Chemoradiotherapy in Locally Advanced Rectal Cancer Wen-Yi Zhang, Xing-Xing Chen, Wen-Hao Chen, Hui Zhang, Chang-Lin Zou Gastroenterology Research and Practice.2018; 2018: 1. CrossRef
The prognostic value of interaction between mean corpuscular volume and red cell distribution width in mortality in chronic kidney disease Chew-Teng Kor, Yao-Peng Hsieh, Chia-Chu Chang, Ping-Fang Chiu Scientific Reports.2018;[Epub] CrossRef
Is macrocytosis a potential biomarker of the efficacy of dose-dense paclitaxel–carboplatin combination therapy in patients with epithelial ovarian cancer? Tihana Boraska Jelavić, Toni Boban, Luka Brčić, Eduard Vrdoljak Anti-Cancer Drugs.2017; 28(8): 922. CrossRef
Mean Corpuscular Volume is a Prognostic Factor for Patients after Curative Resection for Stage II Colorectal Cancer Takahiro HOSOI, Norihiro YUASA, Eiji TAKEUCHI, Yasutomo GOTO, Hideo MIYAKE, Hidemasa NAGAI, Yuichiro YOSHIOKA, Kanji MIYATA Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2017; 78(5): 905. CrossRef
Mean Corpuscular Volume and Mortality in Patients with CKD Yao-Peng Hsieh, Chia-Chu Chang, Chew-Teng Kor, Yu Yang, Yao-Ko Wen, Ping-Fang Chiu Clinical Journal of the American Society of Nephrology.2017; 12(2): 237. CrossRef
Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma Guo-Xing Wan, Ping Chen, Xiao-Jun Cai, Lin-Jun Li, Xiong-Jie Yu, Dong-Feng Pan, Xian-He Wang, Xuan-Bin Wang, Feng-Jun Cao Clinica Chimica Acta.2016; 452: 199. CrossRef