Changes in the Mean Corpuscular Volume after Capecitabine Treatment are Associated with Clinical Response and Survival in Patients with Advanced Gastric Cancer
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidenceof capecitabine-induced macrocytosis and its association with chemotherapy outcomes,we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolledin a randomized chemotherapy trial involving capecitabine. Materials and MethodsChemotherapy-naïve AGC patients were treated with capecitabine (1,000 mg/m2/day ondays 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day1). Complete blood counts including MCV were measured at baseline and on day 1 of each3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL frombaseline. Multivariate Cox proportional hazards models were used for analysis of the impactof clinical and MCV values on chemotherapy outcomes. ResultsAt 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 elevationafter capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. Results of multivariate analysis showed that development of macrocytosis wasindependent of baseline hemoglobin level, liver metastasis, performance status, or liverfunction. The number of chemotherapy cycles showed strong association with developmentof macrocytosis and hematologic adverse events. In addition, a significant association wasobserved between macrocytosis and clinical response or survival. ConclusionMacrocytosis developed with more frequent and prolonged use of capecitabine. It is possiblethat association with treatment outcomes warrants further investigation.
Abstract
Purpose Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidenceof capecitabine-induced macrocytosis and its association with chemotherapy outcomes,we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolledin a randomized chemotherapy trial involving capecitabine. Materials and MethodsChemotherapy-naïve AGC patients were treated with capecitabine (1,000 mg/m2/day ondays 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day1). Complete blood counts including MCV were measured at baseline and on day 1 of each3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL frombaseline. Multivariate Cox proportional hazards models were used for analysis of the impactof clinical and MCV values on chemotherapy outcomes. ResultsAt 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 elevationafter capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. Results of multivariate analysis showed that development of macrocytosis wasindependent of baseline hemoglobin level, liver metastasis, performance status, or liverfunction. The number of chemotherapy cycles showed strong association with developmentof macrocytosis and hematologic adverse events. In addition, a significant association wasobserved between macrocytosis and clinical response or survival. ConclusionMacrocytosis developed with more frequent and prolonged use of capecitabine. It is possiblethat association with treatment outcomes warrants further investigation.
참고문헌 (14)
- Twelves C., "Can capecitabine replace 5-FU", leucovorin in combination with oxaliplatin for the treatment of advanced colorectal cancer?, 2002, pp.16(12 Suppl No. 14), 23~26
- Okines A, "Capecitabine in gastric cancer", Drugs Today(Barc), 44, pp.629~640 (2008)
- Borner MM, "Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin : a randomised crossover trial in advanced colorectal cancer", Eur J Cancer, 38, pp.349~358 (2002)
- Midgley R, "Capecitabine: have we got the dose right?", Nat Clin Pract Oncol, 6, pp.17~24 (2009)
- Karvellas CJ, "Effect of capecitabine on mean corpuscular volume in patients with metastatic breast cancer", Am J Clin Oncol, 27, pp.364~368 (2004)
- Sun JF, "Safety of chronic low-dose capecitabine as maintenance therapy in gastrointestinal cancers", Gastrointest Cancer Res, 3, pp.134~140 (2009)
- Wenzel C, "Capecitabine treatment results in increased mean corpuscular volume of red blood cells in patients with advanced solid malignancies", Anticancer Drugs, 14, pp.119~123 (2003)
- Scott JM, "Drug-induced megaloblastic change", Clin Haematol, 9, pp.587~606 (1980)
- Vrecl R, "Effect of capecitabine on mean corpuscular volume of red blood cells", Am J Clin Oncol, 28, pp.534~ (2005)
- van Triest B, "Prognostic role of thymidylate synthase, thymidine phosphorylase", platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer, 2000, pp.6, 1063~1072
- Yun J, "A randomised phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine(ECX)or cisplatin and capecitabine(CX)in advanced gastric cancer", Eur J Cancer, 46, pp.885~891 (2010)
- Therasse P, "New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada", J Natl Cancer Inst, 92, pp.205~216 (2000)
- Park SH, "Anemia is the strongest prognostic factor for outcomes of 5-fluorouracil-based first-line chemotherapy in patients with advanced gastric cancer", Cancer Chemother Pharmacol, 57, pp.91~96 (2006)
- Allegra CJ, "Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer", J Clin Oncol, 20, pp.1735~1743 (2002)