Profiling chemotherapy-associated myelotoxicity among Chinese gastric cancer population receiving cytotoxic conventional regimens: epidemiological features, timing, predictors and clinical impacts

Ci Zhu; Yan Wang; Xicheng Wang; Chunmei Bai; Dan Su; Bing Cao; Jianming Xu

doi:10.7150/jca.17847

Profiling chemotherapy-associated myelotoxicity among Chinese gastric cancer population receiving cytotoxic conventional regimens: epidemiological features, timing, predictors and clinical impacts

J Cancer. 2017 Aug 18;8(13):2614-2625. doi: 10.7150/jca.17847. eCollection 2017.

Authors

Ci Zhu¹, Yan Wang¹, Xicheng Wang², Chunmei Bai³, Dan Su⁴, Bing Cao⁵, Jianming Xu¹

Affiliations

¹ Beijing 307 People's Liberation Army Hospital Cancer Centre, Beijing, China.
² Department of Gastrointestinal Oncology, Beijing Cancer Hospital, Beijing, China.
³ Department of Gastrointestinal Oncology, Peking Union Medical College Hospital, Beijing, China.
⁴ Oncology Department, No. Chinese PLA General Hospital, Beijing, China.
⁵ Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Objectives: We aim to evaluate the epidemiological features, timing, predictors and clinical impacts of chemotherapy-associated myelotoxicity in Chinese gastric cancer population receiving six established cytotoxic conventional regimens (CF/XP, EC(O)F/EC(O)X, DC(O)F/DC(O)X, PC(O)F/PC(O)X, FOLFOX4, or mFOLFOX7/XELOX). Patients and methods: A 4-year multicenter, prospective, observational study was conducted in multiple hospitals/institutes spanning three major regions in China. A total of 1,285 patients with gastric cancer, treated with six selected regimens between 2010 and 2014 were included. Kaplan-meier analysis was applied to estimate the time to develop myelotoxicity events for each regimen. Multivariable logistic regression model was built to identify predictors associated with chemotherapy-induced myelotoxicity, evaluating detailed specific factors of patients, disease and treatment patterns. Results: Triplet regimens were associated with more moderate-to-severe myelotoxicity events than doublet regimens. DC(O)F/DC(O)X group presented with moderate-to-severe anaemia, thrombocytopenia, and leukopenia earlier than other regimen groups, with median time of 3.5, 4.8 and 3.3 cycles, respectively. PC(O)F/PC(O)X group had a shortest time to develop Moderate-to-Severe neutropenia (median time, 3.3 cycles). Multivariate analysis identified several independent predictors for moderate-to-severe myelotoxicity, including: baseline Hb<12.0 g/dL, male gender, KPS<80, previously treated with surgery, tumor located at gastroesophageal junction(GEJ), DC(O)F/DC(O)X regimen, palliative intent, triplet combination therapy and No. of cycles received≥4. Dose reductions≥20% occurred in 16.7% of patients and treatment delays≥7 days presented in 21.1% of patients, resulting in patients receiving an actual average Relative Dose Intensity (RDI) of 0.733. Conclusions: Myelotoxicity events were frequently observed within the gastric cancer population undertaking multicycle polychemotherapy. Predictive models based on risk factors identified for moderate-to-severe myelotoxicity should enable the targeted use of appropriate supportive care in an effort to facilitate the delivery of full chemotherapy doses on schedule.

Keywords: anaemia; gastric cancer; leukopenia; neutropenia; thrombocytopenia.