Abstract
Chemotherapy-induced neutropenia (CIN) reportedly indicated better prognosis for some cancers. We retrospectively analyzed 150 evaluable metastatic gastric cancer (MGC) patients who had received first-line EOF5 (combination regimen of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil) treatment. We divided patients into three groups according to the worst grade of CIN: absent group (grade 0), moderate group (grade 1-2) and severe group (grade 3-4). Multivariate analyses of overall survival (OS) proved moderate and severe CIN were important prognostic factors whether regarding CIN as a time-varying covariate (TVC) or not. Compared with absent CIN, hazard ratio (HR) for moderate and severe CIN were 0.31 (95% confidential interval (CI): 0.17-0.55; P < 0.001) and 0.36 (95% CI: 0.20-0.64; P = 0.001) respectively with TVC; and were 0.31 (95% CI: 0.17-0.56; P < 0.001) and 0.34 (95% CI: 0.19-0.61; P < 0.001) respectively without TVC. In progression-free survival (PFS) analyses, moderate and severe CIN showed similar results. In the landmark group (n = 122 patients) analyses with TVC, moderate and severe CIN remained prognostic factors for PFS, while only moderate CIN was prognostic factor for OS. CIN predicted longer OS and PFS in MGC patients treated with first-line EOF5 chemotherapy.
Highlights
Gastric cancer is the fourth most common malig nancy and the second most common cause of cancerrelated death worldwide [1], and currently no standard first-line treatment regimen for gastric cancer is in place
Of the 120 patients who developed chemotherapy-induced neutropenia (CIN), the highest grade of CIN occurred during the first cycle in 28 patients, the second cycle in 32 patients, the third cycle in 21 patients, the fourth cycle in 19 patients, the fifth cycle in 9 patients and the sixth cycle in 11 patients; 83% went through their severest CIN within 4 cycles
The median number of cycles of Combination regimen of epirubicin (EOF5) administrated in the absent neutropenia group (4, range 1–7) was lower than that in the moderate group (6, range 2–8) or severe group (6, range 2–8), but the relative dose-intensity (RDI) was higher in the absent group
Summary
Gastric cancer is the fourth most common malig nancy and the second most common cause of cancerrelated death worldwide [1], and currently no standard first-line treatment regimen for gastric cancer is in place. Fluoropyrimidine and platinum-based dual or triplet therapies have been the most widely used regimens for metastatic gastric cancer (MGC). The combination of epirubicin, cisplatin and 5-fluorouracil (ECF) and its modifications have shown efficacy and manageable toxicity [2], but only about 50% patients respond to it [3]. Identification of factors that predict efficacy in order to improve clinical outcome is necessary. Patients have been receiving body surface area (BSA)-based standard dosages, which were established by small-scale dose-finding trials. Standard dosages may be too small for optimal efficacy in some patients, or too large to avoid unnecessary adverse effects in others [10]. Bergh J et al’s study strongly supported individualized toxicity tailored chemotherapy, www.impactjournals.com/oncotarget with a superior clinical outcome to routine chemotherapy in that study [11]
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