Efficacy and Toxicity of Low-Dose versus Conventional-Dose Chemotherapy for Malignant Tumors: a Meta-Analysis of 6 Randomized Controlled Trials

低剂量与常规剂量化疗治疗恶性肿瘤的疗效和毒性:6项随机对照试验的荟萃分析

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Abstract

Low-dose chemotherapy has emerged as a new strategy for control of cancer. However, there is a controversy as to whether low-dose chemotherapy is an effective way to manage many human malignancies. To shed light on this controversy, we performed a meta-analysis of relative merits between low-dose and conventional-dose chemotherapy in different carcinomas. Studies published before February 29, 2016 were reviewed for the meta-analysis and selected according to defined criteria. The effect levels of low-dose chemotherapy regarding overall survival (OS), progression-free survival (PFS) and severe adverse events (SAEs) (Grade≥3) were calculated as risk ratios (ORs) or adjusted hazard ratios (HRs). Six randomized controlled studies (RCTs) have provided data for low-dose chemotherapy versus conventional-dose chemotherapy for 838 cases and 833 cases, respectively. Interestingly, low-dose chemotherapy achieved the same desired potency as conventional-dose chemotherapy, with no differences in pooled ORR (RR=1.00, 95%CI [0.89, 1.13]; (P=0.97), OS (HR=1.07, 95%CI [0.90, 1.26]; P=0.44) and PFS (HR=1.02, 95%CI [0.84, 1.23]; P=0.87) values. Furthermore, pooled data for common SAEs showed that, compared with conventional-dose chemotherapy regimen, low-dose chemotherapy regimen resulted in significant less mucositis (P<0.0001), thrombocytopenia (P<0.00001), anemia (P=0.0001) and febrile neutropenia (P=0.004). At the same time, no statistically significant differences were observed with regard to treatment-related death (P=0.36), diarrhea (P=0.49), leucopenia (P=0.11), neutropenia (P=0.74) and nausea/vomiting (ʺPʺ=0.21). Publication bias was assessed by Egger’s test and the funnel plot. In conclusion, the meta-analysis seems to support the idea that low-dose chemotherapy may play an important role in achieving the same desired potency as conventional-dose chemotherapy in managing malignant tumors. Moreover, low-dose regimen seems to possess positive advantages of lower toxicity which is a particular concern for most patients.

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