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

Abstract

<br /> <span style="font-size: small;">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 </span><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">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]; (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.97), OS (HR=1.07, 95%CI [0.90, 1.26]; </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.44) and PFS (HR=1.02, 95%CI [0.84, 1.23]; </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.87) values. </span></span><span style="font-size: small;">Furthermore, pooled data for common SAEs showed that, compared with conventional-dose chemotherapy regimen, </span><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">low-dose chemotherapy regimen resulted in significant less mucositis (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-size: small;"><0.0001), thrombocytopenia (</span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-size: small;"><0.00001), anemia (</span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.0001) and febrile neutropenia (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.004). At the same time, no statistically significant differences were </span></span><span style="font-size: small;">observed with regard to treatment-related death (</span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.36), diarrhea (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.49), leucopenia (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.11), neutropenia (</span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P</span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN"><span style="font-family: Times New Roman,Times New Roman; font-size: small;" lang="ZH-CN">=0.74) and nausea/vomiting (ʺʺ0.21). Publication bias was assessed by Egger?s test and the funnel plot. In conclusion, the </span></span><span style="font-size: small;">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. </span>