A Four-Arm, Randomized, Multicenter Phase II Trial of Oxaliplatin Combined with Varying Schedules of 5-Fluorouracil as First-line Therapy in Previously Untreated Advanced Colorectal Cancer

Efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer: a systematic review and meta‐analysis

“…The pooled RR of 0.35 (95% CI, 0.18–0.66; P = 0.000) for mucositis, in the five trials, showed that mucositis was more frequent in the conventional chemotherapy group. As an obvious heterogeneity ( P = 0.000; I 2 = 92.7%) existed, in the five trials, for mucositis, a sensitivity analysis was applied to explore the factors contributing to heterogeneity.…”

“…A total of 835 articles were identified from the electronic search, of which five trials met all inclusion criteria. One additional trial was found through a reference check, ultimately, resulting in six trials for our meta‐analysis . Quality assessment resulted in four trials scoring two points, one trial scoring three points and one trial scoring one point.…”

“…Five articles reported the incidence of vomiting and nausea in the chrono‐chemotherapy and conventional chemotherapy groups. The combined RR of 1.02 (95% CI, 0.78–1.35; P = 0.872) indicated no significant difference in terms of vomiting and nausea, and there was no heterogeneity ( P = 0.212; I 2 = 31.4%) confirmed in the five articles.…”

“…All trials testing diarrhea pointed that there was a high frequency of diarrhea in the chrono‐chemotherapy group compared to the conventional chemotherapy group with a pooled RR of 1.60 (95% CI, 1.30–1.97; P = 0.000), but an obvious heterogeneity ( P = 0.000; I 2 = 79.7%) existed in these trials. A random‐effect model was employed to calculate the combined RR (RR = 1.44; 95% CI, 0.87–2.36; P = 0.149), which indicated there was no significant difference between two groups.…”

“…As the four trials testing neutropenia did not show heterogeneity ( P = 0.235, I 2 = 44.6%), a fixed‐effect model was employed to give a combined RR of 0.40 (95% CI, 0.27–0.57; P = 0.000), indicating that neutropenia was more frequent in patients treated with conventional chemotherapy.…”