Analysis of pemetrexed-based chemotherapy in the treatment of advanced colorectal cancer

BACKGROUND: In this study, we evaluated the therapeutic efficacy and toxicity profile of chemotherapy combinations containing pemetrexed for patients with metastatic colorectal cancer. We investigated the optimal chemotherapy treatment regimen to provide a new option for third-line or after treatment of patients with advanced colorectal cancer. METHODS: A total of 88 eligible patients with metastatic colorectal cancer were included in this study from April 2009 to March 2019 at the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University. The baseline information and treatment outcomes of the patients were collected. Statistical analyses of different chemotherapy regimens focusing on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity were conducted. The superior treatment regimen was determined, and its clinical outcomes were compared with those of the other treatment combinations to explore the factors that potentially contributed to the curative effect. RESULTS: The 88 patients in this study received 18 treatment regimens. In total, 53 patients had progressive disease (PD), 34 patients had stable disease (SD), 1 patient was assessed as complete response (CR), and no patients had a partial response (PR). The optimal regimen was pemetrexed + S-1 + bevacizumab. The 21 patients treated with this regimen exhibited a higher DCR [61.90% vs. 32.84%, odds ratio (OR) =3.324; 95% confidence interval (CI): 1.201–9.196, P=0.018] than patients treated with the other chemotherapy regimens. Moreover, the median PFS of this regimen was 4.57 (2.62–6.51) months, which was significantly longer [hazard ratio (HR) =0.566; 95% CI: 0.330–0.971, P=0.039] than the 2.57 (2.18–2.95) months of the other regimens. In terms of toxicity, leukopenia (34.1%) and neutropenia (34.1%) had the highest incidence of all-grade adverse events (AEs). Grade 3–4 AEs included neutropenia (15.9%), leukopenia (11.4%), thrombocytopenia (2.3%), and anemia (1.1%). CONCLUSIONS: The combination of pemetrexed + S-1 + bevacizumab was found to be the optimal treatment regimen. This combination was superior to the other treatment regimens in terms of DCR and PFS with controllable toxicity. These results warrant further prospective exploratory clinical trials for pemetrexed-based chemotherapy in metastatic colorectal cancer.