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

Abstract

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.

Keywords: Metastatic colorectal cancer; advanced colorectal cancer; pemetrexed; third-line treatment.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-1095). The authors have no conflicts of interest to declare.

2020 Annals of Translational Medicine. All rights reserved.

Figures

Figure 1

Kaplan-Meier curves depicting survival in patients with different treatment combinations. (A) Kaplan-Meier curve for progression-free survival; (B) Kaplan-Meier curve for overall survival. PFS, progression-free survival; OS, overall survival.

Figure 2

The changing rate of CEA during treatment of CEA-positive (>4.71 ng/mL) patients in the two groups. (A) All positive patients, (B) patients excluding progression within 2 months. CEA, carcinoembryonic antigen.

Figure 3

Changing rate of target lesions of patients in the two groups. Changing rate was evaluated when the curative effect or progression appeared.

Figure 4

Time distribution of treatment initiation in two groups. The time distribution of treatment initiation in the two groups differed, and the superior treatment group was closer overall.