Pemetrexed Monotherapy as Salvage Treatment in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy: A Phase II Single-arm Prospective Trial

Sung Won Lim, Sujin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim, Sung Won Lim, Sujin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim

Abstract

Background: We designed a single-arm, open-label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplementation in patients with refractory colorectal cancer (CRC) that failed to respond to standard treatments including 5-fluorouracil, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1 every 3 weeks, with folic acid and vitamin B12 supplementation. Treatment was continued until disease progression or intolerable toxicity. Between June 2016 and October 2016, 24 patients were enrolled in this study. Results: One patient withdrew consent, leaving a total of 23 patients for evaluation. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). There was no patient with complete response (CR) or partial response (PR). However, stable disease was observed in 10 patients (43.4%) and maintained more than 6 months in 7 of 10 patients. The median progression-free survival was 1.6 months (95% CI, 1.1-2.0) and the median overall survival was 9.8 months (95% CI, 5.9-13.6). Grade 3 treatment-related adverse events occurred in one patient with elevated liver enzymes and hematologic adverse event of grade 2 anemia was observed in one patient. There were no cases of dose reduction or treatment-related deaths and all toxicities were manageable. Conclusions: Pemetrexed monotherapy showed moderate disease control and acceptable toxicity profile as salvage therapy for refractory CRC.

Keywords: Pemetrexed; colorectal cancer; vitamin.

Conflict of interest statement

Competing Interests: Pemetrexed was kindly provided by Dong-A for this study. Clinical research grants were supported by Dong-A (S.T. Kim). The other authors have no potential conflicts of interest to declare.

Figures

Figure 1
Figure 1
Number of cycles of pemetrexed administration for all patients. 7 patients received six or more cycles, and two of them have still been received pemetrexed at time of writing. The arrow indicates that treatment is ongoing.
Figure 2
Figure 2
Kaplan-Meier curves of progression-free survival (PFS) from first pemetrexed dose. The median PFS was 1.6 months.
Figure 3
Figure 3
Kaplan-Meier curves of overall survival (OS) from first pemetrexed dose. The median OS was 9.8 months.

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