Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study

Background: Esophageal squamous cell cancer (ESCC) accounts for approximately 90% of esophageal cancer cases in China. There are no standard regimens for second or third-line chemotherapy of metastatic squamous esophageal cancer. The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC.

Methods: One hundred and twenty-eight patients with metastatic ESCC confirmed by histopathology were enrolled into this study. These patients had failure of the first-line chemotherapy combination of fluorouracil or platinum or paclitaxel and had not undergone chemotherapy with irinotecan or raltitrexed previously. Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group). Overall survival (OS) and progression-free survival (PFS) were the primary endpoint.

Results: In the control group, the median PFS (mPFS) and median OS (mOS) of patients were 3.37 and 5.3 months. In the experiment group, mPFS and mOS were 3.91 and 7.0 months. There was statistical significance of PFS and OS between two groups (PFS P = 0.002, OS P = 0.01). In subgroup analysis, in the second-line treatment, the mPFS of control and experiment group, was 3.90 and 4.60 months, mOS was 6.95 and 8.5 months, which was statistically significant differences between the two groups. (PFS P = 0.001, OS P = 0.005), In the third-line and beyond treatment, mPFS of control and experiment group was 2.80 and 3.19 months, mOS were 4.5 and 4.8 months. But there was no significant difference of PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31). There was no statistical significance of toxicity side effects between two groups.

Conclusions: The PFS and OS of irinotecan plus raltitrexed may be better than that of irinotecan monotherapy, especially in second line treatment, which should be confirmed with a phase III study including much more patients.

 

Comments:

This study aimed to investigate the safety and effectiveness of two different salvage chemotherapy regimens for metastatic esophageal squamous cell cancer (ESCC). The study included 128 patients who had previously received first-line chemotherapy but experienced treatment failure with fluorouracil, platinum, or paclitaxel. None of the patients had undergone chemotherapy with irinotecan or raltitrexed previously.

The patients were randomly divided into two groups: the irinotecan combined with raltitrexed group (experiment group) and the irinotecan monotherapy group (control group). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS).

The results showed that the median PFS (mPFS) and median OS (mOS) in the control group (irinotecan monotherapy) were 3.37 and 5.3 months, respectively. In the experiment group (irinotecan combined with raltitrexed), the mPFS and mOS were 3.91 and 7.0 months, respectively. The study found statistical significance in PFS (P = 0.002) and OS (P = 0.01) between the two groups, indicating that the combination therapy had better survival outcomes compared to monotherapy.

In the subgroup analysis, when focusing on the second-line treatment, the mPFS and mOS were significantly better in the experiment group (4.60 and 8.5 months) compared to the control group (3.90 and 6.95 months) (PFS P = 0.001, OS P = 0.005). However, in the third-line and beyond treatment, there was no significant difference in PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31).

Importantly, the study did not find any statistical significance in toxicity side effects between the two groups, indicating that the combination therapy did not result in significantly increased adverse effects.

In conclusion, the study suggests that the combination of irinotecan and raltitrexed may be more effective than irinotecan monotherapy, particularly in the second-line treatment of metastatic ESCC. However, the findings need to be confirmed with a larger phase III study to further validate the results.

Related Products

Cat.No.	Product Name	Information
S1192	Raltitrexed	Raltitrexed (ZD-1694) is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth.

Related Targets

DNA/RNA Synthesis Thymidylate Synthase