Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

作者：Xiaoying Zhao; Zhiyu Chen; Xiaowei Zhang; Xiaodong Zhu; Wen Zhang; Lixin Qiu; Chenchen Wang; Mingzhu Huang; Zhe Zhang; Wenhua Li; Lei Yang; Weijian Guo^*

来源：Cancer Biology & Medicine, 2023, 20(09): 682-688.

Objective: Paclitaxel(P) is a standard second-line chemotherapy in the treatment of advanced gastric cancer. This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP) regimen as second-line treatment in metastatic gastric cancer(MGC) patients.Methods: An open, randomized, multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP [raltitrexed(3 mg/m2 on day 1) and paclitaxel(135 mg/m2 on day 1 every 3 weeks)] or P [paclitaxel(135 mg/m2 on day 1 every 3 weeks)] as 2nd-line chemotherapy. The primary endpoint was progression-free survival(PFS). The secondary endpoints were the overall response rate(ORR), overall survival(OS), and safety.Results: PFS had a tendency to be prolonged with RP compared to P(2.7 months vs. 1.7 months; P = 0.148). OS was also prolonged with RP compared to P(10.2 months vs. 6.1 months; P = 0.140). The ORR was equal in the RP and P groups(6.8% and 4.0%; P = 0.72). The disease control rate(DCR) in the RP and P groups was 56.2% and 36.0%, respectively. Grade 3-4 treatment-related adverse events occurred in 36.2%(RP) and 28.2%(P) of patients. Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0% and 4.0%), anemia(1.4% and 4.0%), and thrombocytopenia(1.4% and 5.3%), and all grades of peripheral neurotoxicity(12.3% vs. 17.3%). All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4% and 14.1%). Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement, the OS of the RP regimen was longer(P = 0.05).Conclusions: Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS, especially among patients with ascites or peritoneal involvement, which warrants confirmation using larger sample studies.

• 单位
  复旦大学; 南通市肿瘤医院