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

Cancer Biol Med. 2023 Aug 31;20(9):682-688. doi: 10.20892/j.issn.2095-3941.2023.0112.

Abstract

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.

Keywords: Gastric adenocarcinoma; paclitaxel; raltitrexed; second-line palliative chemotherapy.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Ascites / chemically induced
  • Ascites / drug therapy
  • Humans
  • Paclitaxel
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology

Substances

  • Paclitaxel
  • raltitrexed