Second-line chemotherapy for gastric cancer: a new issue lies ahead in global trials

Abstract

Chemotherapy for gastric cancer has been advancing fairly well. It has been indicated that not only advances in first-line chemotherapy but also those in second-line chemotherapy have contributed to the prolongation of overall survival. The Arbeitsgemeinschaft Internistische Onkologie (AIO) study supports the idea that second-line chemotherapy is appropriate in patients with a good general condition. Also, the Japan Clinical Oncology Group (JCOG) integral analysis suggests that advances have been made in second-line chemotherapy. However, most recently reported studies of second-line chemotherapy have been conducted as small-scale phase II or retrospective trials. No randomized control trial to establish standard treatment has been reported. Which regimen is the most appropriate as second-line therapy must be investigated in the future. Currently, molecularly targeted agents for gastric cancer are being developed and tested in global trials. As a new issue in global trials, second-line chemotherapy has been emphasized. In recent global trials, subset analysis showed regional differences in overall survival. This was possibly associated with the regional differences in second-line chemotherapy. When developing new molecularly targeted agents for first-line chemotherapy, we cannot ignore the result that the proportion of patients in whom treatment was switched to second-line chemotherapy was high in Asia. In planning a global trial, this new issue should be sufficiently discussed.

Taxanes in the Treatment of Advanced Gastric Cancer

“…In particular, paclitaxel, docetaxel, and irinotecan have been identified promising drugs whether in combination regimens or as single agents. According to the results of several recent studies, the patient response rates ranged from approximately 10% to 20%, and the PFS ranged from 2.5 to 4.0 months [14]. Interestingly, the survival period following the failure of first-line chemotherapy has been shown to be longer in Asia than in Western countries, possibly due to the higher proportion of patients who receive subsequent chemotherapy in Asia and differences in the patient characteristics [15].…”

Pemetrexed for previously treated patients with metastatic gastric cancer: a prospective phase II study

“…Chemotherapy with less toxicity, better disease control and life prolongation should be considered preferentially. Some phase II trials showed that combination chemotherapy achieved no marked survival benefits in the second-line setting ( Takiuchi, 2011 ; Kang et al , 2012 ). Therefore, we chose not combination but single agent for the second-line treatment.…”

A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy

“…Although multiple drugs have been evaluated as second-line therapy in phase II trials and retrospective cohorts, there have been no randomized head-to-head trials designed to establish a standard treatment in this setting [43]. Comparisons of second-line therapy across clinical studies are problematic for multiple reasons, including the nature of previous chemotherapy and responses to first-line chemotherapy [13].…”

“…This is particularly important in advanced gastric cancer since response duration to first-line chemotherapy is prognostic for the benefit of second-line chemotherapy [44, 45]. With targeted agents being increasingly tested in conjunction with first-line chemotherapy, it will be important to evaluate how they impact the activity of subsequent second-line treatment and, conversely, how second-line therapy affects outcomes measured with first-line regimens [43]. …”