Second-Line Chemotherapy vs Supportive Care in Gastric Cancer
Background: Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.
Patients and methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.
Results: The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.
A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001] was observed with salvage chemotherapy.
When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.
Conclusion: This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.
Gastric cancer is the fourth most frequent malignant disease and the second most common cause of cancer-related death in the world; it is also the second most frequent malignancy in Korea. Although patients with early gastric cancer can be cured by surgical resection with perioperative or adjuvant chemotherapy, a large majority of patients experience a relapse after initial surgery or are diagnosed with unresectable, locally advanced or metastatic disease. Systemic chemotherapy with combination of fluoropyrimidine and platinum is now regarded as the standard treatment of these patients. However, the efficacy of first-line treatment is modest, and most patients are nonresponders or eventually experience disease progression.
Even though patients with refractory gastric cancer have received salvage chemotherapy in routine clinical practice, especially in Asia, there was no evidence to support salvage chemotherapy until recent phase III trials demonstrated substantial prolongation of overall survival. Results of three randomized, controlled trials (RCT) were published as articles or abstract and showed overall survival benefit from treatments with irinotecan or docetaxel compared with best supportive care (BSC) alone in patients for whom one or two prior treatments failed. We conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than BSC.
Abstract and Introduction
Abstract
Background: Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.
Patients and methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.
Results: The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.
A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001] was observed with salvage chemotherapy.
When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.
Conclusion: This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.
Introduction
Gastric cancer is the fourth most frequent malignant disease and the second most common cause of cancer-related death in the world; it is also the second most frequent malignancy in Korea. Although patients with early gastric cancer can be cured by surgical resection with perioperative or adjuvant chemotherapy, a large majority of patients experience a relapse after initial surgery or are diagnosed with unresectable, locally advanced or metastatic disease. Systemic chemotherapy with combination of fluoropyrimidine and platinum is now regarded as the standard treatment of these patients. However, the efficacy of first-line treatment is modest, and most patients are nonresponders or eventually experience disease progression.
Even though patients with refractory gastric cancer have received salvage chemotherapy in routine clinical practice, especially in Asia, there was no evidence to support salvage chemotherapy until recent phase III trials demonstrated substantial prolongation of overall survival. Results of three randomized, controlled trials (RCT) were published as articles or abstract and showed overall survival benefit from treatments with irinotecan or docetaxel compared with best supportive care (BSC) alone in patients for whom one or two prior treatments failed. We conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than BSC.