Improved Chemotherapy for Gastric Cancer?
December 1, 1997
ABSTRACT & COMMENTARY
Chemotherapy for gastric cancer has improved little since the original reports of the efficacy of the FAM regimen (5-fluorouracil, doxorubicin, and mitomycin C). Later reports have led to doubt about whether FAM was better than single-agent 5-fluorouracil. Thus, it could be argued that no progress has occurred at all. Claims of superiority accompanied the introduction of FAMTX (5-fluorouracil, doxorubicin, and methotrexate), EAP (etoposide, doxorubicin, and cisplatin), and ELF (etoposide, leucovorin, and 5-fluorouracil); however, these regimens were found to be either too toxic or no more effective than other, less aggressive regimens. One randomized trial has shown that prolonged (6 months) infusion of 5-fluorouracil with cisplatin and epirubicin (ECF) was superior to FAMTX.1 However, a recent report from Italy suggests that an intense, multi-agent regimen induces tumor regression in the majority of patients and that a significant fraction achieve complete remissions.
The Italian Group for the Study of Digestive Tract Cancer took what they felt were the most active agents in gastric cancer (5-fluorouracil, cisplatin, and an anthracycline), added leucovorin to enhance 5-fluorouracil efficacy, administered therapy weekly to increase dose intensity, and added glutathione and G-CSF to reduce neurotoxicity and hematopoietic toxicity, respectively. Cisplatin 40 mg/m2, 5-fluorouracil 500 mg/m2, epidoxorubicin 35 mg/m2, and leucovorin 250 mg/m2 were given IV weekly for eight weeks. Patients received an additional six weeks of therapy if they were responding or had stable disease. G-CSF 5 mcg/kg was given daily for six days after each weekly treatment. This regimen had shown significant promise when used in a single institution.2
One hundred five patients with locally advanced and/or metastatic gastric cancer were treated between 1993 and 1995. Tumor regression was observed in 65 of 105 patients; the overall response rate was 62% (53-71%; 95% confidence interval). The complete response rate was 17%, and the partial response rate was 45%. Tumor regression was observed at similar rates regardless of the site of disease; liver, lung, lymph node, and peritoneal sites responded. The median survival time was 11 months, with two-year survival of 5%. Although morbidity, particularly myelosuppression, was significant, treatment-related deaths were not observed. Data on the rate of hospitalization were not reported. (Cascinu S, et al. J Clin Oncol 1997;15:3313-3319.)
COMMENTARY
This study confirms the high response rate observed using the same regimen in a single institution study.2 The results compare favorably with the ECF regimen, which had a 41% response rate, an approximate nine-month median survival, and was found to be superior to FAMTX in a randomized trial.1 The new Italian regimen is given in the outpatient clinic, but we are not given information about the need for hospitalization, its impact on quality of life, or its costs in financial terms. Any regimen that induces complete responses in advanced solid tumors is worthy of further study. Not only did this regimen induce complete responses, it also induced sufficient reduction in the size of tumor masses to make some of them surgically resectable. Its examination in a prospective randomized trial would be important. If 5% of patients are actually cured with this treatment program, it would represent a significant advance. This regimen should also be studied in the adjuvant and neoadjuvant settings where it seems likely to have significant effects on survival.
References
1. Webb A, et al. J Clin Oncol 1997;15:261-267.
2. Cascinu S, et al. Int J Oncol 1993;3:535-538.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content