A Randomized Trial Comparing Cisplatin Plus 5-fluorouracil With or Without Levamisole in Operable Gastric Cancer

Abstract

ObjectivesTo determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer.MethodsAfter en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000mg/m2/day administered as continous infusion for 5 days, cisplatin 60mg/m2/day as intravenous infusion for 1 day with or without levamisole (50mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable.ResultsThe fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p=0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. Howerer. this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2–3 toxicites were nausea/vomiting (levamisole, non-levamisole group;31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%).ConclusionLevamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.

Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis

“…Finally, 97 references were identified on 72 original RCTs. In total, 39 studies reported data on prognostic and/or predictive factors for gastric cancer [3,4,5,6,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53] and 33 studies on esophageal cancer [8,10,11,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,…”

“…Prognostic factors for the curative treatment of gastric cancer identified from overall survival (OS) multivariate analyses in at least one randomized control trial (RCT). In total, there were 32 RCTs contributing to Figure 2 with 27 investigating adjuvant therapy [4,5,6,19,20,21,22,23,24,25,26,27,29,30,31,32,34,35,36,37,39,40,41,42,43,45,49,52,53] and five investigating neoadjuvant therapy [3,28,33,38,51]. The Mandard score was only assessed in patients who received preoperative chemotherapy according to the MAGIC regimen [93].…”

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

“…However, the lack of a comparison group without levamisole precludes definitive conclusions to be drawn about the effect of immunotherapy in our study. On the other hand, in some studies it has been reported that adding levamisole to combination chemotherapy offered no improvement or even had a negative effect on treatment outcome [5,6,20]. In the study by Choi et al [6], 100 patients with operable gastric cancer were randomized to 5-FU, cisplatin and levamisole and to chemotherapy-only arms after gastric resection.…”

“…On the other hand, in some studies it has been reported that adding levamisole to combination chemotherapy offered no improvement or even had a negative effect on treatment outcome [5,6,20]. In the study by Choi et al [6], 100 patients with operable gastric cancer were randomized to 5-FU, cisplatin and levamisole and to chemotherapy-only arms after gastric resection. At a median follow-up of 39 months, the levamisole group tended to show more risk in terms of overall death rate and recurrence than the nonlevamisole group, although this result was not statistically significant at 3 years (p = 0.284).…”