Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial.

OBJECTIVE: To evaluate the results of a prospective multicenter randomized study of adjuvant intraperitoneal 5-fluorouracil (5-FU) administered during 6 days shortly after resection of stages II and III colon cancers. SUMMARY BACKGROUND DATA: Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months. Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects. METHODS: After resection, 267 patients were randomized into two groups. Patients in group 1 (n = 133) underwent resection followed by intraperitoneal administration of 5-FU (0.6 g/m2/day) for 6 days (day 4 to day 10). These patients also received intravenous 5-FU (1 g) during surgery. Patients in group 2 underwent resection alone (n = 134). RESULTS: In group 1, 103 patients received the total dose, 18 received a partial dose as a result of technical or tolerance problems, and 12 did not receive the chemotherapy. Rates of surgical death and complications were similar in both groups. Tolerance to treatment was excellent or fair in 97% of the patients and poor in 3%. After a median follow-up of 58 months, 5-year overall survival rates were 74% in group 1 and 69% in group 2; disease-free survival rates were 68% and 62%, respectively. Survival curves were superimposed until 3 years after treatment and began diverging thereafter. Among patients receiving the full treatment, the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers. CONCLUSIONS: Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly. However, it reduced the risk of recurrence in stage II cancers. These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences.

Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity 320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.

[Colovesical fistula of diverticular origin. Diagnostic and therapeutic aspects. 17 cases]. / Fistules colo-vésicales d'origine diverticulaire. Aspects diagnostiques et thérapeutiques. Dix-sept observations.

Seventeen patients presenting with diverticular colovesical fistula were treated surgically between 1975 and 1979. Any treatment of the fistula must aim at the cause--colonic diverticulitis--by resection of the colon and colorectal anastomosis. Colostomy was performed in two cases. The bladder was closed by simple suture and a urethral catheter was left in place for ten days. There were few complications, though one patient died. Pneumaturia and fecaluria are specific symptoms. Intravenous pyelography and cystoscopy are of little assistance and only a barium enema should be performed for preoperative diagnosis.