COMBINED INTRAPERITONEAL PLUS INTRAVENOUS CHEMOTHERAPY AFTER CURATIVERESECTION FOR COLONIC ADENOCARCINOMA

Patients who underwent potential curative surgery for colonic adenocar cinoma were enrolled in a prospectively randomised, controlled clinica l trial of combined intraperitoneal (i.p.) plus systemic intravenous ( i.v.) chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant treatment approach, specifically ad dressing the risk of peritoneal and hepatic recurrence, could improve disease-free and overall survival. Between May 1988 and December 1990, 121 patients with resected stage III or high-risk stage II (T4NOMO) c olon cancer were randomly assigned for observation (which was consider ed standard care until the NM consensus conference) or adjuvant chemot herapy with LV (200 mg/m(2)) plus 5-FU (350 mg/m(2)), both given i.v. (days 1-4) and i.p. (days 1 and 3) every 4 weeks for a total of six co urses. After a median follow-up time of 4.6 years, a comparative analy sis between the two groups of patients suggested both an improvement i n disease-free survival (75% versus 58%; P = 0.06) and a survival adva ntage (78% versus 63%; P = 0.05) in favour of adjuvant chemotherapy. T he sites of recurrence were also different, i.e. local regional and in trahepatic tumour recurrences were observed in only 6/58 (10%) and 5/5 8 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%) observed patients. The overall benefit of adjuvant therapy appea red to be greatest in patients with stage III colon cancer. Treatment- associated toxicity was infrequent and generally mild with only 5% exp eriencing severe (WHO grade 3) adverse reactions. Interim results of t his adjuvant trial suggest that combined i.p. plus systemic i.v. chemo therapy with 5-FU and LV represents a potentially effective adjuvant r egimen in stage II/III colon cancer.