title: Leucovorin and fluorouracil vs levamisole and fluorouracil as adjuvant chemotherapy in rectal cancer.
abstract: The aim of this study was to evaluate the effectiveness of 6-month therapy with leucovorin (LV) + 5-fluorouracil (5-FU) vs 12 months of therapy with levamisole (LVZ) + 5-FU, as adjuvant chemotherapy in patients with completely resected Dukes' stage B2 or C rectal cancer. One hundred and fifty patients with surgically resected rectal carcinoma, were enrolled in the present study; Dukes' stage B2 (n=70) or C (n=80), were randomly assigned to chemotherapy with 5-FU + LV x 6 months or 5-FU + LVZ x 12 months. Patient characteristics were equally balanced between the examined groups. Adjuvant CT consisted of LV 20 mg/m(2) intravenously (i.v.) plus 5-FU 450 mg/m(2) i.v., on days 1-5 every 4 weeks for 6 cycles or 5-FU 450 mg/m(2) i.v. every week plus LVZ 50 mg t.i.d x 3 days for 1 year. All patients received radiotherapy with a three-field technique to a total dose of 45 Gy, over 5 weeks. After a median follow-up of 7.4 years there were no significant differences between the two treatment groups with respect to the recurrence rates (P=0.821). Moreover, there was no difference in disease-free survival for patients stage Dukes' B2 (log-rank p=0.73); median for LV group 90 (8-131) months, and for LVZ group 86.5 (3-129) months. No difference was noted in disease-free survival for patients stage Dukes' C (log-rank p=0.73); median for LV group 60 (17-128) months, and for LVZ group 64 (2-123) months. There was no difference in overall survival for patients stage Dukes' B2 (log-rank p=0.75); median for LV group 90 (22-131) months, and for LVZ group 86 (10-129) months. For stage Dukes' C (log-rank p=0.73); median for LV group 67 (17-128) months, and for LVZ group 64 (5-123) months. Toxicities were as follows in the 5-FU + LVZ vs 5-FU + LV group; myelosuppression (leucopenia grade 3, 12% vs 4%, p<0.04), diarrhea (grade 0, 60% vs 76%, p<0.02), and liver toxicity (increase of transaminases >3-fold, 12 patients vs 2, p<0.03), were more frequent in LVZ group. None of the patients stopped chemotherapy because of the toxicity, and there were no toxicity-related deaths. In conclusion, adjuvant chemotherapy in RC with LV + 5-FU for 6 months is equally effective and less toxic than LVZ + 5-FU for 12 months.
authors.affiliation: Department of Pathophysiology, University of Athens, School of Medicine, 'Laikon' General Hospital, Athens 11527, Greece. tsavari1@otenet.gr
authors.forename: N
authors.initials: N
authors.lastname: Tsavaris
authors.forename: K
authors.initials: K
authors.lastname: Gennatas
authors.forename: C
authors.initials: C
authors.lastname: Kosmas
authors.forename: H M
authors.initials: HM
authors.lastname: Skopelitis
authors.forename: P
authors.initials: P
authors.lastname: Gouveris
authors.forename: A
authors.initials: A
authors.lastname: Dimitrakopoulos
authors.forename: M
authors.initials: M
authors.lastname: Zacharakis
authors.forename: G
authors.initials: G
authors.lastname: Kouraklis
authors.forename: J
authors.initials: J
authors.lastname: Vasiliou
authors.forename: E
authors.initials: E
authors.lastname: Felekouras
authors.forename: D
authors.initials: D
authors.lastname: Voros
authors.forename: G
authors.initials: G
authors.lastname: Zografos
authors.forename: M
authors.initials: M
authors.lastname: Balafouta
authors.forename: M
authors.initials: M
authors.lastname: Paraskevaidis
authors.forename: M
authors.initials: M
authors.lastname: Safioleas
authors.forename: K
authors.initials: K
authors.lastname: Fotiadis
authors.forename: G
authors.initials: G
authors.lastname: Papastratis
authors.forename: G
authors.initials: G
authors.lastname: Karatzas
authors.forename: E
authors.initials: E
authors.lastname: Papalambros
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil