title: Etoposide added to weekly leucovorin (LV)/5-fluorouracil (5-FU) in LV/5-FU pre-treated patients with advanced colorectal cancer.
abstract: BACKGROUND
  We evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV + 5-FU.
  
  
  METHODS
  Etoposide was administered at 3 different dose levels (DL), in 3 groups of patients (total=60): DL-I - etoposide 80 mg/m2, 45 min i.v. infusion, DL-II - etoposide 120 mg/m2, and DL-III - etoposide 180 mg/m2. In all three levels etoposide was followed by LV 100 mg/m2 i.v., 1-hour infusion, and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered until disease progression or unacceptable toxicity.
  
  
  RESULTS
  No patients responded at DL-I, while 2 patients at DL-II and 3 at DL-III had a partial response (PR) (P<0.1). Two patients had stable disease (SD) at DL-I, 8 at DL-II, and 9 at DL-III (P<0.01). More patients progressed at DL-I (n=19) compared to DL-II (n=10) and DL-III (n=8) (p<0.0007). The time to progression was 17, 15, and 14 weeks, respectively, for DL-I, -II, and -III (P=0.9). Median survival was 30, 30, and 32.5 weeks, respectively, for DL-I, -II, and -III (P= 0.27). Toxicity was mainly neutropenia, diarrhea and mucositis at all DLs, significantly more intense in DL-III. No difference was noticed in responses between DL-II and DL-III, but toxicity in DL-III was more severe.
  
  
  CONCLUSIONS
  The combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC.
authors.affiliation: Department of Pathophysiology, Medical Oncology Unit, University of Athens, School of Medicine, Laikon General Hospital, Greece.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsavaris
authors.forename: Christos
authors.initials: C
authors.lastname: Kosmas
authors.forename: Kostas
authors.initials: K
authors.lastname: Gennatas
authors.forename: Maria
authors.initials: M
authors.lastname: Vadiaka
authors.forename: Platon
authors.initials: P
authors.lastname: Paliaros
authors.forename: Antonis
authors.initials: A
authors.lastname: Dimitrakopoulos
authors.forename: Theodoros
authors.initials: T
authors.lastname: Diamantis
authors.forename: Heraklis
authors.initials: H
authors.lastname: Tsipras
authors.forename: George
authors.initials: G
authors.lastname: Papastratis
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005047:Etoposide / Q000008:administration & dosage*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D002955:Leucovorin; D005472:Fluorouracil