title: Safety and efficacy of outpatient treatment with CPT-11 plus bolus folinic acid/5-fluorouracil as first-line chemotherapy for metastatic colorectal cancer.
abstract: The combination of irinotecan (CPT-11), bolus 5-fluorouracil (5-FU) and folinic acid (FA) (Saltz regimen) has recently been questioned as first-line chemotherapy for metastatic colorectal cancer after high early death rates due to gastrointestinal and thromboembolic events were reported in two US trials. Therefore, we carefully evaluated the safety and efficacy of this regimen, with high value placed on the management of delayed diarrhea. Forty-six patients with metastatic colorectal cancer received this first-line treatment in nine German outpatient clinics. Dose reductions were mandatory from the first cycle in case of toxicity grade >2. Chemotherapy was administered only to diarrhea-free patients. During a total of 175 cycles administered treatments were delayed for 1 week in 11.6% and given at a reduced dose in 14.5%. All and 40 patients were evaluable for toxicity and response, respectively. Grade 3/4 toxicities included diarrhea (n=10), leukopenia (n=9), neutropenia (n=3) and anemia (n=4). One non-fatal pulmonary embolism occurred. Four complete responses (CR) and 10 partial responses were seen, for an overall response rate of 35%. In addition, 16 patients (40%) had stable disease. Resectability of liver metastases was achieved in three patients, including one pathologically confirmed CR. Median progression-free and overall survival were 5 and 13 months, respectively. We conclude that outpatient treatment with the Saltz regimen was well tolerated. Severe gastrointestinal toxicity and thromboembolic events were rarely observed and never fatal. As down-staging was possible, combinations of CPT-11 and FA/5-FU should be further investigated in neoadjuvant protocols.
authors.affiliation: Outpatient Clinic of the Department of Internal Medicine I, University of Mainz, Mainz, Germany. moehler@mail.uni-mainz.de
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Tanja
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Christine
authors.initials: C
authors.lastname: Zanke
authors.forename: Horst
authors.initials: H
authors.lastname: Hohl
authors.forename: Helmut
authors.initials: H
authors.lastname: Burg
authors.forename: Peter
authors.initials: P
authors.lastname: Ehscheid
authors.forename: Peter
authors.initials: P
authors.lastname: Schwindt
authors.forename: Bernd
authors.initials: B
authors.lastname: Adami
authors.forename: Martin
authors.initials: M
authors.lastname: Schroeder
authors.forename: Ortwin
authors.initials: O
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Baldus
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Michael
authors.initials: M
authors.lastname: Heike
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care / Q000706:statistics & numerical data; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin