Safety and efficacy of outpatient treatment with CPT-11 plus bolus folinic acid/5-fluorouracil as first-line chemotherapy for metastatic colorectal cancer.
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.
Moehler
Markus
M
Outpatient Clinic of the Department of Internal Medicine I, University of Mainz, Mainz, Germany. moehler@mail.uni-mainz.de
Hoffmann
Tanja
T
Zanke
Christine
C
Hohl
Horst
H
Burg
Helmut
H
Ehscheid
Peter
P
Schwindt
Peter
P
Adami
Bernd
B
Schroeder
Martin
M
Klein
Ortwin
O
Baldus
Michael
M
Galle
Peter R
PR
Heike
Michael
M
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
D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin