Are we turning to more than a first line treatment of metastatic colorectal cancer with high dose irinotecan?: A monocentric institution safety analysis of 46 patients.
OBJECTIVE
Irinotecan (CPT11) at 180 mg/m(2) with LV5FU2 for metastatic colorectal cancer (MCRC) has response rates (RRs) of 56 and 4% as first- and second-line treatments, respectively [1-2], and higher doses of CPT11 result in higher RRs. The present cohort analysis aimed to evaluate the effect of increasing doses of this combination treatment in clinical practice.


METHODS
Chemo-naive and pretreated patients with MCRC received CPT11 and LV5FU2 (5FU 48-h CI 2400 mg/m(2), D1 bolus leucovorin 200 mg/m(2)), followed by 5FU 400 mg/m(2) (cycles d1-d15). CPT11 dose was increased by 20 mg/m(2) at each cycle, from 180 mg/m(2) up to 260 mg/m(2), unless grade 3 toxicities other than alopecia arose.


RESULTS
Between March 2002 and September 2005, 46 patients were recruited (median age: 62.3 years). A total of 512 cycles of chemotherapy were administered (median: 9 cycles/patient; range: 3-41). Median follow-up was 16.2 months. Altogether, 27 patients had received prior chemotherapy: 24 with an oxaliplatin-based regimen; seven with CPT11; and five with LV5FU2 or oral 5FU. Doses of 260 mg/m(2) were used in 17 patients, 240 mg/m(2) in seven, 220 mg/m(2) in six and 200 mg/m(2) in five, while 11 remained at 180 mg/m(2); 121 cycles used 260 mg/m(2) (24%), with 76 cycles at 240 mg/m(2) (14%), 78 cycles at 220 mg/m(2) and 58 cycles at 200mg/m(2). The objective response (OR) was 40%, with stable disease (SD) in 45% and disease progression (DP) in 11%. In the first-line therapy group, partial/complete responses were 55%, with SD in 30% and DP in 15%. In pretreated patients, OR was 30.5%, SD was 58.5% and DP was 11%. Nine patients (20%) had a therapeutic break (median: 5.1 months; range: 3-10). Overall median survival was 17 months, with 16.5 months in pretreated patients and 19.6 months in the first-line group. Toxicity grades 3-4 and overall incidence per cycle were: neutropenia, 3-22%; diarrhea, 4-22%; vomiting, 2-20%; alopecia, 20-26%; anemia, 0.2-2%; thrombocytopenia, 0-0%; and mucositis, 0.4-2.2%.


CONCLUSIONS
The toxicity of high-dose CPT11+LV5FU2 chemotherapy was well tolerated when the dose was progressively increased according to individual tolerability, with 37% of patients receiving CPT11 at 260 mg/m(2). Progression-free survival (PFS) increased with higher doses of CPT11. In the chemo-naive and pretreated subgroups, the median PFS was 10.9 and 8.8 months, respectively (P=0.698, NS). Optimization of CPT11 doses in pretreated patients appears to pave the way for new treatment options.
Gastrointestinal and liver oncology-radiotherapy unit, institut Sainte-Catherine, chemin du Lavarin, 84000 Avignon, France. Laurent.mineur@isc84.org
L
L
Mineur
R
R
Sabatier
S
S
Kirscher
F
F
Plat
Y
Y
Goubely
N
N
Molinari
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin