Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism.
OBJECTIVE
Inherited variations in drug metabolizing enzymes may influence drug efficacy. This phase II study assesses the impact of second-line weekly irinotecan (CPT-11)/docetaxel in non-small cell lung cancer (NSCLC) patients, and gauges the uridine diphosphate glucuronosyl transferase (UGT1A1) polymorphism influence in toxicity and antitumor activity.


METHODS
Fifty-one patients with NSCLC treated with at least one prior chemotherapy regimen were enrolled. Patients received irinotecan 70 mg/m(2) followed by docetaxel 25 mg/m(2). Both drugs were given on days 1, 8, and 15 every 28 days. UGT1A1 polymorphism were analyzed in blood samples of 47 patients. The UGT1A1 polymorphism are classified according to the number of TA repeats in the promoter region of this gene.


RESULTS
Three patients (6%) achieved a partial response and nineteen patients (37%) had stable disease. Median survival was 8 months (95% CI: 4.8-11.2) and 1-year survival 30%. Grade 3-4 hematologic toxicity was low (less than 10% of patients); 15% of patients had grade 3 asthenia and 25% of patients had grade 3/4 diarrhea. The frequency of UGT1A1 genotypes was as follows: 6/6 49%, 6/7 36%, and 7/7 15%. No differences in toxicity were observed according to UGT1A1 polymorphism. A nonsignificant improvement in time to progression (4 vs. 3 months) and median survival (11 vs. 8 months) was detected in patients with the variant alleles (6/7 and 7/7).


CONCLUSIONS
This weekly irinotecan/docetaxel regimen has shown an acceptable toxicity profile while encouraging median and 1-year survival in heavily pretreated NSCLC patients. The tendency to better prognosis in patients carrying the variant genotypes 6/7 and 7/7 of UGT1A1 gene requires further validation.
Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Albert
A
Font
José Miguel
JM
Sánchez
Miquel
M
Tarón
Eva
E
Martinez-Balibrea
José Javier
JJ
Sánchez
José Luis
JL
Manzano
Mireia
M
Margelí
Martin
M
Richardet
Agustí
A
Barnadas
Albert
A
Abad
Rafael
R
Rosell
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D000077143:Docetaxel; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D043823:Taxoids; D000099148:UGT1A1 Enzyme