ABSTRACT
PURPOSE: Phase II/III studies have shown XELOX to be as effective as FOLFOX in patients with advanced colorectal cancer (CRC). The study was designed to evaluate the activity and tolerability of XELOX in CRC. In August 2002, we began a prospective study of XELOX as first-line therapy for patients with metastatic CRC. Twenty-two patients were enrolled between November 2002 and August 2003 (series I). An interim analysis performed in August 2003 revealed that 32% of patients required a dose reduction of oxaliplatin because of toxicity. From August 2003 to April 2005, an additional 20 patients were included (series II). This second group of patients received oxaliplatin at a lower dose. PATIENTS AND METHODS: The first 22 patients (series I) included received oxaliplatin 130 mg/m(2) on day 1 plus capecitabine 2000 mg/m(2) daily on days 1-15 (3-week cycle). The second set of 20 patients (series II) received oxaliplatin 85 mg/m(2) on day 1; the dose of capecitabine and the frequency of administration were not modified. RESULTS: Patient characteristics were well balanced in the 2 series. Overall response (series I vs. II): 41% vs. 65%; median time to progression was similar: 10.51 vs. 10.92 (log-rank test, P = .79). Median survival was similar in the 2 series: 19.55 vs. 21.18 months (log-rank test, P = .61). Grade 3/4 toxicity (series I vs. II): peripheral neuropathy, 14% vs. 0 (P = .23). CONCLUSION: In patients with advanced CRC, in combination with capecitabine, oxaliplatin 85 mg/m(2) is as effective with lower toxicity when compared with oxaliplatin 130 mg/m(2).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Capecitabine , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Combinations , Drug-Related Side Effects and Adverse Reactions , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/pharmacology , Humans , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/pharmacology , Oxaloacetates , Survival AnalysisABSTRACT
BACKGROUND/AIMS: Oxaliplatin damages the DNA, leading to apoptosis. XPA, XPD, ERCC1 and XPG genes are involved in DNA repair, and single nucleotide polymorphisms (SNPs) in these genes can influence the efficacy of oxaliplatin. We examined SNPs in these genes and correlated the results with time to progression (TTP), overall survival and response to oxaliplatin in 42 advanced colorectal cancer patients (CRC) treated with first-line oxaliplatin/fluoropyrimidine. METHODS: DNA was obtained from peripheral blood cells, and the allelic discrimination assay was used to analyze the XPA 5'UTR T/C, XPD Lys751Gln, ERCC1 Lys259Thr and XPG, C/T. RESULTS: Patients with XPG C/C genotype had a longer survival (p = 0.001) and TTP (p = 0.009) than patients with XPG C/T or T/T genotypes, and patients with both XPG C/C and XPA T/C or C/C genotypes had a longer survival (p = 0.0001) and TTP (p = 0.0001) than patients with other genotypes. XPG (CC) combined with XPA (TC/CC) genotypes showed an independent role for TTP (relative risk, RR = 6.38; p = 0.0001) and survival (RR = 34; p = 0.0005). CONCLUSION: Polymorphism in XPG combined with XPA may be an important prognosticator of clinical outcome following oxaliplatin/ fluoropyrimidine chemotherapy. Further studies in larger patient cohorts are warranted to confirm their role in CRC.
