This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m À2 at week 1 and 250 mg m À2 weekly thereafter until disease progression. Oxaliplatin (100 mg m À2 ) and leucovorin (100 mg m
À2) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m À2 ) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1 -65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5 -6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-a levels showed a 100% RR compared to 37.0% in the remaining 27 patients (Po0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.
Sorafenib showed antitumor activity in this population of imatinib and sunitinib pretreated GIST. With sorafenib, about one third of patients can maintain disease control for more than 24 weeks.
Background:We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.Methods:Among MGC patients (n=108), who received S-1 (40 mg m−2 b.i.d., days 1–14) and cisplatin (60 mg m−2, day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).Results:Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3% P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.Conclusion:Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.
A long time-to-progression and first-line chemotherapy were significant protective factors against re-stenosis. In chemotherapy-naïve gastric cancer patients with pyloric obstruction, placement of an uncovered stent followed by chemotherapy can be considered to increase stent patency.
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