晚期胃癌化疗联合靶向治疗的策略.pptVIP

* PFS（progression-free survival）是指观察受试者进入试验到肿瘤发生恶化或死亡的时间长度，受试者只要“肿瘤恶化”或“死亡”二者其一先发生，则达到研究的终点；TTP(time to progression)定义事件仅有“肿瘤恶化”，不包括“死亡”，故若受试者尚未发生“肿瘤恶化”就已经先“死亡”，则此为受试者再也观察不到“肿瘤恶化”，故他提供的资料是不完整的TTP时间资料，统计上称cenoring。TTF（time to treatment failure）这一指标所定义事件为“退出试验”，由于退出试验的原因可能包含疗效、毒性、安全性等等，不单单展现药物疗效，因而不建议用于疗效确认性试验。 * Background: The prognosis of advanced gastric cancer (GC) patients (pt) is still poor despite the introduction of new chemotherapy regimens. In colorectal cancer (CRC) it has been demonstrated that KRAS or BRAF mutations are associated with resistance to treatment with the anti-EGFR mAbs. We have assessed whether, and to what extent, the mutational profile of KRAS and BRAF genes affects the response to cetuximab combination therapy in GC. Methods: We have collected 44 tumor samples from pts affected by locally advanced or metastatic GC undergoing cetuximab combination therapy as first-line treatment in two consecutive phase II studies. Thirteen pts received cetuximab plus FOLFIRI (FOLCETUX Study) and 31 pts cetuximab plus cisplatin and docetaxel (DOCETUX Study). Genomic DNA was extracted from paraffin-embedded tumor specimens from all cases. The mutational status of KRAS (exon 2) and BRAF (exon 15) was ascertained by PCR amplification followed by direct sequencing. The objective response was evaluated every 6 weeks by CT according to RECIST criteria. Results: KRAS and BRAF mutations were detected in 5 (11.4%) and 1 (2.3%), respectively, of the 44 tumors analyzed. These frequencies are consistent with those previously reported in GC. In the case of KRAS, 3 cases displayed amino acid substitutions of codon 12 and 1 of codon 13. One case had the A11V variant that had been reported in hematopoietic and lymphoid tissue of the stomach. The only BRAF mutation found in 1 sample was the classic V600E substitution. As a whole, 13.6 % of the analyzed tumors carried a mutation in either KRAS or BRAF genes. K-RAS and BRAF mutations were, as expected, mutually exclusive.