Ients with adenocarcinoma histology versus 4 patients with squamous cell carcinoma. Mutation status was EGFR wild-type in seven individuals, EGFR-mutant in two individuals (exon 19 deletion, n=1; exon 20 insertion, n=1) and unknown in a single patient. Of those, two patients achieved PR (instances #2 and 15, Table three) and a single patient (case #10, Table 3) attained SD6 months (EGFR-mutant adenocarcinoma, n=1; EGFR wild-type squamous cell carcinoma, n=2).NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDiscussionPatients with known EGFR TKI-sensitive mutations in exon 19 and 21 respond effectively to matched therapy with EGFR inhibitors, but typically rapidly develop resistance. Preclinical research recommend that dual agent molecular targeting of EGFR using a combination of a TKIMol Cancer Ther. Author manuscript; accessible in PMC 2014 August 19.Wheler et al.Page(erlotinib/gefitinib) and an anti-EGFR antibody (cetuximab) might successfully overcome resistance(15, 16, 25). We conducted a phase I trial combining erlotinib and cetuximab in patients with advanced cancer(19). Herein, we report that five of 20 patients with NSCLC treated on this study achieved PR (n=2) or SD6 months (n=3). The combination of erlotinib and cetuximab was well tolerated. Probably the most frequently observed CXCR4 Agonist manufacturer toxicities that had been at least possibly associated with study drug have been rash (n=9); diarrhea (n=7); hypomagnesemia (n=6); fatigue (n=6); nausea (n=4); and, anorexia (n=3) (Table 4). The safety profile for the mixture was consistent with the individual security profile of every drug. These findings are comparable to those reported in another phase I study of gefitinib and cetuximab in individuals with refractory NSCLC, in which escalating doses of cetuximab have been combined with fixed dose of gefitinib(17). We defined the recommended phase II dose of erlotinib 150 mg oral everyday and cetuximab 250 mg/m2 IV on days 1, eight, 15, and 22 soon after a loading dose of 400 mg/m2 IV (dose level two), using the major side effect being rash. Among the 5 individuals who demonstrated antitumor activity (PR or SD6 months), two had EGFR wild-type (of your eight total with EGFR wild-type); each had squamous histology (of a total of 4 with this histology) and accomplished SD for 13.7+ months and also a PR for 7.4 months. The third patient had an EGFR TKI-resistant mutation in exon 20 (D770GY insertion; of a total of two with EGFR TKI-resistant mutation). Contrary towards the reality that insertions beyond the C-helix (beyond Tyr 764) with the EGFR kinase domain usually do not respond to usual doses of erlotinib or gefitinib (26, 27), this patient achieved a PR for 24.2+ months. Two other individuals had an EGFR TKI-sensitive mutation (L858R) in exon 21 and demonstrated SD for 7.7+ and 6.3+ months (the former had GSK-3α Inhibitor Storage & Stability failed prior erlotinib immediately after initial response plus the latter had not received prior EGFR therapy). 3 of 5 patients with PR/SD6 months had adenocarcinoma and two patients had squamous cell carcinoma. There are two prior clinical research evaluating a mixture of EGFR inhibitors in NSCLC(17, 18). Considerable response was not noted in individuals with acquired resistance to erlotinib. Although 11 of 13 individuals had SD (median PFS=3 months), including individuals with T790M mutation, prolonged stabilization of illness was not reported (18). In yet another study, stable disease was observed in four of 13 NSCLC individuals with wild-type EGFR disease (17); no PRs have been noticed. The difference in efficacy observed amongst these research and our study just isn’t entir.
