Oxicities All 20 individuals had been evaluated for safety (Table four). Probably the most typical
Oxicities All 20 individuals have been evaluated for safety (Table 4). The most prevalent toxicities deemed at the least possibly related to study drug were rash (n=9, 45 ); diarrhea (n=7, 35 ); hypomagnesemia (n=6, 30 ); fatigue (n=6, 30 ); nausea (n=4, 20 ); and, anorexia (n=3, 15 ). Many of the toxicities (84 ) were either grade 1 or 2 and in most instances (41 of 46 grade 1 or two events) had been reported in NPY Y4 receptor custom synthesis patients treated at dose level 2. Significant grade 3 toxicities that have been a minimum of possibly associated with study drug are rash (n=5); acute infusion reaction (n=2); and, hand-foot skin reaction (n=2). All of those have been reported at dose level 2; except for one patient with rash. There had been no drug-related grade four toxicities or deaths reported. There have been three DLT’s, all at dose level 2. One patient (case #11, Table three) had an anaphylactic reaction during the very first infusion of cetuximab. Subsequently, the patient had a myocardial infarction with elevated troponins and was taken off study. A PLK1 site second patient (case #4, Table three) had developed an acute hypersensitivity reaction during the initial infusion of cetuximab and was subsequently continued on erlotinib alone. A third patient (case #7, Table 3) had a grade three rash that resolved with antibiotics. For the duration of the phase I study, dose level two was established as MTD (erlotinib 150 mg oral day-to-day and cetuximab 250 mgm2 IV on days 1, 8, 15, and 22 following a loading dose of 400 mgm2 IV)(19). As a result, the encouraged phase II dose was erlotinib 150 mg oral every day and cetuximab 250 mgm2 IV on days 1, 8, 15, and 22 soon after a loading dose of 400 mgm2 IV. Antitumor activity All 20 treated individuals had been integrated inside the efficacy evaluation. Fourteen from the 20 patients had no less than 1 post-treatment imaging evaluation, and three sufferers came off study prior to post-treatment imaging evaluation on account of clinical progression. The remaining 3 sufferers had been taken off study for the following causes: withdrawal of consent (n=2) and adverse event (acute infusion reaction, n=1). These patients have been considered as treatment failures.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptMol Cancer Ther. Author manuscript; offered in PMC 2014 August 19.Wheler et al.PageThe very best general responses (n=20) are illustrated in Figure 1. From the 20 individuals, two sufferers (10 ) attained PR for 24.two and 7.four months. Also, 3 patients (15 ) attained SD6 months (13.7, 7.7 and six.3 months). Responses in sufferers who had received prior EGFR inhibitors–Fifteen of your 20 patients (75 ) had received prior EGFR inhibitors (Table 3). Of 15 sufferers who had progressed previously on single-agent erlotinib, one patient (six.7 ; case #17, Table 3) attained SD6 months on this study. The duration of therapy was longer (7.7 months) on this combination study with dual EGFR inhibitors than on prior single-agent erlotinib (6.1 months). Responses in NSCLC patients with mutant EGFR–Of the nine sufferers with EGFR-mutant NSCLC, one patient achieved PR and two patients attained SD6months. One patient (case #2, Table three; Figure two) had a identified EGFR TKI-resistant mutation (insertion in exon 20, D770GY) and accomplished a PR (-33 ; duration=24.two months). This patient had previously received two lines of normal chemotherapy but had not received prior EGFR inhibitor therapy. A second patient (case #17, Table three) had a identified EGFR TKI-sensitive mutation (L858R) in exon 21 and has ongoing SD6 months (-23 ; duration=7.7 months). This patient had recei.