Oxicities All 20 patients had been evaluated for safety (Table 4). Probably the most prevalent
Oxicities All 20 sufferers were evaluated for safety (Table four). Probably the most widespread toxicities regarded as at the least possibly related to study drug had been 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 ). Most of the toxicities (84 ) were either grade 1 or 2 and in most instances (41 of 46 grade 1 or 2 events) had been reported in patients treated at dose level 2. Critical grade three toxicities that have been at least possibly related to study drug are rash (n=5); acute infusion MT1 drug reaction (n=2); and, hand-foot skin reaction (n=2). All of those had been reported at dose level two; except for one patient with rash. There were no drug-related grade four toxicities or deaths reported. There have been three DLT’s, all at dose level 2. One particular patient (case #11, Table three) had an anaphylactic reaction for the duration of the very first infusion of cetuximab. Subsequently, the patient had a myocardial infarction with elevated troponins and was taken off study. A second patient (case #4, Table 3) had developed an acute hypersensitivity reaction throughout the very first infusion of cetuximab and was subsequently continued on erlotinib alone. A third patient (case #7, Table 3) had a grade 3 rash that resolved with antibiotics. Throughout the phase I study, dose level two was established as MTD (erlotinib 150 mg oral daily and cetuximab 250 mgm2 IV on days 1, 8, 15, and 22 right after a loading dose of 400 mgm2 IV)(19). Consequently, the suggested phase II dose was erlotinib 150 mg oral daily and cetuximab 250 mgm2 IV on days 1, eight, 15, and 22 following a loading dose of 400 mgm2 IV. Antitumor activity All 20 treated sufferers have been integrated in the efficacy evaluation. Fourteen on the 20 individuals had at least 1 post-treatment imaging evaluation, and 3 individuals came off study prior to post-treatment imaging evaluation due to clinical progression. The remaining three individuals have been taken off study for the following reasons: withdrawal of consent (n=2) and adverse occasion (acute infusion reaction, n=1). These sufferers had been thought of as therapy failures.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptMol Cancer Ther. Author manuscript; offered in PMC 2014 August 19.PKD3 Gene ID Wheler et al.PageThe greatest overall responses (n=20) are illustrated in Figure 1. From the 20 individuals, two individuals (ten ) attained PR for 24.two and 7.four months. Also, 3 patients (15 ) attained SD6 months (13.7, 7.7 and 6.3 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 patients who had progressed previously on single-agent erlotinib, a single patient (six.7 ; case #17, Table three) attained SD6 months on this study. The duration of remedy 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, a single patient accomplished PR and two individuals attained SD6months. A single patient (case #2, Table 3; Figure 2) had a recognized EGFR TKI-resistant mutation (insertion in exon 20, D770GY) and accomplished a PR (-33 ; duration=24.2 months). This patient had previously received two lines of standard chemotherapy but had not received prior EGFR inhibitor therapy. A second patient (case #17, Table 3) had a recognized EGFR TKI-sensitive mutation (L858R) in exon 21 and has ongoing SD6 months (-23 ; duration=7.7 months). This patient had recei.