7%) and 17 (56.7%) patients, respectively. Only six patients (20.0%) required dose interruption because of toxicity related to gefitinib
(diarrhea, acne, and erythema). Eleven patients (36.7%) required interruption in celecoxib therapy due to toxicity (hepatitis, vomiting, nausea, and gastric pain). Eleven patients required interruption in gefitinib therapy and six patients required interruption in celecoxib therapy for reasons other than toxicity, such as disease progression, surgery, and non-related toxicity. Five patients had their dose of celecoxib reduced (three cases due to toxicity, one case due to mental confusion, and one case due to patient misunderstanding of required dosing). Inhibitors,research,lifescience,medical Safety and tolerability In total, 28 patients (93%) experienced ≥1 AE during Inhibitors,research,lifescience,medical the study, most of which were mild
to moderate in severity (Table 2). AEs were considered related to gefitinib in 20 (67%) patients and celecoxib in 11 (36.7%) patients. The most frequent AEs considered related to gefitinib were grade 1/2 acne and diarrhea. The most frequent AEs considered related to celecoxib Inhibitors,research,lifescience,medical were grade 1/2 stomatitis, nausea, diarrhea, and upper abdominal pain. Twelve patients (40%) experienced CTC grade 3/4 AEs (including fatigue, hepatitis, chest pain, pneumonia, perineal abscess, diarrhea, vomiting, hypertension, and abdominal pain). However, grade 3/4 AEs were considered by the investigator to be possibly related to gefitinib in only two patients; both grade 3 acne and folliculitis in one patient; and both grade 3 diarrhea and hypotension in one patient. One patient experienced grade 3 beta-catenin activation celecoxib-related hepatitis. Table 2 Drug-related AEs occurring Inhibitors,research,lifescience,medical in ≥5% of patients (and all grade 3/4 AEs) Of the three patients who required a reduction in the dose of celecoxib due to toxicity, one had a history of gastric sensitivity (dose was halved to 200 mg bid). No patients were withdrawn and there were no deaths due to AEs. Efficacy All 30 patients were
included in the intent-to-treat population Inhibitors,research,lifescience,medical and were evaluable for efficacy. Twelve patients (40%) were classified as having stable all disease during follow-up and 18 patients (60%) had progressive disease. The median TTP was 69 days (95% CI: 49-97) (Figure 1A). Figure 1 (A) TTP and (B) overall survival in 30 patients with GI tumors treated with gefitinib (250 mg/day) and celecoxib (400 mg bid). bid, twice daily; CI, confidence interval; GI, gastrointestinal; TTP, time to progression. Sixty percent of the patients (95% CI: 43-78) were alive at six months. The median overall survival time was 241 days; however, the 95% CI could not be estimated for this value due to censored data (Figure 1B). EGFR and COX-2 immuno-expression: relationship with tumor response EGFR and COX-2 immuno-expression was evaluable for 20 and 21 patients, respectively.