Merck KGaA offers reviewed the publication as well as the sights and views described in the publication usually do not necessarily reflect those of Merck KGaA
Merck KGaA offers reviewed the publication as well as the sights and views described in the publication usually do not necessarily reflect those of Merck KGaA. This work was presented previously as an oral presentation on the European Cancer Organisation (ECCO) 15/European Society for Medical Oncology (ESMO) 34 meeting in Berlin, Germany, 20C24 September, 2009, with the 2008 Annual Meeting from the American Society of Clinical Oncology, June 3 May 30 to, 2008 in Chicago, Illinois (abstract 15027). Footnotes (C/A)Consulting/advisory romantic relationship(RF)Research financing(E)Work(H)Honoraria received(OI)Possession interests(IP)Intellectual real estate rights/inventor/patent holder(SAB)Scientific advisory board Author Contributions Conception/Style: Javier Sastre, Eduardo Daz-Rubio Provision of research material or sufferers: Javier Sastre, Cristina Grvalos, Fernando Rivera, Bartomeu Massuti, Manuel Valladares-Ayerbes, Eugenio Marcuello, Jos L. was motivated in 58 sufferers (88%). Fourteen of 29 sufferers with wild-type tumors responded (48.3%; 95% self-confidence period [CI], 29.4%C67.5%), weighed against six of 29 sufferers with mutant tumors (20.7%; 95% CI, 8.0%C39.7%). The median progression-free success (PFS) period was 7.1 months. The median PFS period for sufferers whose tumors had been wild-type was considerably longer than for all those with mutant tumors (8.4 months versus 6.0 months; = .024). The high occurrence of serious paronychia (29.6%) declined (7.7%) after capecitabine dosage adjustment. Conclusions. Capecitabine plus Cetuximab at a dosage of just one 1, 000 mg/m2 every 12 hours may be an alternative solution to more aggressive regimens in older sufferers with advanced wild-type CRC. tumors. Predicated on these data, an additional subgroup analysis according to position was is and done also presented right here. GANT 58 Sufferers and Strategies Regional ethics committee acceptance was attained before enrollment of any sufferers in to the research, which was performed in accordance with the Declaration of Helsinki and its subsequent amendments as well as Good Clinical Practice Guidelines. Signed informed consent was obtained from all patients before study entry. Patient Selection Inclusion criteria included: histologically confirmed metastatic nonresectable colorectal adenocarcinoma; age 70 years; the absence of previous treatment for advanced disease; at least one measurable lesion by World Health Organization (WHO) criteria; a Karnofsky performance status score of 80%C100%; an interval 12 months after the end of adjuvant chemotherapy; a life expectancy 3 months; adequate bone marrow, renal, and hepatic functions (neutrophils 1.5 109/L, hemoglobin 9 g/dL, platelets 100 109/L, total bilirubin 1.5 upper limit of normal [ULN], aspartate aminotransferase and alanine aminotransferase 2.5 ULN or 5 ULN in cases of liver metastases), and a serum creatinine clearance (CrCl) 30 mL/minute by the CockroftCGault method. Exclusion criteria were: brain or leptomeningeal metastases; other malignancy except basal cell skin carcinoma or in situ carcinoma of the cervix; malabsorption; inflammatory intestinal disease; previous administration of anti-EGFR therapy; serious concomitant disease such as unstable heart disease, acute myocardial infarction in the last 12 months, uncontrolled active infection, or severe neurologic or psychiatric disorders; and the presence of one or more criteria for frailty(a) dependent for activities of daily living according to the Katz scale; (b) the presence of three or more of the following comorbid conditions: congestive heart failure, other chronic heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, peripheral neuropathy, chronic renal failure, hypertension, diabetes, systemic vasculitis, and severe arthritis; and (c) the presence of geriatric syndromes such as dementia, delirium in stressful situations, fecal or urinary incontinence GANT 58 in the absence of infection, the use of GANT 58 diuretics or laxatives or benign prostatic hyperplasia, severe depression, frequent falls, spontaneous bone fractures, and neglect. Treatment Schedule Cetuximab was administered i.v. at an initial dose of 400 mg/m2 body surface area as a 2-h i.v. infusion followed by weekly i.v. doses of 250 mg/m2. Premedication with an i.v. antihistamine was mandatory. Capecitabine was taken orally, 2 weeks on and 1 week off, at a dose of 1 1,250 mg/m2 every 12 hours for patients with a CrCl 50 mL/minute or 950 mg/m2 every 12 hours GANT 58 in cases of a CrCl of 30C50 mL/minute. During the trial, the protocol was amended for safety reasons, reducing the dose of capecitabine to 1 1,000 mg/m2 every 12 hours in patients with a CrCl 50 mL/minute and 750 mg/m2 every 12 hours in cases with a CrCl of 30C50 mL/minute. Treatment was maintained until disease progression, unacceptable toxicity, or withdrawal of patient consent. The cetuximab dose was reduced to 200 mg/m2 in cases of a second episode of Mouse monoclonal to LAMB1 grade 3 cutaneous toxicity and to 150 mg/m2 if repeated. Cetuximab was delayed until the patient recovered to grade 0C1 toxicity. Capecitabine was reduced by 25% in cases of a grade 3 or second episode of grade 2 nonhematologic toxicity and by 50% if a grade 4 or a second episode of grade 3 nonhematologic toxicity occurred. Capecitabine was also reduced by 25% in cases of grade 2 hand-foot syndrome and by 50% after a second episode of the same toxicity. Study Evaluations In the 14 days before the first infusion, patients underwent a clinical history and physical examination, assessment using the Independent Daily Activities Katz Scale, comorbidity evaluation, blood count measurements, liver and renal function tests, carcinoembryonic antigen (CEA) level measurement, and evaluation of their prothrombin time and electrolytes. An abdominal computed tomography (CT) scan together with a chest x-ray or chest CT scan were performed within 28 days before treatment commencement. During the treatment period, blood counts and biochemical parameters were determined every 3 weeks, and.