natriuretic-peptide--brain and Digestive-System-Neoplasms

rhuMAb 2C4 (pertuzumab, RO4368451), a human epidermal growth factor receptor-2 (HER2) targeted antibody that binds to an epitope distinct from trastuzumab, blocks ligand-associated heterodimerization of HER2 with other HER receptor family members. This study evaluated the toxicity, pharmacokinetics and anti-tumor activities of pertuzumab in Japanese patients with solid tumors.. Patients with solid tumors refractory to standard therapy were administered pertuzumab 5, 10, 15, 20 and 25 mg/kg intravenously once every 3 weeks. Grade 3 toxicities were considered as dose limiting. The maximum tolerated dose (MTD) was a dose at which two out of six patients had Grade 3 toxicities.. Eighteen patients, aged 38-66 (median 57) years, with solid tumors were enrolled and a total of 32 cycles of pertuzumab were administered. Toxicities were generally acceptable. Grade 3 elevation of gamma-glutamyl transpeptidase was observed in one patient at 25 mg/kg and was considered to be dose limiting. MTD was not reached up to a dose level of 25 mg/kg. The serum concentration of pertuzumab declined slowly (terminal half-life is approximately 3 weeks). The AUC proportionally increased over the dose range tested. There was limited evidence of activity (stable disease 2; progressive disease 13; and not evaluable 3); however, tumor shrinkage and tumor marker decrease were observed in an ovarian cancer and a non-small-cell lung cancer patient, respectively.. Pertuzumab is well tolerated up to 25 mg/kg. Although objective tumor response was not observed, it is worth evaluating as a flat dose and in combination with other cytotoxics and molecular-targeted agents.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Area Under Curve; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Diarrhea; Digestive System Neoplasms; Drug Eruptions; Female; Humans; Hypersensitivity; Lung Neoplasms; Lymphopenia; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Unknown Primary; Ovarian Neoplasms; Radiotherapy, Adjuvant; Receptor, ErbB-2

It is difficult to evaluate the tolerance to anesthesia of patients undergoing operations, who have risk factors of congestive heart failure, such as hypertension, old age or various cardiac diseases. BNP (B type natriuretic peptide) is a useful biomarker as a screening tool for LV dysfunction. Therefore we hypothesized that the measurement of BNP may be useful for perioperative management of these patients.. Subjects were 101 (58 male and 43 female) gastro-intestinal cancer patients, aged 30 to 91 years (mean 63.9 +/- 12.4) scheduled for intraperitoneal surgery. All patients' plasma BNP concentrations were measured when the patient agreed to the operation. Forty-five patients were enlisted for remeasurements on 2 or 4 postoperative days. We checked patients' backgrounds, perioperative circulatory characteristics and cardiac events. The relationship of BNP to other characteristics and cardiac events were analyzed.. The preoperative mean BNP of patients under 55 years of age (n=20) was 20.4, in patients age 55 to 74 (n=60) it was 30.4, and in patients 75 years and over (n=21) it was 162.1. BNP in elderly patients was higher than in the younger. The mean BNP of the 44 patients with some complications (hypertension, ECG abnormality, cardiac disease etc.) was 97.8, as compared to 23.3 in the 57 patients without complications. The BNP was higher in patients who were elderly, had some cardiac disease, lower exercise capacity, chest X ray abnormality or who needed an echo cardiographic examination. Among the 45 patients who were checked pre and postoperatively, 19 patients' BNP increased postoperatively, while 26 patients showed no change or decrease. Excluding 2 patients, with newly onset congestive heart failure during the postoperative period, the preoperative mean BNP was 63.5, and the postoperative mean BNP was 54.6. During the perioperative period, there was no significant change of BNP. There was no relationship between the BNP and perioperative circulatory characteristics or cardiac events. There were 5 cases with high BNP levels (> 300). None of these patients had cardiac symptoms, and they had normal LV systolic function. It is probable that these patients had chronic heart failure due to LV diastolic dysfunction and risks of perioperative heart failure.. We cannot predict any circulatory characteristics and cardiac events from preoperative BNP measurement; however BNP measurement is useful for screening asymptomatic chronic heart failure due to LV diastolic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia; Biomarkers; Chronic Disease; Digestive System Neoplasms; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Perioperative Care; Postoperative Complications; Risk Factors; Ventricular Dysfunction, Left