natriuretic-peptide--brain and Carcinoma--Non-Small-Cell-Lung

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

Since lung cancer surgery is still associated with a high complication rate, it is important to efficiently identify patients at high risk for postoperative complications following lung cancer surgery. We previously reported that elderly patients with elevated preoperative B-type natriuretic peptide (BNP) levels (>30 pg/mL) have an increased risk for postoperative atrial fibrillation and cardiopulmonary complications following lung cancer surgery. The objective of this study was to evaluate the clinical utility of BNP-guided risk classification for postoperative complications after lung cancer surgery.. A total of 675 consecutive patients who underwent curative surgery for lung cancer in two specialized thoracic centers between 2007 and 2011 were included in this retrospective study. We evaluated the association between the incidence of postoperative complications and preoperative BNP levels.. Univariable and multivariable stepwise logistic regression analyses revealed that an elevated preoperative BNP level was the most significant predictor of postoperative complications. All patients were classified by their preoperative BNP levels into a normal group (<30 pg/mL), a mildly elevated group (30-100 pg/mL), and a severely elevated group (>100 pg/mL). The incidence of postoperative complications was significantly higher in the severely and mildly elevated groups than in the control group (85 % and 47 % vs. 11 %, P < 0.0001). Furthermore, there were more severe complications and a higher mortality rate in the severely elevated group.. Risk assessment using preoperative BNP levels was clinically useful for the identification of patients at high risk for postoperative complications.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Atrial Fibrillation; Biomarkers; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Pneumonectomy; Pneumonia; Predictive Value of Tests; Preoperative Period; Respiratory Distress Syndrome; Retrospective Studies; Risk Assessment; ROC Curve; Thoracic Surgery, Video-Assisted; Thoracotomy; Young Adult

Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.. We describe a case of post-operative local recurrence of lung adenocarcinoma in an 81 year-old male. He underwent radiation and received chemotherapy with docetaxel, but neither treatment regimen was effective. Following identification of ALK rearrangements, crizotinib treatment was initiated. After treatment with crizotinib for 5 days, adverse events including acute renal failure (grade 2/CTCAE ver4.0) and congestive heart failure (grade 3) occurred. Crizotinib modified treatment was required. Half dose of crizotinib treatment could not control tumor progression. Ultimately, crizotinib was administrated at a dose of 250 mg twice daily every 3 day dosing for 13 months with maintenance of the anti-tumor effect.. This is the first case report that skip schedule was more effective than dose reduction daily in crizotinib administration for ALK rearranged NSCLC patient with severe adverse events.

Topics: Aged, 80 and over; Anaplastic Lymphoma Kinase; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Crizotinib; Drug Administration Schedule; Gene Rearrangement; Humans; Lung Neoplasms; Male; Natriuretic Peptide, Brain; Pyrazoles; Pyridines; Radiography; Receptor Protein-Tyrosine Kinases; Treatment Outcome

B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) are important diagnostic tools for patients with suspected cardiac disorders. The aim of this study was to evaluate the predictive value of plasma NT-pro-BNP in identifying cardiac metastases in patients with non-small cell lung cancer (NSCLC) and dyspnoea.. A total of 120 patients, median age 62 years (range 46-83), with NSCLC and dyspnoea were studied. Patients with heart failure or documented coronary artery disease were excluded. Echocardiographic imaging was used to detect cardiac metastases and estimate global left ventricular function. Ejection fraction and E/A ratio from transmitral inflow pattern were calculated. Plasma NT-pro-BNP was also measured. 72 patients (72/120, 60%) with cardiac metastases were identified.. NT-pro-BNP was significantly higher in patients with metastases (1347.5 +/- 1004.30 pg/ml vs. 159.02 +/- 93.29 pg/ml; p = 0.001). No differences between groups, regarding s-creatinine (p = 0.45), haemoglobin (p = 0.71), left ventricular hypertrophy (p = 0.91), and diastolic dysfunction (p = 0.79), were observed.. Plasma NT-pro-BNP is remarkably elevated in patients with NSCLC and myocardial/pericardial infiltrations and may be used as a sensitive marker for detecting cardiac metastases in these patients.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Heart Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity

To evaluate the value of the myocardial biochemical markers including creatine kinase MB isoenzyme (CK-MB), cardiac isoform of Tropnin-T (cTnT) and N-termimal pro-brain natriuretic peptide (NT-proBNP) and electrocardiogram (ECG) in monitoring the cardiotoxicity of recombinant human endostatin (rh-endostatin) in cancer patients.. Forty cancer patients were divided into two groups and received rh-endostatin in addition to chemotherapy (group A, n=24) or chemotherapy only (Group B, n=24). Serum CK-MB, cTnT levels and plasma NT-proBNP levels were measured and the ECG was recorded in all the patients before and after each of the two therapy cycles.. In group A, serum CK-MB, cTnT and plasma NT-proBNP levels were significantly increased after the treatment in comparison with the baseline levels (P<0.05), but such increment was not observed in group B (P>0.05). With comparable baseline levels of CK-MB, cTnT and NT-proBNP before the treatment (P>0.05), patients in group A showed significantly higher levels of the indices than those in group B after each therapy cycle (P<0.05). Increased ECG abnormality were observed after rh-endostatin treatment in Group A (P<0.05) at a rate significantly higher than that of Group B after the second treatment cycle (P<0.05).. Rh-endostatin has definite cardiotoxicity, and detection of the myocardial biochemical markers of CK-MB, cTnT and NT-proBNP may help predict the occurrence of cardiotoxicity.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Creatine Kinase, MB Form; Endostatins; Female; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Ovarian Neoplasms; Peptide Fragments; Recombinant Proteins; Risk Assessment; Troponin T

Cardiotoxicity is a known consequence of thoracic irradiation and there are multiple overlapping risk factors for cardiac disease and thoracic malignancies. In this study, we quantified the impact of thoracic (chemo)radiation on cardiac troponin T (TnT), creatine kinase-myocardial band (CK-MB) and aminoterminal pro-brain natriuretic peptide (NT-proBNP). Thirty patients receiving radiation therapy to the thorax with or without concurrent chemotherapy were evaluated. Serum was collected at baseline, 2 weeks into treatment and at the completion of radiation therapy. TnT, CK-MB and NT-proBNP were quantified using commercially available immunoassays. Cardiac dosimetric parameters and clinical risk factors were examined. In 29 of 30 patients, serum TnT remained undetectable (<0.01ng/mL) throughout (chemo)radiation. In the one patient with detectable serum TnT, levels did not change significantly with treatment. Similarly, thoracic (chemo)radiation did not cause statistically significant elevations in serum CK-MB and NT-proBNP. Thus, contemporary thoracic (chemo)radiation does not commonly result in elevations of serum TnT, CK-MB or NT-proBNP. Elevations in these markers during treatment merit further evaluation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Creatine Kinase, MB Form; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Factors; Small Cell Lung Carcinoma; Thymus Neoplasms; Troponin T