Purpose: Bcl-2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT-263) is a potent and selective inhibitor of Bcl-2 and Bcl-x L . The primary objectives of this phase IIa study included safety at the recommended phase II dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy. Experimental Design: Thirty-nine patients received navitoclax 325 mg daily, following an initial lead-in of 150 mg daily for 7 days. Study endpoints included safety and toxicity assessment, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. Results: The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade III–IV in 41% of patients. Partial response was observed in one (2.6%) patient and stable disease in 9 (23%) patients. Median PFS was 1.5 months and median OS was 3.2 months. A strong association between plasma pro–gastrin-releasing peptide (pro-GRP) level and tumor Bcl-2 copy number ( R = 0.93) was confirmed. Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, pro-GRP, and circulating tumor cell number as correlates of clinical benefit. Conclusion: Bcl-2 targeting by navitoclax shows limited single-agent activity against advanced and recurrent SCLC. Correlative analyses suggest several putative biomarkers of clinical benefit. Preclinical models support that navitoclax may enhance sensitivity of SCLC and other solid tumors to standard cytotoxics. Future studies will focus on combination therapies. Clin Cancer Res; 18(11); 3163–9. ©2012 AACR .

https://clincancerres.aacrjournals.org/content/clincanres/18/11/3163.full.pdf

Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

There is experimental evidence that volatile substances in human breath can reflect presence of neoplasma. Volatile aldehydes were determined in exhaled breath of 12 lung cancer patients, 12 smokers and 12 healthy volunteers. Alveolar breath samples were collected under control of expired CO(2). Reactive aldehydes were transformed into stable oximes by means of on-fiber-derivatization (SPME-OFD). Aldehyde concentrations in the ppt and ppb level were determined by means of gas chromatography-mass spectrometry (GC-MS). Exhaled concentrations were corrected for inspired values. Exhaled C(1)-C(10) aldehydes could be detected in all healthy volunteers, smokers and lung cancer patients. Concentrations ranged from 7 pmol/l (161 pptV) for butanal to 71 nmol/l (1,582 ppbV) for formaldehyde. Highest inspired concentrations were found for formaldehyde and acetaldehyde (0-55 nmol/l and 0-13 nmol/l, respectively). Acetaldehyde, propanal, butanal, heptanal and decanal concentrations showed no significant differences for cancer patients, smokers and healthy volunteers. Exhaled pentanal, hexanal, octanal and nonanal concentrations were significantly higher in lung cancer patients than in smokers and healthy controls (p(pentanal) = 0.001; p(hexanal) = 0.006; p(octanal) = 0.014; p(nonanal) = 0.025). Sensitivity and specificity of this method were comparable to the diagnostic certitude of conventional serum markers and CT imaging. Lung cancer patients could be identified by means of exhaled pentanal, hexanal, octanal and nonanal concentrations. Exhaled aldehydes reflect aspects of oxidative stress and tumor-specific tissue composition and metabolism. Noninvasive recognition of lung malignancies may be realized if analytical skills, biochemical knowledge and medical expertise are combined into a joint effort.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.24970

Breath gas aldehydes as biomarkers of lung cancer.

Clinical utility of cytokeratins as tumor markers.

PURPOSE: To synthesize the available randomized evidence on the efficacy of dexamethasone when used for protection against acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic cancer chemotherapy. MATERIALS AND METHODS: A meta-analysis was performed using trials identified through MEDLINE (1966 to April 1999), Embase, Derwent Drug File, and the Cochrane Library’s Database of Controlled Trials. Data on acute and delayed emesis and nausea were collected. All randomized studies comparing dexamethasone to placebo, no treatment, or other antiemetics qualified, including cross-over trials providing first-cycle data. RESULTS: Of 1,200 citations screened, 32 studies with 42 pertinent comparisons and 5,613 patients were included in the meta-analysis. Dexamethasone was superior to placebo or no treatment for complete protection from acute emesis (odds ratio, 2.22; 95% confidence interval [CI], 1.89 to 2.60) and for complete protection from delayed emesis (odds ratio, 2.04; 95%...

Contribution of Dexamethasone to Control of Chemotherapy-Induced Nausea and Vomiting: A Meta-Analysis of Randomized Evidence

Label-free photoelectrochemical immunoassay for CEA detection based on CdS sensitized WO3@BiOI heterostructure nanocomposite.

CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases. Except for NSE, all tumor markers showed a clear relationship with tumor stage and histology and therefore enabled a better histological diagnosis. Abnormal CEA serum levels were mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively.

Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis: Comparison with the main clinical and pathological prognostic factors

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis

Tumor markers (CEA, CA 125, CYFRA 21.1, SCC and NSE) in non small cell lung cancer (NSCLC) patients as an aid in histological diagnosis and prognosis: Comparison with the main clinical and pathological prognostic factors

1143 Background: Following the approval of bevacizumab for the treatment of MBC, this study was devised to identify the profile of patients (pt) treated under real conditions of use, their relation...

Multicentric, observational, transversal study to describe the clinical profile of patients with metastatic breast cancer (MBC) treated with first-line bevacizumab (TRANSBREAST): Preliminary results.

J. Rifa

Papers

Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis: Comparison with the main clinical and pathological prognostic factors

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis

Tumor markers (CEA, CA 125, CYFRA 21.1, SCC and NSE) in non small cell lung cancer (NSCLC) patients as an aid in histological diagnosis and prognosis: Comparison with the main clinical and pathological prognostic factors

Multicentric, observational, transversal study to describe the clinical profile of patients with metastatic breast cancer (MBC) treated with first-line bevacizumab (TRANSBREAST): Preliminary results.

Factors influencing survival in a prospective cohort of patients with non-small cell lung cancer: an updated assessment.