Study objective

To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. DESIGN SETTING/PARTICIPANTS: Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non-small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen).

Interventions

Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up.

Measurements and results

Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date.

Conclusions

Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue.

Background Several cancer therapies have been associated with cardiovascular harm in early-phase clinical trials. However, some cardiovascular harms do not manifest until later-phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry-funded trials (69.2% versus 0.0%; P<0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P<0.001). Conclusions Our findings demonstrate significant under-representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later-phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.