Analysis of Lung Cancer Patients Enrolled in CTEP (Cancer Therapy Evaluation Program)-Sponsored Phase I Trials
Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA. Clinical Lung Cancer
(Impact Factor: 3.1).
07/2011; 12(4):218-23. DOI: 10.1016/j.cllc.2011.03.022
A recent review of phase I trials suggests that participation in these trials can be associated with clinical benefit and the rate of drug-related deaths is low. We conducted an analysis of the Cancer Therapy Evaluation Program (CTEP)-sponsored phase I trials to assess the outcomes of lung cancer patients enrolled in phase I trials.
Data from all CTEP-sponsored adult phase I trials conducted between 1997 and 2008 were analyzed. An analysis of demographics, rates of toxicities, and clinical benefit rate among patients with non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and other cancers was conducted.
Of the 3560 patients enrolled in 136 phase I trials, 301 (8.5%) had NSCLC and 40 (1.1%) had SCLC. The median age of lung cancer patients, at 60 years, was significantly higher than patients with other cancers. The rest of the demographics were similar among the groups. The rate of Grade 3-5 toxicities was higher among NSCLC patients (54% versus 46%). The toxicity-related death rate was ≤ 1% among all groups. The clinical benefit rate and median duration in study of approximately 2 months were similar among all groups of patients.
An analysis of the CTEP-sponsored phase I trials shows that lung cancer patients enrolled in these trials have a similar incidence of toxicity-related deaths and a similar probability of clinical benefit as patients with other cancers. These data suggest that patients with progressive lung cancer following approved therapies should be considered for phase I trials.
Available from: Jeremiah A Hayanga
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ABSTRACT: OBJECTIVE To examine the relationship between race and lung cancer mortality and the effect of residential segregation in the United States. DESIGN A retrospective, population-based study using data obtained from the 2009 Area Resource File and Surveillance, Epidemiology and End Results program. SETTING Each county in the United States. PATIENTS Black and white populations per US county. MAIN OUTCOME MEASURES A generalized linear model with a Poisson distribution and log link was used to examine the association between residential segregation and lung cancer mortality from 2003 to 2007 for black and white populations. Our primary independent variable was the racial index of dissimilarity. The index is a demographic measure that assesses the evenness with which whites and blacks are distributed across census tracts within each county. The score ranges from 0 to 100 in increasing degrees of residential segregation. RESULTS The overall lung cancer mortality rate was higher for blacks than whites (58.9% vs 52.4% per 100 000 population). Each additional level of segregation was associated with a 0.5% increase in lung cancer mortality for blacks (P < .001) and an associated decrease in mortality for whites (P = .002). Adjusted lung cancer mortality rates among blacks were 52.4% and 62.9% per 100 000 population in counties with the least (<40% segregation) and the highest levels of segregation (≥60% segregation), respectively. In contrast, the adjusted lung cancer mortality rates for whites decreased with increasing levels of segregation. CONCLUSION Lung cancer mortality is higher in blacks and highest in blacks living in the most segregated counties, regardless of socioeconomic status.
JAMA SURGERY 01/2013; 148(1):37-42. DOI:10.1001/jamasurgery.2013.408 · 3.94 Impact Factor
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To analyze the clinical features and outcomes of advanced non-small cell lung cancer (NSCLC) patients treated in phase I trials.
Patients and methods:
The clinical characteristics, efficacy and toxicity data of 70 pretreated NSCLC patients enrolled in 17 phase I trials between January 2005 and June 2010 were analyzed at our institution.
The histological types were: adenocarcinoma (79%), squamous cell carcinoma (13%), and others. Patients received a median number of 3 prior lines of treatment before inclusion. 1 complete response (CR), 11 (16%) partial responses (PRs), and 29 (41%) stable diseases (SDs) were observed (according to Response Evaluation Criteria in Solid Tumors (RECIST)). The median overall survival (OS) time was 18 months and the median progression-free survival (PFS) time was 4.1 months. The median PFS of these patients within their prior therapy line before phase I inclusion was 4.3 months. A performance status score of 0 and the number of prior lines of treatment were significant for OS and PFS in multivariate analysis, respectively. Grade 3/4 toxicities were observed in 20 (27%) patients, and there was 1 treatment-related death.
Patients in good general condition and with limited pretreatment derived an improved benefit, suggesting that phase I studies may be a valid option for pretreated NSCLC patients.
Onkologie 06/2013; 36(6):357-62. DOI:10.1159/000351257 · 0.86 Impact Factor
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ABSTRACT: At present, the legendary magic bullet, i.e. a drug with high potency and selectivity towards a specific biological target, shares the spotlight with an emerging and alternative polypharmacology approach. Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. It is generally thought that complex diseases such as cancer and central nervous system diseases may require complex therapeutic approaches. In this respect, a drug that "hits" multiple sensitive nodes belonging to a network of interacting targets offers the potential for higher efficacy, and may limit drawbacks generally arising from the use of a single-target drug or a combination of multiple drugs. In this article, we will compare advantages and disadvantages of multi-target versus combination therapies, discuss potential drug promiscuity arising from off-target effects, comment on drug repurposing, and introduce approaches to the computational design of multi-target drugs.
Journal of Medicinal Chemistry 06/2014; 57(19). DOI:10.1021/jm5006463 · 5.45 Impact Factor
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