Small-cell lung cancer: patients included in clinical trials are not representative of the patient population as a whole.

Unité d'Oncologie Médicale, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Annals of Oncology (Impact Factor: 6.58). 08/1999; 10(7):809-15.
Source: PubMed

ABSTRACT To determine the clinical characteristics of the subpopulation of patients not included in clinical trials, their outcome, and the reasons for their ineligibility and non-participation.
We studied 57 patients (out of 178 consecutive patients with SCLC), who were not included in any of the three successive clinical trials completed at our center during the study period. We also compared 37 patients excluded from the largest clinical trial to their 73 included counterparts.
Reasons for ineligibility (n = 53) included low Karnofsky index (n = 17), advanced age (n = 12), non-feasible long-term follow-up (n = 12), previous history of cancer (n = 8), contraindication for anthracyclines (n = 5), and other medical reasons (n = 11). Only four eligible patients were not included in the trials. As compared to patients included in the studies, non-included patients had a significantly lower Karnofsky index, were older, presented more frequently with metastatic disease, and had a lower response rate to treatment and a shorter survival. However, exclusion from the trial was not an independent prognostic factor by multivariate analysis.
Selection biases were unlikely in the three trials, based on the high ratio of included/eligible patients. However, the subgroup of patients included in the trials was not representative of the patient population as a whole because of restrictive eligibility criteria. Results from published clinical trials to the overall population should be extrapolated only with caution. We suggest that the proportion and major characteristics of ineligible and non-participating patients be mentioned in any publication of a clinical trial.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival.METHODS In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years.RESULTSThe key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%).CONCLUSIONS In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies. Cancer 2000;89:523–33. © 2000 American Cancer Society.
    Cancer 08/2000; 89(3). · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Stakeholders derive many benefits from cancer clinical trials, including guidance for future oncologic treatment decisions. However, whether enrollment in cancer trials also improves patient survival independently of trial outcomes remains underinvestigated. We hypothesized that cancer trial enrollment is not associated with patient survival outcomes. STUDY DESIGN: Using the 2002 to 2008 California Cancer Registry, we identified 555,469 patients with stage I to IV solid organ tumors. Baseline characteristics were compared by trial participation status. Logistic regression determined predictors of trial enrollment. Multivariate Cox proportional hazards regression examined the impact of trial participation on overall and cancer-specific mortality with adjustment for covariates. RESULTS: Only 0.33% of our cohort was enrolled in clinical trials. Trial participants were likely to be younger than 65 (odds ratio [OR] 2.13; 95% CI 1.90 to 2.38), Hispanic rather than non-Hispanic white (OR 0.78; 95% CI 0.67 to 0.90), and have breast cancer (OR 3.14; 95% CI 2.62 to 3.77). Multivariate survival analyses demonstrated that enrollment in cancer trials predicted a lower hazard of death. However, when stratified by disease site, this survival benefit was observed only in lung, colon, and breast cancers. Sensitivity and interaction analyses confirmed these relationships. CONCLUSIONS: In this first population-based study examining trial effect in solid organ cancers, enrollment into cancer trials predicted lower overall and cancer-specific mortality among common cancer sites. Although these findings may demonstrate a survival benefit due to trial enrollment, they likely also reflect the favorable attributes of trial enrollees. Once corroborated, stakeholders must consider broader cancer trial designs representative of the cancer burden treated in the real world.
    Journal of the American College of Surgeons 02/2013; · 4.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, "real-world" patients with respect to presenting characteristics and survival. We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials.
    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor

Full-text (2 Sources)

Available from
Jun 4, 2014