Washington, January 20 (ANI): While a clinical trial was halted early following the observation that patients using a cream comprising a commonly used acne drug called tretinoin seemed more likely to die than those using a placebo, evidence does not show that the excess deaths were caused by the therapy.
"The potential of retinoid compounds to prevent cutaneous malignant lesions (skin cancers) has been of considerable interest, and some are effective for this purpose," the authors write as background information in the research article, published in the Archives of Dermatology, one of the JAMA/Archives journals.
They add that the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial was launched in 1998 to assess whether high-dose therapy with a cream containing one such retinoid, tretinoin, could prevent cancer.
During the study, 1,131 veterans - 97 per cent men, average age 71 - were randomly assigned to apply either a cream containing 0.1 per cent tretinoin or an unmedicated cream daily to their face and ears. They were then examined by a dermatologist every six months, with a planned study end date of Nov. 15, 2004.
The article further highlights the fact that a report prepared for one of the study's several oversight committees in 2004 identified a statistically significant increase in the number of deaths among study participants in the group using tretinoin, and the trial was consequently halted six months early, in May 2004.
Dr. Martin A. Weinstock, of the VA Medical Center and Brown University, Providence, R.I., and colleagues assessed the data collected during the study to assess the relation of the medication to death risk.
The researchers identified study participants who had died and gather more information about cause of death, including accessing the VA master death file.
With the aid of the records and original study data, the researchers identified 108 patients in the tretinoin group and 76 in the control group, who had died before the end of the intervention period, and an additional 14 in each group who had died before the end of the study period (November 2004).
After considering other factors that might increase the risk of death-such as smoking, age and co-occurring illnesses-there was still a significantly higher risk of death in the treatment group.
The researchers, however, insisted that additional analyses appeared to show that tretinoin was not the cause of death, as there was no clear association between the number of tubes of cream used and death, and there was no consistency in the causes of death among participants.
However, in the treatment group, 15 patients died of non-small cell lung cancer, 12 of vascular disorders, and 15 of respiratory and other chest disorders-causes associated with smoking, which some previous studies have suggested interacts with compounds in some ways similar to tretinoin, but administered systemically, to produce additional health risks.
The researchers said that the participants were asked whether they smoked, but their smoking status was not verified, which potentially affected the detected associations.
"The biological implausibility, lack of specificity of causes of death, inconsistency with previous experience, weakness of other supportive evidence in our data and weak statistical signal cast doubt on a potential causal association of topical tretinoin with death in the VATTC Trial," the authors write.
"We do not conclude that this trial provides appropriate grounds for hesitating to use topical tretinoin in clinical practice in the absence of additional evidence," they add. (ANI)