Cream containing tretinoin associated with death in clinical trial, but relationship does not appear causal
According to the National Cancer Policy Board, it is estimated that by the year 2050 there will be more cancer survivors in the United States than those newly diagnosed with the disease. That is why researchers at The Cancer Institute of New Jersey (CINJ) are taking a closer look at the specific needs of cancer
Full Post: Cancer survivor needs examined beyond specialized care
Patients using a cream containing tretinoin, a retinoid commonly used to treat acne and other conditions, appeared more likely to die than those using a placebo in a clinical trial that was halted early as a result, according to a report in the January issue of Archives of Dermatology.
However, evidence does not suggest these 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 article. In 1998, the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial was launched to assess whether high-dose therapy with a cream containing one such retinoid, tretinoin, could prevent cancer. A total of 1,131 veterans (97 percent men, average age 71) were randomly assigned to apply either a cream containing 0.1 percent 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.
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. The trial was therefore halted six months early, in May 2004. Martin A. Weinstock, M.D., Ph.D., 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.
Because death was not an end point in the original study, additional efforts were made to identify study participants who had died and gather more information about cause of death, including accessing the VA master death file. Through these records and original study data, researchers identified 108 patients in the tretinoin group and 76 in the control group who died before the end of the intervention period and an additional 14 in each group who died before the end of the study period (November 2004). After considering other factors that might increase the risk of death - including smoking, age and co-occurring illnesses - there was still a significantly higher risk of death in the treatment group.
However, additional analyses did not support tretinoin as a cause of death. For example, there was no clear association between the number of tubes of cream used and death. 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. Participants were asked whether they smoked, but their smoking status was not verified, potentially affecting 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.”
(Arch Dermatol. 2009;145:18-24.
Editorial: Physicians Should Discuss Results With Patients
“Public health ideally uses the precautionary principle - that possible harm should be avoided before harmful effects are unquestionably proven,” write Lisa M. Schilling, M.D., M.S.P.H., and Robert P. Dellavalle, M.D., Ph.D., M.S.P.H, of the Department of Veterans Affairs Medical Center, Denver, in an accompanying editorial.
“At a minimum, this principle should cause prescribing physicians to discuss the results of the VATTC with elderly men using topical tretinoin,” they write. “More circumspect practitioners may wish to discuss the results of the VATTC with all patients using topical tretinoin. This dialogue should include that the results of the VATTC may have been due to chance, but also that the outcome of death was not initially anticipated, and owing to the ad hoc analysis, various important risk factors, such as smoking status, might not have been completely ascertained. These discussions provide an opportunity for all health care providers prescribing tretinoin to emphasize tobacco prevention and cessation with their patients.”
(Arch Dermatol. 2009;145:76.
An analysis of previous studies indicates that smoking is significantly associated with an increased risk for colorectal cancer and death, according to an article in the December 17 issue of JAMA, the Journal of the American Medical Association. Although tobacco was responsible for approximately 5.4 million deaths in 2005, there are still an estimated 1.3
Full Post: Smoking significantly linked to increased risk for colorectal cancer
Participants in clinical trials report being satisfied with personalized, accurate communication of results by study investigators soon after the study findings are released publicly, according to a report in the December issue of Archives of Neurology. Even though volunteers in clinical trials expose themselves to risk, there is no legal mandate for investigators to inform
Full Post: Participants in clinical trials value personalized, accurate information about study results
A study published this month in The New England Journal of Medicine, “Mortality Attributable to Smoking in China,” provides an estimate of the number of premature deaths in China in 2005 that were caused by smoking. The study, carried out by a multinational team led by researchers at Tulane University School of Public Health and
Full Post: Smoking prevention programs badly needed in China
An ointment made from indigo naturalis, a dark blue plant-based powder used in traditional Chinese medicine, appears effective in treating plaque-type psoriasis, according to a report in the November issue of Archives of Dermatology. Psoriasis is a chronic skin disease for which no cure exists, only therapies that bring it into remission, according to background
Full Post: Ointment made from indigo naturalis may help treat psoriasis
Canadian researchers are trying to answer why some smokers develop lung cancer while others remain disease free, despite similar lifestyle changes. Results were presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research. According to the Centers for Disease Control and Prevention, more people die from lung
Full Post: Why only some former smokers develop lung cancer