Vitamin A and retinoid derivatives for lung cancer: a systematic review and meta analysis.

Heidi Fritz,Andrew Seely,Kieran Cooley,Raimond Wong,Stephen Sagar,Dean Fergusson,Deborah Kennedy,Rochelle Fernandes,Dugald Seely,Steve Doucette,John D Minna

doi:10.1371/journal.pone.0021107

Heidi Fritz, Andrew Seely + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0021107

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Journal: PloS one	Publication Date: Jun 27, 2011
Citations: 135	License type: CC BY 4.0

Affiliation: Ottawa Hospital Research Institute, McMaster University

Abstract

BackgroundDespite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers.Methods and FindingsTwo independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation- therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13–1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087).ConclusionsThere is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study.

Highlights

Lung cancers account for 12% of cancers globally and are the most common cancer type second only to non-melanoma skin cancer [1]
There is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Summary

Introduction

Lung cancers account for 12% of cancers globally and are the most common cancer type second only to non-melanoma skin cancer [1]. Lung cancers are the leading cause of cancer mortality, with an estimated 159,390 deaths in 2009 in the United States alone [1,2] Because of their prevalence, severity, and lack of effective treatment, it is crucial to find new interventions for the treatment and prevention of this disease. Natural retinoids have been used in the treatment of lung cancers since the late 70’s when the first human trials were conducted [4,5,6,7] on the basis of antiproliferative effects specific to epithelial tissues and tumors [8,9,10,11].

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