Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

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.

Angiogenesis inhibiting capacity of Basella rubra and Syszygium cumini fruit extracts using chorioallantoic membrane assay

“…Fig. 1 showed the anti-angiogenic activity of each treatment where retinol palmitate(Positive Control) showed the highest activity followed by Pure Lumboy Extract (Treatment 2), and Pure Alugbati Extract (Treatment 1).This anti-angiogenic capacity of retinol palmitate was already reported in the studies of Fritz, et al, (2011) andNagpal &Chandraratna (1996). ANOVA revealed that the number of new-formed blood vessel branches among treatments, a 23.806 F-computed value and .000 probability value was attained.…”

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

“…33,34 Retinol and its derivatives are thought capable of reducing oxidative stress and the risk of carcinogenesis. 35 However, considering the diversity of retinol's cellular activities (including cellular growth, differentiation, proliferation and apoptosis), the lack of convincing inverse associations for other carotenoids or vitamins and the remaining inverse association when adjusting for ROM, it is possible that the association between retinol and CRC is not due to its role as an antioxidant. 4,35 The association between retinol and colon cancer attenuated after exclusion of the case-control sets with a follow-up below 2 years.…”

“…35 However, considering the diversity of retinol's cellular activities (including cellular growth, differentiation, proliferation and apoptosis), the lack of convincing inverse associations for other carotenoids or vitamins and the remaining inverse association when adjusting for ROM, it is possible that the association between retinol and CRC is not due to its role as an antioxidant. 4,35 The association between retinol and colon cancer attenuated after exclusion of the case-control sets with a follow-up below 2 years. This likely indicates a certain degree of reverse causality, possibly caused by the oxidative stress induced by the subclinical cancer as was suggested in the association between ROM and CRC previously within EPIC.…”

Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

“…In particular, the importance of RA is exemplified by its strong cellular differentiation-inducing capability and its utility in the therapy of acute promyelocytic leukemia. [8][9][10] RA also shows anti-proliferative activities against melanoma, 11) prostate cancer, 12,13) lung cancer, 14,15) and breast cancer, 16,17) but not against refractory cancers. None-the less, it is not known whether other forms of vitamin A, such as retinol and REs, in particular retinyl palmitate (RP), exhibit anti-cancer effects.…”