The present study is the first randomized, double-blind, placebo-controlled clinical trial evaluating the effectiveness of topical Aloe vera 3% ointment at a dose of 1 g/twice a day in the prevention of ARP in colorectal cancer patients receiving RT. Results from this study show that Aloe vera gel is superior to the placebo in the prevention of the incidence of ARP and related symptoms in some aspects.
Numerous risk factors play an important role in radiation-induced skin damage. Continuous free radical production potentiates the intracellular inflammatory response. The main mechanism of RT-induced proctitis is DNA damage and cell death which trigger the inflammatory responses following exposure to radiation (16). Previous studies indicated that anti-inflammatory agents can decrease the severity of ARP partly by reducing inflammation (17, 18).
It is interesting to note that radiation-induced-mucositis has a similar pathophysiology to that of ARP. In both conditions, oxygen species probably have a significant influence on initiation and progression of inflammatory lesions. Previous studies have demonstrated the healing effects of Aloe vera in radiation-induced oral mucositis by scavenges free radicals. Although the preventive effects of Aloe vera in ARP has not been investigated earlier, this is giving us a clue regarding the beneficial effects of this herbal medicine (18). Different modalities for ARP prevention, including shielding the rectum during radiation, precise dose-planning, new radiation techniques, and medical therapy (i.e., amifostine) have indicated some degrees of improvements in several clinical trials. Clinically significant results with reduction of ARP symptoms, however, have not been achieved with most studies. Thereby, alternative therapeutic options for this bothersome condition are needed (12–15).
Aloe vera contains multiple antioxidant compounds which have anti-inflammatory effects including superoxide dismutase, vitamins C and E, etc. (18). Previous studies showed that Aloe vera has been widely used to treat various conditions such as burn wound, radiation-related dermatitis, mucositis, esophagitis, acne vulgaris, and psoriasis vulgaris but none of them investigated the effect of this dry and warm weather plant in ARP (1, 19–21).
Although the overall primary and secondary outcomes of Aloe group were better than the placebo group, with exception of diarrhea, RTOG total scores and CRP, all measures of clinical presentation toxicity did not achieve a statistically significant difference with Aloe vera ointment, compared to the placebo arm. Results from this study have extended the findings of earlier researches and indicated that Aloe vera was at least beneficial in alleviating the bothersome symptoms of radiation-induced damages (22). Aloe vera has shown promising effects in prevention of radiation-induced dermatitis in breast cancer patients receiving RT, through its anti-inflammatory and anti-oxidant properties, likewise to the results observed in the present study (23).
Quantitative-CRP is a non-specific, highly sensitive, acute-phase reactant because of the pronounced rise in concentration after tissue injury or inflammation (24). DNA damage in ARP can increase inflammatory responses and rise in CRP levels. In this study, quantitative CRP was measured during the course of RT, as a reflection of systemic inflammation. As the results of the present study illustrated, CRP serum levels had a descending trend after the treatment with Aloe vera, which was significantly lower in in comparison to the placebo group (Fig. 4).
The main limitation is the small sample size. It should be pointed out that until now, the efficacy of Aloe vera in ARP prevention in rectal cancer has not been evaluated. Thus, this primary evaluation is the first trial of Aloe vera to gain an insight for future studies. Another limitation was the lack of measurement of chemical constituents of Aloe vera extract that possess antioxidant and anti-inflammatory effects. Although endoscopic evaluation of the rectosigmoid would be advantageous for response assessment, it has yielded inconsistent descriptions of the character of inflammation. Focal erythema, friability, and mechanical damage are commonly noted. This is the first preliminary clinical trial of treatment with Aloe vera and seeks further studies.