Successful Treatment of Acute Radiation Proctitis with Aloe Vera : A Preliminary Randomized Controlled Clinical Trial

Abstract

Background:

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area.

Subjects and Interventions:

In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46–72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0–4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home).

Results:

There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for “clinical presentation total” and “RTOG total” were 3.97 (1.3–11.9) and 5.9 (1.6–21.6), respectively.

Conclusion:

A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

Introduction

Radiation therapy is an accepted method in the treatment of pelvic malignant diseases. Pelvic radiotherapy may result in undesirable adverse effects, whereas acute radiation proctitis (ARP) is the most common one. ARP can develop during or shortly after a course of radiation therapy. It presents as diarrhea, rectal bleeding, pain, abdominal cramping, mucoid discharge, and fecal urgency and is usually temporary.^1,2 However, it may have a significant negative impact on daily activities of the patients.

A variety of treatment agents have been investigated for treatment of radiation-induced proctitis, such as anti-inflammatory agents,³ topical steroid solutions,⁴ bipolar electrocoagulation,⁵ hyperbaric oxygen,⁶ laser application,⁷ formalin-soaked gauze,^8,9 and short-chain fatty acid enema¹⁰; however, unfortunately, there is no widely accepted prophylactic or effective treatment for radiation proctitis.

The molecular mechanism of ARP involves reactive oxygen metabolites and is believed to be a result of oxidative stress,¹¹ though the exact mechanism is unknown. Aloe vera has been known as a traditional folklore medicine for the treatment of a range of diseases, including accelerating the wound healing and treatment of burn injuries in both experimental and clinical studies, and also mucositis induced by radiation or chemotherapy.^12

–16 Some suggest that its effectiveness in treating wounds and burns and in reducing inflammation is mediated through inhibition of cyclooxygenase,¹⁷ but the exact mechanism of action is not fully recognized. So, because of mentioned pathophysiology of radiation-induced proctitis and also antioxidant and anti-inflammatory properties of Aloe vera, we hypothesized that it may be beneficial in the treatment of radiation proctitis too.

The aim of the present study was to determine whether Aloe vera ointment is beneficial in the treatment of ARP. This is the first randomized study of Aloe vera for treatment of proctitis in patients undergoing pelvis radiotherapy. In addition to elimination of proctitis symptoms as our primary endpoint, we evaluated secondary endpoints, including quality of life (QOL) and psychosocial status, by using Hospital Anxiety-Depression (HAD) Scale.

Methods

Ethics considerations, setting, and patients

This study was a randomized, double-blind, prospective, placebo-controlled trial comparing Aloe vera with placebo ointment. After obtaining approval from the Ethical Committee of Mazandaran University of Medical Sciences (Ethics Code: IR.MAZUMS.REC.94–1196), the study proposal was submitted, approved, and registered by the Iranian Registry of Clinical Trials (IRCT) with a registry code of RCT201606042027N6. This clinical trial was carried out in the radiotherapy department of Imam Hospital, a referral center affiliated to Mazandaran University of Medical Sciences (Sari, Iran). All patients who were enrolled in the study were 18 years or more and underwent irradiation for pelvic cancers.

Exclusion criteria were evidence of active infection, evidence of other sources of hematochezia including colon cancer, inflammatory bowel disease, hemorrhoids, anal incontinence, anorectal fistula, anorectal stenosis, previous rectal surgery, pregnancy or breast feeding, females of child-bearing age not taking adequate contraception, known allergy to any ingredients of the ointments, and concomitant use of antibiotics or steroids.

Preparation and formulation of Aloe vera ointment

We applied pure spray-dried Aloe vera powder (Giah salamat nasim faraz, Shiraz, Iran). This product consists of the inner gel from the plant.

First, the powder product was analyzed for microbial contaminants. Since the culture results were positive and because of the lyophilized nature of the Aloe product, it was sterilized with gamma waves by Atomic Energy Organization of Iran.

To formulate the ointment, first, 9 g of Aloe vera powder was ground with a mortar to a very fine powder. Next, the yielded powder was levigated with 7 g of liquid white paraffin. Then, the mixture was intimately blended with 284 g of vaseline by the geometric method.

Afterward, the whole mass was passed through a triple-roller ointment mill ointment grinding machine (D-63150; Erweka, Heusenstamm, Germany) to get smooth and super fine blending ointment. Finally, the Aloe vera ointment was filled in similar lacquered aluminum collapsible tubes under laminar flow hood to provide an aseptic environment and to ensure a sterile condition. Each tube weighed 50 g. The ointment contained Aloe vera gel powder 3%. A six-digit random code was labeled on each tube. Our experimental research and formulations were carried out under sterile conditions.

Patients and study procedure

During the period of October 2015 to November 2016, 89 patients completed a cycle of external-beam radiation therapy to the pelvis (46–72 Gy) for pelvis malignancies. Enrolled in the study were 20 patients (13 male and 7 female, with a median age of 57.55 years old) who were presenting ARP syndrome during their radiation therapy. Patients were randomly allocated by random number table, and a similar lacquered aluminum collapsible tube containing Aloe vera or placebo was delivered to each patient. For ethical reasons, all patients with ARP received sulfasalazine 500 mg four times a day (QID) to ameliorate ARP symptoms, though this is not a very well accepted treatment for ARP¹ (Fig. 1). The diagnosis of radiation proctitis was defined as the occurrence of loose stools and tenesmus lasting more than 7 days, associated with at least two of the following symptoms: greater than four bowel movements per day, rectal bleeding, fecal urgency, and abdominal/rectal pain.¹⁸

FIG. 1.

Flow diagram of the study.

The symptoms of ARP were observed in 20 patients: 11 belonging to the placebo arm and 9 to the Aloe group, respectively. Patient age ranged from 24 to 84 years. Every week, patients received five daily fractions of 1.8–2 Gy, a total dose of 50–72 Gy, with a four-field box centered on the pelvis. Patients were instructed to use ointment rectally (Aloe or placebo) for 4 weeks, 1 g twice daily.

The ointment lacquered aluminum collapsible tubes looked identical. The patients, the radiotherapist, healthcare providers, and the investigator of clinical responses were all blinded to the arms of the study. Also, all data were gathered by a single investigator. Patients were assessed a day before and then weekly during radiotherapy for 4 weeks. Compliance was assessed by asking the patients to bring the remainder ointment tubes for weekly visits.

Questionnaires on demographic and clinical details of each patient, including cancer diagnosis, co-morbidity, previous treatments, and the radiation dose, were filled out by the investigator. The clinical activity of ARP was assessed by recording bowel movements/stool consistency, rectal bleeding, abdominal/rectal pain, fecal urgency, and from a self-rating based on the impact of symptoms on life activities. For each factor, a scale from 0 (not present) to 4 (causing significant discomfort) was used. The maximum overall score was 16, and the minimum score required for enrolment was 4 (a score of at least 2 from two discrete symptoms mentioned earlier, concurrently). All our 20 patients completed the study. Clinical presentation score total was calculated by the sum of four specific symptoms (e.g., bowel movements/stool consistency, rectal bleeding, abdominal/rectal pain, fecal urgency).

Radiation-induced toxicity was evaluated weekly by using the Radiation Therapy Oncology Group (RTOG) criteria (Table 1)¹⁹ and based on the clinical presentation (Table 2).¹¹

Table 1.

Baseline and Laboratory Characteristics of Patients

Characteristics	Aloe (n = 9)	Placebo (n = 11)	p
Age, mean ± SD (absolute range), y	55.7 ± 15.4	58.7 ± 15.9	0.68
Male sex, N (%)	5 (55.6)	8 (72.7)	0.6
BMI, mean (SD), kg/m²	24.3 ± 3.2	25.3 ± 2.8	0.49
Dose of radiotherapy in each session, cGy	186.6 ± 10	189.4 ± 10.1	0.54
Total dose of radiotherapy received, cGy	5031.1 ± 17.6	5392.7 ± 859.5	0.19
Concomitant medication, N (%)
NSAIDs	1 (11.1)	1 (9.1)	0.71
Opioid	0 (0)	1 (9.1)	0.55
Anticholinergic	0 (0)	2 (18.2)	0.29
Alpha blocker	1 (11.1)	1 (9.1)	0.71
Condition, N (%)
HTN	1 (11.1)	1 (9.1)	0.88
Diabetes	0 (0)	3 (27.3)	0.22
Dyslipidemia	1 (11.1)	2 (18.2)	0.58
Pelvic surgery	4 (44.4)	4 (36.4)	0.53

BMI, body mass index; HTN, hypertension; NSAIDs, non-steroidal, anti-inflammatory drugs; SD, standard deviation.

Table 2.

Radiation Therapy Oncology Group Criteria

Symptoms	Grade
Diarrhea	0	No symptoms
	1	Minor symptoms requiring no treatment
Proctitis	2	Symptoms that respond to simple outpatient management, and do not affect lifestyle
	3	Distressing symptoms affecting lifestyle; may necessitate hospital admission or minor surgical intervention (e.g., urethral dilation)
Cystitis	4	Major surgical intervention or long stay in the hospital necessary (e.g., laparotomy, colostomy, or cystectomy)
	5	Fatal complications

The impact of these symptoms was also graded by using a questionnaire regarding the effect of these symptoms on lifestyle (Table 3).¹¹

Table 3.

Radiation Proctitis Symptom Score

	Score
Symptoms	0	1	2	3	4
Bleeding	Not present	Minor symptoms not requiring medications	Moderate disturbing symptoms alleviated by analgesic or anticholinergic medication	Significant symptoms with bowel movement	Significant discomfort on rest or symptoms requiring hospitalization
Diarrhea
Fecal urgency
Abdominal/rectal pain

Possible score range: 0–16.

We appraised the psychosocial status of the patients by applying HAD Scale.²⁰ The patients were requested to weekly fill out the HAD form considering their feelings during the past week.

Calculation of sample size and randomization

According to the pilot study, the minimum expected difference between mean values of the total clinical presentation score before and after Aloe vera consumption was considered as 3 score; and also, a standard deviation (SD) of 2 score was expected for the calculation of sample size. Power was set as 80% for the calculation of sample size. With an allowance of 10% lost to follow-up rate, we allocated 11 people to the control group and 9 people to the treatment group.

The patients who met the eligibility criteria were assigned into one of the intervention groups, by using a permuted block randomization method. Blocks of four were used for this purpose. Each ointment was given a six-digit number by the principal investigator. The patients, the treatment team, and the investigator of clinical responses did not know the types of the interventions. At the end of the study, the principal investigator decoded the consumed ointment numbers and assigned each to the appropriate group correctly.

Statistical analyses

Qualitative variables were reported by frequency and percent, and quantitative variables were reported by Mean ± SD. Chi-square test and Fisher's Exact Test were used to compare the qualitative variables in the two groups of the study. To analyze the quantitative variables, Mann–Whitney Test was used. A generalized linear model with a repeated-measures test was used for time-trend assessment and time-intervention interaction. For estimating the odds ratio between groups, logistic regression was used. All statistical analysis was conducted by using SSPS software version 19, and differences with a value of p < 0.05 were considered significant.

Results

Participants

The flowchart of enrollment of the patients is displayed in Figure 1. Demographic and baseline clinical characteristics of patients are presented in Table 4. As indicated, there was no significant difference between the two groups in demographic and clinical characteristics (age, gender ratio, body–mass index, total dose and dose of radiotherapy in each session, concomitant medication, and comorbidities).

Table 4.

Quality of Life

	Grade
Symptoms	0	1	2	3	4
	Symptoms cause no effect on daily activity	Symptoms cause inconveniences at least once a week	Symptoms interfere with day-to-day activities more than once a week	Symptoms interfere with routine activities on a daily basis	Afraid to leave home with significant restriction in social life

Possible grade range: 0–4.

Effect of Aloe vera rectal ointment on symptoms

All patients treated with Aloe vera became symptom free or improved greatly as clinical presentation score total decreased from 4.3 (standard error of the mean [SEM]: 2.2) at baseline to 1.2 (SEM: 0.8) at week 4 of treatment. In the placebo group, the overall score value remained almost unchanged (clinical presentation score total changed from 4.2 [SEM: 1.2] at baseline to 3.5 [SEM: 1.1] at week 4). The RTOG score of patients in the Aloe group followed a decline trend (score from 2.89 [SEM: 2.1] to 0.89 [SEM: 1.0]) within the treatment period. None of the symptoms increased during the 4 weeks of follow-up in the Aloe group. The differences between the mean in the two groups were statistically significant for both clinical presentation score total (p = 0.0087) and RTOG total (p = 0.0016).

With the exception of hemorrhage and abdominal/rectal pain (which did not achieve statistical significance, but still favored the Aloe group), all measures of clinical presentation toxicity were better by treatment with Aloe. The toxicity prevented most effectively was diarrhea (p = 0.008) (Table 5). Figures 2 and 3 show the outcomes by applying the Aloe or placebo ointments over the 4 weeks of the study.

FIG. 2.

Hemorrhage trend of changes during 4 weeks of follow-up (a), abdominal/rectal pain trend of changes (b), diarrhea trend of changes (c), fecal urgency trend of changes (d).

FIG. 3.

Cystitis trend of changes during 4 weeks of follow-up (a), proctitis trend of changes (b), RTOG total trend of changes (c), clinical presentation total trend of changes (d). RTOG, Radiation Therapy Oncology Group.

Table 5.

Change Trends of Clinical Presentation in the Two Groups During Follow-Up

	Time				p
Variable	Week 1	Week 2	Week 3	Week 4	Time effect	Group effect	Time × group effect (interaction)
Hemorrhage
Aloe	0.89 ± 0.9	0.55 ± 0.5	0.33 ± 0.5	0.22 ± 0.4	0.007	0.044	0.56
Placebo	0.64 ± 0.8	0.82 ± 0.7	0.64 ± 0.7	0.55 ± 0.5
Abdominal/rectal pain
Aloe	1.89 ± 0.9	1.44 ± 0.7	1 ± 0.7	0.78 ± 0.7	0.0001	0.005	0.93
Placebo	1.27 ± 0.8	1.36 ± 0.7	1.27 ± 0.8	1.09 ± 0.7
Diarrhea
Aloe	0.67 ± 0.9	0.44 ± 0.7	0.33 ± 0.5	0.11 ± 0.3	0.04	0.56	0.008
Placebo	1.3 ± 0.8	1.3 ± 0.8	1.4 ± 0.8	1 ± 0.8
Fecal urgency
Aloe	0.89 ± 0.8	0.44 ± 0.5	0.11 ± 0.3	0.11 ± 0.3	0.014	0.147	0.027
Placebo	1 ± 0.8	1 ± 0.8	0.91 ± 0.7	0.82 ± 0.7
Clinical presentation total
Aloe	4.33 ± 2.2	2.89 ± 1.8	1.78 ± 1.2	1.22 ± 0.8	0.000	0.000	0.0087
Placebo	4.18 ± 1.1	4.64 ± 1.2	4.09 ± 1.6	3.45 ± 1.1
Proctitis
Aloe	1.78 ± 1.4	1 ± 0.9	0.44 ± 0.5	0.33 ± 0.5	0.00009	0.0058	0.094
Placebo	1.64 ± 0.9	1.82 ± 1.2	1.54 ± 1.3	1.36 ± 0.9
Cystitis
Aloe	0.44 ± 0.5	0.22 ± 0.4	0.33 ± 0.5	0.44 ± 0.5	0.704	0.308	0.15
Placebo	0.64 ± 0.7	0.82 ± 0.7	0.73 ± 0.8	0.82 ± 0.7
RTOG total
Aloe	2.89 ± 2.1	1.67 ± 1.6	1.11 ± 0.9	0.89 ± 1.0	0.0008	0.021	0.0016
Placebo	3.64 ± 1.4	4 ± 1.3	3.64 ± 1.6	3.09 ± 1.3

RTOG, Radiation Therapy Oncology Group.

The advantages of Aloe over placebo were statistically marked, especially for clinical presentation total and RTOG total with the odds ratios of 3.97 and 5.9, respectively (Table 6).

Table 6.

Advantage of Aloe Vera over Placebo in the Treatment of Acute Radiation Proctitis

	Odds ratio (95% CI)	p
Hemorrhage	2.1 (0.76–5.5)	0.15
Abdominal/rectal pain	1.5 (0.5–4.2)	0.44
Diarrhea	4.6 (1.3–15.8)	0.015
Fecal urgency	3.1 (0.9–10.3)	0.06
Cystitis	1.5 (0.6–3.6)	0.39
Proctitis	3 (1.07–8.4)	0.037
Clinical presentation total	3.97 (1.3–11.9)	0.014
RTOG total	5.9 (1.6–21.6)	0.007

Data refer to the first 4 weeks of treatment.

CI, confidence interval; OR, odds ratio.

Compliance was good as assessed by comparing the actual and estimated volumes of residual ointment. The Aloe vera ointment was generally well tolerated, and no adverse effects were experienced by any patient in either group.

Hemorrhage and abdominal/rectal pain trend

As shown in Table 5, there was a statistically significant time effect (within-subject differences), indicating that when the two groups were combined, the average hemorrhage and abdominal/rectal pain at baseline was higher than the average after starting the treatment (p = 0.007 and 0.0001, respectively). Furthermore, the trend of changes between groups (between-subject differences or group effects) was also significant (p = 0.044 and 0.005, respectively). But, there was no significant group-by-time interaction effect (p = 0.56 and 0.93, respectively) (Fig. 2).

Diarrhea and fecal urgency trend

Table 5 displays that there were no statistically significant between-subject differences, or group effects (p = 0.56 and 0.147, respectively) for diarrhea and fecal urgency. However, both time effects (p = 0.04 and 0.014, respectively) and group-by-time interaction effects were statistically significant (p = 0.008 and 0.027, respectively).

The average scores of diarrhea in the Aloe group significantly decreased from 0.67 ± 0.9 to 0.11 ± 0.3 over the 4 weeks of the study, and an almost complete cessation of rectal bleeding was observed at the end of week 4. In the placebo group, it remained unchanged, from 1.3 ± 0.8 at week 1 to 1 ± 0.8 at the end of week 4.

The average scores of fecal urgency followed a downward trend during the study, decreasing from 0.89 ± 0.8 in week 1 to 0.11 ± 0.3 at the end of week 4. However, that of the placebo group was again almost unchanged (Fig. 2).

Proctitis and cystitis trend

As illustrated in Table 5, there was a statistically significant time effect (p = 0.00009), indicating that when the two groups were combined, the average proctitis at baseline was higher than the average after the treatment. The trends of changes between groups were also statistically significant (p = 0.0058). Nevertheless, group-by-time interaction effects were not significant (p = 0.094) (Fig. 3).

In terms of cystitis, there were no statistically significant time effects (p = 0.704), group effects (p = 0.308), or group-by-time interaction effects (p = 0.15) (Table 5 and Fig. 3).

Clinical presentation total and RTOG total trend

As demonstrated in Table 5, the average clinical presentation total and RTOG total in the Aloe group were lower than the placebo group after initiating therapy with rectal ointment. The average scores of total clinical manifestations and RTOG total over time significantly decreased by 3.11 ± 1.42 and 2.0 ± 1, respectively, over the 4 weeks of treatment. Again, the trend of changes almost remained unchanged for the placebo group (Fig. 3).

Secondary endpoints

Lifestyle was affected in 14 out of 20 (70%) patients at baseline, and they had multiple symptoms that interfered with their daily lives. The median lifestyle score improved significantly after the treatment with Aloe vera, ranging from 1.1 (SEM: 1.1) to 0.33 (SEM: 0.5). In the placebo group, the overall score value remained almost unchanged (1.8 [SEM: 0.8] to 1.4 [SEM: 0.8]; p = 0.004).

However, treatment with Aloe vera did not influence the psychosocial status of the patients, as there was no statistically significant difference between HAD Scale during the treatment period (p = 0.14 for depression and p = 0.52 for anxiety).

Discussion

This preliminary double-blind placebo-controlled, clinical trial shows very encouraging early results, indicating that topical Aloe vera 3% at a dose of 1 g/day is effective in ARP. Overall subjective clinical scores improved as determined by the clinical presentation and RTOG scores, with subscore analysis showing most improvement in the severity and frequency of fecal urgency and diarrhea, which were significantly reduced in the Aloe group compared with the placebo. Fewer incidences of adverse effects of radiotherapy obviously enhance the QOL of the patients during therapy, as the patients in Aloe group experienced an improved QOL.

In this study, treatment with the safe and widely available medical plant, Aloe vera, appeared to ameliorate the symptoms of diarrhea, fecal urgency and also to significantly improve the patients' lifestyle. This traditional folklore medicine implements its effectiveness in treating wounds and burns and in reducing inflammation through inhibition of cyclooxygenase and scavenging reactive oxygen metabolites.^17,21,22

No proven effective pharmacotherapy is, at present, available for ARP. However, the traditional approach to the treatment of ARP has been directed toward decreasing the inflammation observed in irradiated rectal tissue with the use of anti-inflammatory agents such as amino salicylic acid derivatives,^23,24 and corticosteroids.^4,24,25 Some other agents, including mesalamine, pentoxifylline,²⁶ metronidazole,²⁷ butyrate,¹⁸ and sucralfate,²⁸ have been applied as well. Also, a variety of approaches such as short-chain fatty acid enemas,¹⁰ rectal instillations of formalin,^8,9 endoscopic (laser) therapy,⁷ hyperbaric oxygen,⁶ and Argon plasma coagulation²⁹ have been tried in a limited number of patients. But the responses to such treatment have been disappointing in some cases or have been complicated with ulcerations created in ischemic tissue that may take months to heal. Therefore, the optimal method of safe and effective therapy remains unclear.

Our findings demonstrate a step toward the treatment of radiation-induced proctitis targeting the possible pathophysiology of injury. Although the exact mechanism of action is not clearly recognized, reactive oxygen species may be formed as the direct effect of the radiation itself or the subsequent ischemia induced by the radiation.¹¹ Previous studies suggested a beneficial role for antioxidants in radiation proctitis.³⁰ Therefore, Aloe vera, with antioxidant and anti-inflammatory properties, enhances healing of mucosal lesions and reduces related symptoms. So, it is beneficial in the underlying mechanism of action of the damage to irradiated rectal tissue.

Study limitations

The major limitation of the study is the small number of patients. Although the results of this preliminary study are very promising, and it was performed in a randomized controlled prospective manner with predefined endpoints, these findings need to be confirmed in a larger group of patients with ARP. It should be noted that Aloe vera has not been applied in the treatment of radiation proctitis earlier and we aimed at having a primary evaluation of the tolerability and response of ARP to Aloe vera for the first time. Furthermore, the optimal period of treatment with Aloe vera ointment for a successful treatment outcome of ARP remains unknown as this is the first preliminary clinical trial of treatment with Aloe vera and seeks further studies. Finally, when considering the mechanisms of action by which Aloe yields its efficacy, rectosigmoidoscopic assessment would be advantageous. However, any mechanical intervention during the acute phase should be avoided as it could worsen the condition, due to the risk of irreversible damage to the internal sphincter and the resultant incontinence and infection.³¹ Therefore, we did not find it ethical for the first clinical trial of this herbal medicine.

Conclusion

In summary, the data of this study support that Aloe vera ointment is a safe and effective therapy for ARP. Aloe vera improves the symptoms of proctitis, including diarrhea and fecal urgency scores, and also enhances the QOL of patients without any significant adverse event.

Footnotes

Acknowledgments

The authors gratefully acknowledge the vice chancellor of Research and Technology Affairs of Mazandaran University of Medical Sciences for financial support. The results of this trial are a part of a postgraduate thesis (A.S.).

Author Disclosure Statement

No competing financial interests exist.

References

Denton

, et al. Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer, 2002; 87:134–143.

Schultheiss

, et al. Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys, 1997; 37:3–11.

Szepesi

, et al. Treatment of radiogenic colitis with a rectal foam containing cortisol. Clinical and pharmacologic data. Strahlenther Onkol, 1990; 166:271–274.

Fischer

, et al. Late progress of radiation-induced proctitis. Acta Chir Scand, 1989; 156:801–805.

Jensen

, et al. A randomized prospective study of endoscopic bipolar electrocoagulation and heater probe treatment of chronic rectal bleeding from radiation telangiectasia. Gastrointest Endosc, 1997; 45:20–25.

Clarke

, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: A randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys, 2008; 72:134.e15–143.e15.

Silva

, et al. Argon plasma coagulation therapy for hemorrhagic radiation proctosigmoiditis. Gastrointest Endosc, 1999; 50:221–224.

de Parades

, et al. Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis—An effective but not risk-free procedure: A prospective study of 33 patients. Dis Colon Rectum, 2005; 48:1535–1541.

Tsujinaka

, et al. Formalin instillation for hemorrhagic radiation proctitis. Surg Innov, 2005; 12:123–128.

10.

Talley

, et al. Short-chain fatty acids in the treatment of radiation proctitis. Dis Colon Rectum, 1997; 40:1046–1050.

11.

Kennedy

, et al. Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C. Am J Gastroenterol, 2001; 96:1080–1084.

12.

Maenthaisong

, et al. The efficacy of aloe vera used for burn wound healing: A systematic review. Burns, 2007; 33:713–718.

13.

Langmead

, Makins

, Rampton

. Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro. Aliment Pharmacol Ther, 2004; 19:521–527.

14.

Eshghi

, et al. Effects of Aloe vera cream on posthemorrhoidectomy pain and wound healing: Results of a randomized, blind, placebo-control study. J Altern Complement Med, 2010; 16:647–650.

15.

Khorasani

, et al. Aloe versus silver sulfadiazine creams for second-degree burns: A randomized controlled study. Surg Today, 2009; 39:587–591.

16.

Aghamohamamdi

, Hosseinimehr

. Natural products for management of oral mucositis induced by radiotherapy and chemotherapy. Integr Cancer Ther, 2016; 15:60–68.

17.

Yagi

, et al. Radical scavenging glycoprotein inhibiting cyclooxygenase-2 and thromboxane A2 synthase from aloe vera gel. Planta Med, 2003; 69:269–271.

18.

Vernia

, et al. Topical butyrate for acute radiation proctitis: Randomised, crossover trial. Lancet, 2000; 356:1232–1235.

19.

Rubin

. Special issue: Late effects of normal tissues consensus conference, including RTOG/EORTC SOMA scales. Int J Radiat Oncol Biol Phys, 1995; 31:1035–1360.

20.

Zigmond

, Snaith

. The hospital anxiety and depression scale. Acta Psychiatr Scand, 1983; 67:361–370.

21.

, Xu

, Hu

. Evaluation of antioxidant potential of Aloe vera (Aloe barbadensis Miller) extracts. J Agric Food Chem, 2003; 51:7788–7791.

22.

Yagi

, et al. Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera. Planta Med, 2002; 68:957–960.

23.

Baum

, Biddle

, Miner

. Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis. Dig Dis Sci, 1989; 34:758–760.

24.

Jahraus

, et al. Prevention of acute radiation-induced proctosigmoiditis by balsalazide: A randomized, double-blind, placebo controlled trial in prostate cancer patients. Int J Radiat Oncol Biol Phys, 2005; 63:1483–1487.

25.

Babb

. Radiation proctitis: A review. Am J Gastroenterol, 1996; 91:1309–1311.

26.

Venkitaraman

, et al. Pentoxifylline to treat radiation proctitis: A small and inconclusive randomised trial. Clin Oncol, 2008; 20:288–292.

27.

Cavciæ

, et al. Metronidazole in the treatment of chronic radiation proctitis: Clinical trial. Croat Med J, 2000; 4:314–318.

28.

Hovdenak

, Sørbye

, Dahl

. Sucralfate does not ameliorate acute radiation proctitis: Randomised study and meta-analysis. Clin Oncol, 2005; 17:485–491.

29.

Dees

, Meijssen

, Kuipers

. Argon plasma coagulation for radiation proctitis. Scand J Gastroenterol, 2006; 41(Suppl. 243):175–178.

30.

Petkau

. Role of superoxide dismutase in modification of radiation injury. Br J Cancer Suppl, 1987; 8:87.

31.

Henriksson

, Franzen

, Littbrand

. Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer. J Clin Oncol, 1992; 10:969–975.