Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis

Background

Chronic radiation proctitis (rectal inflammation) may develop after the completion of pelvic radiotherapy. Presently there is no recommended standard management.

Objectives

To assess the effects of various non-surgical options for managing late chronic radiation proctitis.

Search strategy

In the first version of this review the following were searched : the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2001) Register 2001; MEDLINE 1966 to 2001; EMBASE 1980 to 2001; CANCERCD 1980 to 2001; Science Citation Index 1991 to 2001; CINAHL 1982 to 2001,and sources of grey literature. We also handsearched textbooks and contacted experts in the field. In the current update the search has been extended to April 2007.

Selection criteria

Studies (preferentially RCTs) of interventions for the non-surgical management of late radiation proctitis in patients who have undergone pelvic radiotherapy for cancer.

Data collection and analysis

Inclusion criteria were independently applied by two review authors (AD and EJM) and any disagreement resolved by involving a third reviewer.

Main results

In the original review there were six RCTs. None compared anti-inflammatories with placebo. However, rectal sucralfate showed greater clinical improvement for proctitis than anti-inflammatories (odds ratio (OR) 14.00, 95% confidence interval (CI) 1.46 to 134.26; n = 1 study) , though no difference was seen for endoscopic improvement (OR 2.74, 95% CI 0.64 to 11.76, n = 1 study). The addition of metronidazole to the anti-inflammatory regime also appeared to improve the response rate, as measured by reduction in rectal bleeding, diarrhoea, erythema and ulceration (n = 1 study). Similarly rectal hydrocortisone appeared to be more effective than rectal betamethasone for clinical improvement although no difference was seen in endoscopic improvement (n = 1 study). Short chain fatty acid enemas did not appear to be effective compared to placebo (n = 2 studies). Comparing the heater probe and bipolar electrocautery (n = 1 study), there was no discernible difference for severe bleeding after one year, but the heater probe demonstrated a greater increase in the haematocrit and reduced transfusion requirements.

The current update has identified a further three RCTs and a phase II study. One of the RCTs (Clarke 2004) examines the effect of hyperbaric oxygen (HBO) versus placebo with significantly improved chance of healing following HBO for radiation proctitis (Relative Risk (RR) 2.7, 95% CI 1.2 to 6.0, P = 0.02, number to needed to treat (NNT) = 3). This RCT was included in the 2005 Cochrane Systematic review (Bennett 2005). Clarke 2004 is quoted as evidence for the benefit of late radiation injury to the pelvis with a significantly improved chance of healing following HBO therapy (HBOT) for radiation proctitis. The other RCT (Ehrenpreis 2005) reports a double-blind placebo RCT of vitamin A for symptomatic chronic radiation proctopathy where vitamin A significantly reduced rectal symptoms perhaps because of wound-healing effects. The third RCT (Kneebone 2005) is a large study where patients were randomised to receive oral sucralfate. This trial demonstrated no statistically significant reduction in the incidence of late rectal toxicity in patients randomised to receive sucralfate. However, this result was considered inconclusive, because the trial was unable to exclude clinically important differences in the late toxicity rates. The phase II series (Veerasarn 2006) is a study of long term follow up data been obtained from patients who have received WF10 therapy. In the phase II study the median follow up was 51 months. No adverse effects were found and there favourable results in terms of control of bleeding from late radiation cystitis and proctitis.

Authors' conclusions

Late radiation complications are relatively rare, involving potential carers and poor diagnostic criteria. Although certain interventions look promising (e.g. rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies, even if well conducted provide insufficient evidence. The episodic and variable nature of late radiation proctitis requires large multi-centre placebo-RCTs to establish whether particular treatments are effective.

Regional or centralised registers of radiation toxicity should be established so interventions can be administered in the setting of multi-centre RCTs with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data including quality of life (QOL) evaluations.