Radiation Oncology/Supportive care/Proctitis

Proctitis Management

Acute radiation proctitis

• Timing: during and within 6 weeks of RT
• Symptoms: diarrhea and rectal urgency or tenesmus, bleeding not as common
• Course: usually resolve within 2-6 months
• No specific therapy required; no prophylactic measures successful

Sucralfate Prophylactic

• Multi-institutional, 2001 (Australia)(1995-1997) PMID 11597802 -- "The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial." (Kneebone A, Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):628-35.)
  • Randomized. 338 patients with localized prostate CA. Randomized to 1) 3g oral sucralfate suspension BID during RT or placebo; balanced but placebo group more liquid baseline stools
  • Outcome: No difference in stool frequency, consistency, flatus, mucus, or pain. More bleeding in sucralfate group (64% vs. 47%, SS)
  • Conclusion: No difference for oral sucralfate

• North Central Cancer Treatment Group, 2000 PMID 10715293 -- "Sucralfate in the prevention of treatment-induced diarrhea in patients receiving pelvic radiation therapy: A North Central Cancer Treatment Group phase III double-blind placebo-controlled trial." (Martenson JA, J Clin Oncol. 2000 Mar;18(6):1239-45.)
  • Randomized. 123 patients, pelvic RT to minimum 45 Gy +/- oral sucralfate 1.5g q6 hours
  • Outcome: fecal incontinence (16% vs. 34%, SS), need for protective clothing (8% vs. 23%, SS) worse with sucralfate, otherwise no difference
  • Conclusion: sucralfate didn't improve bowel toxicity, and may have aggravated some GI symptoms

• TROG, 1997 (Australia) PMID 9424000 -- "A phase III double-blind randomised study of rectal sucralfate suspension in the prevention of acute radiation proctitis." (O'Brien PC, Radiother Oncol. 1997 Nov;45(2):117-23.
  • Randomized. 86 patients with localized prostate CA. Treated with 1) daily 3.0g sucralfate enema in 15 mL suspension vs. 2) suspension alone. RT 64/32. (See below for long-term proctitis results)
  • Outcome: Grade 2 proctitis sucralfate 61% vs. placebo 71% (NS). No difference in time-to-onset or duration, or quality of life
  • Conclusion: Sucralfate enema not helpful in reducing acute radiation proctitis

Misoprostol Prophylactic

• Goettingen, 2005 (Germany) PMID 16137837 -- "A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer." (Hille A, Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1488-93.)
  • Randomized. 100 patients with prostate CA. RT +/- misoprostol suppositories
  • Outcome: No differences in proctitis symptoms, onset, or duration. More rectal bleeding in misoprostol group
  • Conclusion: Misoprostol not helpful

Chronic radiation proctitis

• Chronic Radiation Proctitis
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• Timing: 9-14 months after RT, but sometimes after 2 years (and as late as 30 years)
• Etiology: obliterative endarteritis and chronic mucosal ischemia, leading to progressive epithelial atrophy and fibrosis. Ultimately, development of a chronically ischemic intestine prone to fibrosis and bleeding
• Symptoms: diarrhea, obstructed defecation (if strictures), bleeding, rectal pain, rectal urgency, and fecal incontinence. Rarely fistulas, SBO
• Diagnosis: colonoscopy, barium studies if suspecting strictures and fistulas
• Treatment:
  • Stool softeners - consider if mild obstructive symptoms
  • Dilation - consider if stool softeners not effective in obstructive symptoms
  • Sulfasalazine - disappointing results
  • Sucralfate enema - no benefit in prophylaxis; good response in radiation proctitis
  • Hyperbaric oxygen - some benefit for fecal urgency and bleeding
  • Metronidazole - benefit for bleeding and rectal ulcers
  • Formaldehyde - induction of coagulative necrosis; beneficial for bleeding
  • Endoscopy (Argon plasma coagulation) - benefit for bleeding
  • Surgery - reserved for intractable symptoms

Sucralfate Therapeutic

• Chandigarh, 1991 (India) PMID 1670631 -- "Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate." (Kochhar R, Dig Dis Sci. 1991 Jan;36(1):103-7.)
  • Randomized. 37 patients with RT-induced proctosigmoiditis. Treate with 1) 3.0g oral sulfasalazine x4 weeks + 20 mg BID rectal prednisolone enama vs. 2) 2.0g BID rectal sucralfate enema
  • 4-week outcome: both groups significant clinical and endoscopic improvement; sucralfate enema clinically significantly better clinically, same endoscopically
  • Conclusion: both treatments effective; sucralfate enemas better clinical response and cheaper

Sucralfate Prophylactic

• TROG, 2002 (Australia)(1995-1996) PMID 12243820 -- "Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: longer term follow-up of a phase III trial--Trans-Tasman Radiation Oncology Group. (O'Brien PC, Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):442-9.)
  • Randomized. 86 patients with localized prostate CA. Treated with 1) daily 3.0g sucralfate enema in 15 mL suspension vs. 2) suspension alone. RT 64/32. Median F/U 5 years (see above for acute proctitis results)
  • Outcome: Grade 2 toxicity sucralfate 5% vs. placebo 12% (NS); late rectal bleeding 54% vs. 59% (NS)
  • Conclusion: No benefit

Pentoxifylline

• Royal Marsden; 2008 PMID 18339525 -- "Pentoxifylline to treat radiation proctitis: a small and inconclusive randomised trial." (Venkitaraman R, Clin Oncol (R Coll Radiol). 2008 May;20(4):288-92. Epub 2008 Mar 12.)
  • Randomized. 40 patients. Arm 1) standard treatment vs. Arm 2) pentoxifylline x6 months
  • Outcome: No difference
  • Conclusion: No advantage for prevention of late rectal bleeding with pentoxifylline