Evidence-Based Statistics on Complete Prevention and Rapid Sustained Elimination of Chemoradiation Mucositis by ProThelial

Background: Of the 1.6 million individuals annually diagnosed with cancer, 522,166 received chemoradation, with 234,975 developing toxic mucositis and 20% dying within 5 years due largely to mucositis-mediated unplanned treatment breaks. In a mucositis registry study¹ of 66 consecutive patients undergoing chemoradiation using 2 different radiation protocols, 5 targeted immuno and 6 nontargeted chemotherapies by 32 oncologists in 24 institutions across 14 states in the United States, ProThelial (polymerized cross-linked sucralfate) was prescribed for prevention in 8 patients and for elimination in 58 patients (48 males, 18 females, aged 14-96 years). All 8 patients treated for prevention, 53 patients treated for reversal, and 5 patients lost to follow-up entered into data analysis. Primary outcomes of patient-reported mouth/throat soreness, and clinician-observed WHO grade mucositis, EROTC/RTOG-oral and GI mucositis were assessed at days 1, 2, 3, and 7 of use of ProThelial and at the close of cancer treatment. All 8 patients scheduled for G-tube and expected to develop mucositis never developed mucositis and did not require G-tube placement. All 53 patients had 2- to 3-day elimination of mucositis sustained throughout treatment as assessed by both primary outcome measures.

Objectives: Grade the significance of the ProThelial data through a statistical analysis of treatment effect compared with historical controls of 351 patients experiencing mucositis duration of 70 to 84 days.^2-4

Methods: Complete a Glasziou rate ratio analysis,⁵ a relative risk analysis, and conduct a type I and type II error analysis by using the observed effect size of ProThelial to determine adequacy of sample size of 66 patients using the P value _.001, powered at 95% confidence of no false negatives.

Results: The Glasziou treatment effect for prevention, rapid reversal, and sustained elimination was 100%, 96%, and 96%, respectively, for ProThelial versus 0% for generic sucralfate and MASCC-supported interventions. The type I and type II error with the ProThelial treatment effect at 0.1%, powered at 95%, predicted that the trial sample size required to verify a ProThelial treatment effect that reduces 70- to 84-day duration to 2 to 3 days was a total of 3 patients. The ProThelial trial had 61 patients with these outcomes versus the 3 that were statistically required. The 70- to 84-day duration of mucositis reduced to 2 to 3 days by ProThelial was a 96% to 97% reduction in mucositis duration, which is unprecedented. Complete prevention of toxic mucositis by ProThelial was equally unprecedented.

Conclusions:

1. Complete prevention and/or rapid and sustained elimination of toxic mucositis
   • Should reduce mucositis-associated costs
   • Should eliminate mucositis-associated morbidity
   • Should eliminate mucositis-associated mortality (an expected 20% 5-year mortality rate)
2. Statistically significant evidence shows that ProThelial is associated with complete prevention and rapid sustained elimination of toxic mucositis during chemoradiation.
3. ProThelial should be used in most patients receiving chemoradiation or undergoing HSCT.

References

1. McCullough RW. A 66 patient multi-institution phase IV post-authorization surveillance of ProThelial (high potency polymerized cross-linked sucralfate) single agent efficacy for the prevention and rapid reversal of chemo-radiation induced oral, esophageal and intestinal mucositis. Brit J Med Medical Res. 2015;10:1-17.
2. Elting LS, Keefe DM, Sonis ST, et al. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008;113:2704-2713.
3. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341-1346.
4. Franco P, Martini S, Di Muzio J, et al. Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer. Med Oncol. 2017;34:81.
5. Glasziou P, Chalmers I, Rawlins M, et al. When are randomised trials unnecessary? Picking signal from noise. BMJ. 2007;334:349-351.