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Efficacy of Recombinant Human Keratinocyte Growth Factor (rHuKGF) in Reducing Mucositis in Patients with Hematologic Malignancies Undergoing Autologous Peripheral Blood Progenitor Cell Transplantation (auto-PBPCT) After Radiation-Based Conditioning ? Resu

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 12, 2001

Presenter: R. T. Spielberger
Affiliation: City of Hope National Medical Center, Duarte, CA

Background:

1. TBI/VP16/Cyclophosphamide is the established conditioning regimen for auto-PBPCT and it causes approximaetly 80% of severe oral mucositis.
2. Currently, no standard therapy is available to prevent or reduce severe oral mucositis
3. rHuKGF stimulates epithelial cell proliferation and differentiation, and provides cytoprotection of the GI tract. Rubin et al, 1989
4. Other phase I and phase II studies have also shown the rHuKGF effects in other tumor sites (ie. advanced colorectal cancer)

Materials and Methods:

1. Double-blind, placebo-controlled study
2. All patients received 12 Gy of TBI plus 60 mg/kg etoposide and 75 or 100 mg/kg cyclophosphamide as conditioning treatment before auto-PBPCT
3. Randomization of 129 pts into 3 arms: Placebo (PBO) x 3 doses pre- and post- conditioning regimen, vs. rHuKGF (60ìg/kg/day) x 3 doses pre- and PBO x 3 post- conditioning regimen, vs. rHuKGF x 3 does pre- and post- conditioning regimen.

Results:

1. rHuKGF recipients experienced a significant reduction in the duration of severe oral mucositis: pre/post mean = 4 days vs. PBO mean = 7.7 days ( 35% reduction, p=0.001), and pre only mean = 5days vs. PBO ( 48% reduction, p=0.04).
2. Incidences of WHO Gr III and IV mucositis: PBO 50%, Pre-only 33% and Pre-/Post- 26%.
3. Health related quality of life assessments showed reduced mouth/throat soreness and improvements in mucositis related concerns such as swallowing (pre-only 28%, pre/post 37%) , drinking (32%, 41%), eating (37%, 42%), talking, and sleeping.
4. rHuKGF recipients also experienced less severe mucositis-related sequelae such as IV opioid analgesics use and total parentaeral nutrition.
5. In addition, requirement for IV opiods and total peranteral nutrition, time to ANC and hospital stay are decreased in the rHuKGF recipients.
6. Adverse events: mild to moderate skin and oral erythema with/without edema, and asymptomatic transient increases in serum amylase and lipase occurring more frequetly in rHuKGF recipients (76% and 28%) than in PBO (58% and 23%) recipients.
7. Two pts withdrew from study. One rHuKGF recipient with Gr I skin reaction and one in PBO arm developed a myocardial infarction.
8. No significant differences in the two rHuKGF arms.

Authors' Conclusions

1. rHuKGF effectively reduced the duration of severe (WHO Gr 3-4) oral mucositis.
2. rHuKGF decreased the requirement of IV opiods and total peripheral nutrition.
3. rHuKGF improved quality of life of pateitns with hematologic malignancies undergoing auto-PBPCT following TBI and chemotherapy conditioning.
4. rHuKGF was well tolerated.

Clinical/Scientific Implications:

This study shows Recombinant Human Kerotinocyte Growth Factore (rHuKGF) is effective in reducing the incidence of severe mucositis in association with high dose chemotherapy. There were no significant differences in the effectiveness of rHuKGF when looking at the two regimens used in this study. Further studies should define the optimal dosing of rHuKGF. There should also be future studies evalutating patients receiving combined chemotherapy and radiation therapy, as this is a population at high risk for developing mucositis.