Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers
Ricardo Spielberger, M.D., Patrick Stiff, M.D., William Bensinger, M.D., Teresa Gentile, M.D., Ph.D., Daniel Weisdorf, M.D., Tarun Kewalramani, M.D., Thomas Shea, M.D., Saul Yanovich, M.D., Keith Hansen, M.D., Stephen Noga, M.D., Ph.D., John McCarty, M.D., C. Frederick LeMaistre, M.D., Eric C. Sung, D.D.S., Bruce R. Blazar, M.D., Dieter Elhardt, Ph.D., Mon-Gy Chen, M.S., and Christos Emmanouilides, M.D.
Background Oral mucositis is a complication of intensive chemotherapyand radiotherapy with no effective treatment. We tested theability of palifermin (recombinant human keratinocyte growthfactor) to decrease oral mucosal injury induced by cytotoxictherapy.
Methods This double-blind study compared the effect of paliferminwith that of a placebo on the development of oral mucositisin 212 patients with hematologic cancers; 106 patients receivedpalifermin (60 µg per kilogram of body weight per day)and 106 received a placebo intravenously for three consecutivedays immediately before the initiation of conditioning therapy(fractionated total-body irradiation plus high-dose chemotherapy)and after autologous hematopoietic stem-cell transplantation.Oral mucositis was evaluated daily for 28 days after transplantation.
Results The incidence of oral mucositis of World Health Organization(WHO) grade 3 or 4 was 63 percent in the palifermin group and98 percent in the placebo group (P<0.001). Among patientswith this degree of mucositis, the median duration of mucositiswas 6 days (range, 1 to 22) in the palifermin group and 9 days(range, 1 to 27) in the placebo group. Among all patients, regardlessof the occurrence of mucositis, the median duration of oralmucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) inthe palifermin group and 9 days (range, 0 to 27) in the placebogroup (P<0.001). As compared with placebo, palifermin wasassociated with significant reductions in the incidence of grade4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reportedsoreness of the mouth and throat (area-under-the-curve score,29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P<0.001),the use of opioid analgesics (median, 212 mg of morphine equivalents[range, 0 to 9418] vs. 535 mg of morphine equivalents [range,0 to 9418], P<0.001), and the incidence of use of total parenteralnutrition (31 percent vs. 55 percent, P<0.001). Adverse events,mainly rash, pruritus, erythema, mouth and tongue disorders,and taste alteration, were mild to moderate in severity andwere transient.
Conclusions Palifermin reduced the duration and severity oforal mucositis after intensive chemotherapy and radiotherapyfor hematologic cancers.
Source Information
From the City of Hope National Medical Center, Duarte, Calif. (R.S.); Loyola University Medical Center, Maywood, Ill. (P.S.); the Fred Hutchinson Cancer Research Center, Seattle (W.B.); State University of New York Upstate Medical University, Syracuse (T.G.); the University of Minnesota, Minneapolis (D.W., B.R.B.); Memorial Sloan-Kettering Cancer Center, New York (T.K.); the University of North Carolina, Chapel Hill (T.S.); Georgetown University Cancer Center, Washington, D.C. (S.Y.); the Northwest Marrow Transplant Center, Portland, Oreg. (K.H.); Sinai Hospital of Baltimore, Baltimore (S.N.); the Medical College of Virginia, Richmond (J.M.); the Texas Transplant Institute, San Antonio (C.F.L.); the School of Dentistry (E.C.S.) and the Division of Hematology/Oncology (C.E.), University of California at Los Angeles, Los Angeles; and Amgen, Thousand Oaks, Calif. (D.E., M.-G.C.).
Address reprint requests to Dr. Spielberger at the City of Hope National Medical Center, Department of Hematology and Hematopoietic Cell Transplantation and Kaiser Permanente BMT Program, 1500 E. Duarte Rd., Duarte, CA 91010, or at rspielberger{at}coh.org.
Palifermin and Chemotherapy-Induced Oral Mucositis
Awada A., Genot M.-T., Klastersky J., Köstler W. J., Hejna M., Zielinski C. C., Palmieri C., Vigushin D., Spielberger R., Stiff P., Bensinger W.
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N Engl J Med 2005;
352:1264-1265, Mar 24, 2005.
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