Palifermin for oral mucositis after intensive therapy for hematologic cancers.
BACKGROUND
Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy.


METHODS
This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 microg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days 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 and 98 percent in the placebo group (P<0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P<0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reported soreness 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 parenteral nutrition (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 and were transient.


CONCLUSIONS
Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers.
Spielberger
Ricardo
R
City of Hope National Medical Center, Department of Hematology and Hematopoietic Cell Transplantation and Kaiser Permanente BMT Program, Duarte, Calif 91010, USA. rspielberger@coh.org
Stiff
Patrick
P
Bensinger
William
W
Gentile
Teresa
T
Weisdorf
Daniel
D
Kewalramani
Tarun
T
Shea
Thomas
T
Yanovich
Saul
S
Hansen
Keith
K
Noga
Stephen
S
McCarty
John
J
LeMaistre
C Frederick
CF
Sung
Eric C
EC
Blazar
Bruce R
BR
Elhardt
Dieter
D
Chen
Mon-Gy
MG
Emmanouilides
Christos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003131:Combined Modality Therapy / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa; D009503:Neutropenia / Q000517:prevention & control; D010289:Parenteral Nutrition, Total / Q000706:statistics & numerical data; D011878:Radiotherapy / Q000009:adverse effects*; D013280:Stomatitis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D019172:Transplantation Conditioning / Q000009:adverse effects
D000970:Antineoplastic Agents; C496453:FGF7 protein, human; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors