title: Evaluation of GM-CSF mouthwash for prevention of chemotherapy-induced mucositis: a randomized, double-blind, dose-ranging study.
abstract: Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis. The mechanism of this effect could be related to acceleration of haematopoiesis and/or increase in functional activation of WBC. We conducted a double-blind, placebo-controlled, dose ranging study of GM-CSF (mol-gramostim) mouthwash in patients with breast cancer during the first treatment cycle of a combination chemotherapy regimen which has historically produced dose-limiting (grade > or = 3) mucositis in approximately 39% of patients. Subjects were randomized to receive either placebo mouthwash (0.1 percent albumin) or one of four concentrations of GM-CSF mouthwash (0.01, 0.1, 1.0 or 10 mcg/ml). The primary endpoint was to evaluate the relationship between dose of GM-CSF mouthwash received and probability of grade > or = 3 mucositis using a logistic model. Solutions were administered four times daily starting within 24 hours of chemotherapy initiation and continuing until the end of the cycle (day 21). Mucositis was assessed on days 1-6, 10, 15 and 21. Day 6 plasma samples were assayed for GM-CSF. Forty-five patients were evaluable for response (nine per dosing group). A 42% risk (15/36) of mucositis grade > or = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 patients on the placebo arm. No evidence of dose response was found by logistic regression. Five patients had a detectable plasma concentration of GM-CSF (56-209 pg/ml). A positive correlation between GM-CSF dose and leukocyte recovery was noted (P = 0.04).
authors.affiliation: Duke University Bone Marrow Transplant Program, Durham, N.C., USA.
authors.forename: L
authors.initials: L
authors.lastname: Cartee
authors.forename: W P
authors.initials: WP
authors.lastname: Petros
authors.forename: G L
authors.initials: GL
authors.lastname: Rosner
authors.forename: C
authors.initials: C
authors.lastname: Gilbert
authors.forename: S
authors.initials: S
authors.lastname: Moore
authors.forename: M L
authors.initials: ML
authors.lastname: Affronti
authors.forename: J A
authors.initials: JA
authors.lastname: Hoke
authors.forename: A M
authors.initials: AM
authors.lastname: Hussein
authors.forename: M
authors.initials: M
authors.lastname: Ross
authors.forename: P
authors.initials: P
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018567:Breast Neoplasms, Male / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004317:Doxorubicin / Q000009:adverse effects; D005069:Evaluation Studies as Topic; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D009061:Mouth Mucosa / Q000187:drug effects*; D009067:Mouthwashes / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D009067:Mouthwashes; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil; D008727:Methotrexate