EVALUATION OF GM-CSF MOUTHWASH FOR PREVENTION OF CHEMOTHERAPY-INDUCEDMUCOSITIS - A RANDOMIZED, DOUBLE-BLIND, DOSE-RANGING STUDY

Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis. Th e mechanism of this effect could be related to acceleration of haemato poiesis and/or increase in functional activation of WBC. We conducted a double-blind, placebo-controlled, dose ranging study of GM-CSF (molg ramostim) mouthwash in patients with breast cancer during the first tr eatment cycle of a combination chemotherapy regimen which has historic ally produced dose-limiting (grade greater than or equal to 3) mucosit is in approximately 39% of patients. Subjects were randomized to recei ve either placebo mouthwash (0.1 percent albumin) or one of four conce ntrations of GM-CSF mouthwash (0.01, 0.1, 1.0 or 10 mcg/ml). The prima ry endpoint was to evaluate the relationship between dose of GM-CSF mo uthwash received and probability of grade greater than or equal to 3 m ucositis using a logistic model. Solutions were administered four time s daily starting within 24 hours of chemotherapy initiation and contin uing until the end of the cycle (day 21). Mucositis was assessed on da ys 1-6, 10, 15 and 21. Day 6 plasma samples were assayed for GM-CSF. F orty-five patients were evaluable for response (nine per dosing group) . A 42% risk (15/36) of mucositis grade greater than or equal to 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 pat ients on the placebo arm. No evidence of dose response was found by lo gistic 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). (C) 1995 Academic Press L imited.