title: Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial.
abstract: We have conducted a prospective controlled randomised clinical study testing for the efficacy of topical GM-CSF (molgramostim), as compared to the combined topical use of an antiseptic agent (povidone-iodine) and amphotericin B (AA) in patients with chemotherapy-induced mucositis World Health Organization (WHO) grades I-III. 31 patients (17 females, 14 males) developing oral mucositis following the administration of 5-fluorouracil (5-FU)-based chemotherapy were entered into the present trial. 15 patients were randomised to receive GM-CSF mouthwashes, whereas 16 patients were randomised into the control arm to receive AA. Reported history (P=0.6109) and grading of oral mucositis (2.1+/-0.7, respectively; P=0.9867) were balanced and equally distributed between the two groups. The mean size of lesions of oral mucositis was 1.5+/-0.6 cm (range: 0.7-2.5 cm) in the GM-CSF group and 1.2+/-0.5 cm (range: 0.5-2.5 cm) in the AA group (P=0.08), respectively. The mean number of oral mucositis lesions was 1.9+/-1.1 (range: 1-4) in the GM-CSF group and 2.1+/-1.2 (range: 1-4) in the AA group (P=0.63), respectively. None of the patients had previously received colony stimulating factors either topically or systemically. Treatment for oral mucositis was initiated on day 2.7+/-1.2 (range: day 1-8) after onset of symptoms in the GM-CSF group and on day 1.8+/-1.4 (range: day 1-3; P=0.11) in the AA group. The topical application of GM-CSF resulted in a significantly shorter duration and quicker resolution of oral mucositis, as compared to AA including both, pretreatment plus treatment periods (5.3+/-2.5 versus 8.1+/-1.5 days; P=0.0008) as well as the necessary duration of treatment needed until complete remission of lesions (2.8+/-0.7 versus 6.3+/-1.1 days; P<0.0001). A systemic effect of topical GM-CSF upon the number of peripheral blood leukocytes or granulocytes was excluded. We conclude that the topical application of GM-CSF by mouthwash significantly abbreviated the duration and relieved patients from symptoms of chemotherapy-induced mucositis and was superior to the topical application of AA.
authors.affiliation: Department of Medicine I, Division of Oncology, University Hospital, 18-20 Waehringer Guertel, A-1090, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hejna
authors.forename: W J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: M
authors.initials: M
authors.lastname: Raderer
authors.forename: G G
authors.initials: GG
authors.lastname: Steger
authors.forename: T
authors.initials: T
authors.lastname: Brodowicz
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
authors.forename: C
authors.initials: C
authors.lastname: Wiltschke
authors.forename: C C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa; D009067:Mouthwashes; D011206:Povidone-Iodine / Q000627:therapeutic use; D011446:Prospective Studies; D020011:Protective Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013280:Stomatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D009067:Mouthwashes; D020011:Protective Agents; D011994:Recombinant Proteins; D000666:Amphotericin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011206:Povidone-Iodine; C082430:molgramostim; D005472:Fluorouracil