Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF:: results of a prospective randomised trial

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. (C) 2001 Elsevier Science Ltd. All rights reserved.