In the present open non-randomized phase II study we looked for effectiveness, safety, tolerability and costs of locally applied
GM-CSF in preventing or treating
mucositis in patients receiving
chemotherapy or
chemoradiotherapy for
head and neck cancer. In addition to clinical
mucositis scoring system, the effects of treatment with
GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory
cytokines,
IL-2 and
leptin. The trial was designed to assess the effectiveness of local
GM-CSF treatment in two different settings: i) prophylaxis of
mucositis; ii) treatment of
mucositis. Prophylaxis was chosen for
chemoradiotherapy treatments of high mucosatoxic potential, while curative treatment was reserved for
chemotherapy or
chemoradiotherapy treatments of lesser potential of inducing
mucositis. From January 1998 to December 2001, 68 patients entered the study. The great majority of patients of both groups had
head and neck cancer, were stage IV, PS ECOG 0-1, were habitual smokers and were treated with
chemotherapy and concomitant (or sequential)
chemoradiotherapy. Forty-six patients were included in the 'prophylactic' setting and 22 patients in the 'curative' setting. The main findings of our study are: only 50% of patients included in the 'prophylactic' setting developed
mucositis; the duration of
oral mucositis from appearance until complete remission was significantly shorter in the 'prophylactic' than in the 'curative' setting; the mean grade of
oral mucositis at baseline, on day 3 of
therapy and on day 6 of
therapy was significantly lower in the 'prophylactic' than in the 'curative' setting; 24 (55.82%) patients in the 'prophylactic' setting had grade 3/4
oral mucositis at baseline compared to 25 (80.60%) patients in the 'curative' setting (p=0.048). Thirteen (30.23%) patients in the 'prophylactic' setting had grade 3/4
oral mucositis on day 3 of
therapy compared to 19 (61.29%) patients in the 'curative' setting (p=0.015); 'prophylactic' setting was able to shorten grade 3/4
oral mucositis to grade 0/1 more effectively than the 'curative' one on day 6 of
therapy (p=0.05). The present clinical trial is to date by far the largest study assessing the effectiveness of topical
GM-CSF and it is the first study comparing the efficacy of topical
GM-CSF in the 'prophylactic' setting, i.e., with the aim to prevent the
chemoradiotherapy-induced
oral mucositis, with that in the 'curative' treatment, i.e., the
therapy for established
oral mucositis. The topical application of
GM-CSF was demonstrated to be effective for
oral mucositis induced by
chemotherapy and
chemoradiotherapy regimens. Moreover, the 'prophylactic' setting was demonstrated to be more effective than the 'curative' one.