Background: Ineffective tumour antigen processing is recognised as an impor
tant cause of failure of immunotherapy in melanoma. GM-CSF may augment the
cytotoxic lymphocyte response by activating antigen-presenting cells. This
study evaluates a schedule combining GM-CSF with biochemotherapy.
Patients and methods: Nineteen patients with advanced malignant melanoma re
ceived cisplatin (25 mg/m(2) days 1-3), dacarbazine (220 mg/m(2) days 1-3),
interleukin-2 (9 MIU/m(2)/24h) and interferon-alpha 2b (5 MIU/m(2)) both d
ays 6-10 and days 17-21, and tamoxifen 40 mg/day continuously. Subcutaneous
GM-CSF was given in escalating doses to three cohorts: 1) 450 mu g/m(2) da
ys 4-5 and 15-16; 2) as 1) plus 225 mu g/m(2) days 6-10 and 17-21; 3) 450 m
u g/m(2) days 4-10 and 15-21. Each cycle was 28 days.
Results: Constitutional side effects were the major non-haematological toxi
city and lymphopaenia the main haematological toxicity. Six patients respon
ded (32%, 95% confidence interval: 13%-57%), two patients had complete remi
ssion. There was an apparent trend for increasing responses with increasing
GM-CSF dose; zero of six responses in cohort 1, two of seven in cohort 2 a
nd three of six in cohort 3 (P = 0.016). Median overall survival was 6.2 mo
nths. Increasing GM-CSF doses significantly increased serum concentrations
of neopterin and TNF-alpha.
Conclusions: The combination of GM-CSF with biochemotherapy is feasible and
there appears to be a dose-response relationship with GM-CSF in terms of h
ost immunological response, and possibly clinical efficacy.