GM-CSF with biochemotherapy (cisplatin, DTIC, tamoxifen, IL-2 and interferon-alpha): A phase I trial in melanoma

Citation
Mm. Vaughan et al., GM-CSF with biochemotherapy (cisplatin, DTIC, tamoxifen, IL-2 and interferon-alpha): A phase I trial in melanoma, ANN ONCOL, 11(9), 2000, pp. 1183-1189
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
ANNALS OF ONCOLOGY
ISSN journal
0923-7534 → ACNP
Volume
11
Issue
9
Year of publication
2000
Pages
1183 - 1189
Database
ISI
SICI code
0923-7534(200009)11:9<1183:GWB(DT>2.0.ZU;2-7
Abstract
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.