ISSN:
1569-8041
Keywords:
biochemotherapy
;
cytokines
;
GM-CSF
;
melanoma
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background:Ineffective tumour antigen processing is recognisedas an important cause of failure of immunotherapy in melanoma. GM-CSF mayaugment the cytotoxic lymphocyte response by activating antigen-presentingcells. This study evaluates a schedule combining GM-CSF with biochemotherapy. Patients and methods:Nineteen patients with advanced malignantmelanoma received cisplatin (25 mg/m2 days 1–3), dacarbazine(220 mg/m2 days 1–3), interleukin-2 (9 MIU/m2/24h)and interferon-α2b (5 MIU/m2) both days 6–10 and days17–21, and tamoxifen 40 mg/day continuously. Subcutaneous GM-CSF wasgiven in escalating doses to three cohorts: 1) 450 µg/m2 days4–5 and 15–16; 2) as 1) plus 225 µg/m2 days6–10 and 17–21; 3) 450 µg/m2 days 4–10 and15–21. Each cycle was 28 days. Results:Constitutional side effects were the majornon-haematological toxicity and lymphopaenia the main haematological toxicity.Six patients responded (32%, 95% confidence interval:13%–57%), two patients had complete remission. There wasan apparent trend for increasing responses with increasing GM-CSF dose; zeroof six responses in cohort 1, two of seven in cohort 2 and three of six incohort 3 (P = 0.016). Median overall survival was 6.2 months.Increasing GM-CSF doses significantly increased serum concentrations ofneopterin and TNF-α. Conclusions:The combination of GM-CSF with biochemotherapy isfeasible and there appears to be a dose-response relationship with GM-CSF interms of host immunological response, and possibly clinical efficacy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008348005349
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