Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.

Objectives-Early testing of aerosolized sargramostim therapy demonstrated anecdotal clinical responses in patients with metastatic melanoma associated with emergence of systemic anti-tumor immunity. In order to improve the clinical and immunological efficacy of therapy without compromising patient safety, we performed a further dose escalation trial in patients with metastatic melanoma.Methods-We conducted a dose-escalation clinical trial of HLA-A2 + patients with metastatic melanoma to the lung treated with aerosolized GM-CSF (500-2000ug/dose, with increments of 250ug/dose/cohort) twice/day on days 1-7 & 15-21 every 28 days until progression or severe toxicity to find a dose where majority of patients develop anti-tumor immunity. Five patients were treated per each dose level. Clinical, immune, and safety parameters were examined.Results-The study accrued 40 patients. Toxicity was acceptable. All doses levels were exhausted without identifying a dose of GM-CSF at which majority of patients (≥ 3 of 5) demonstrated significant up-regulation of anti-tumor immunity. Three of 16 patients that were tetramer positive for at least one melanoma antigen (e.g. MART-1) pre-treatment developed an immune response (IR) to different tumor antigens. Two of 9 patients who were tetramer negative to all melanoma antigens pre-treatment developed an IR against gp100. The greatest changes in anti-tumor immunity occurred at the highest dose levels.Conclusions-A dose of aerosolized GM-CSF capable of inducing anti-tumor immunity in the majority of patients was not reached. All tested doses were well tolerated. The greatest increase in anti-tumor T cell immune responses was achieved at the highest doses of GM-CSF.

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