ONCOLOGY Vol 19 No 4_Suppl_2

Patients having locoregional or metastatic melanoma have a poorprognosis, with 50% to 100% of patients dying from the disease within5 years. Current chemotherapy regimens offer limited benefits to thesepatients, and more effective and less toxic treatments are needed. Wetherefore piloted a study of docetaxel (Taxotere), vinorelbine(Navelbine), granulocyte-macrophage colony-stimulating factor(GM-CSF, sargramostim [Leukine]), or the DVS regimen, in patientswith stage IV melanoma. Eight patients were treated after previousbiochemotherapy and two patients were given the regimen as an initialtreatment. The DVS regimen consisted of docetaxel at 40 mg/m2 IVover 1 hour, vinorelbine at 30 mg/m2 IV over 6 to 10 minutes every 14days, and GM-CSF at 250 mg/m2 SC on days 2 to 12. No grade 3 or 4toxicities were encountered. Of the 10 patients evaluable for response, 5were partial responders (50% response rate). Time to progression for the10 cases ranged from 2 to 26+ months (median: 8 months). The DVSregimen was active against advanced melanoma in both previously treatedand untreated patients. A larger study to confirm the activity of the DVSregimen for stage IV melanoma is currently under way.

Cytokines have been used in the treatment of patients with cutaneousmelanoma. Granulocyte-macrophage colony-stimulating factor(GM-CSF, sargramostim [Leukine]) leads to dendritic cell/macrophagepriming and activation, and also increases interleukin-2 (IL-2)receptor expression on T lymphocytes. IL-2 creates lymphokineactivatedkiller cells and tumor-infiltrating lymphocyte cells. In thisopen-label, single-arm study of 16 high-risk patients, we combined thesetwo agents to take advantage of their different but complementary functions.All patients underwent potentially curative surgery. Postoperatively,each patient received GM-CSF at 125 μg/m2/d subcutaneously(SC) for 14 days; this was followed by IL-2 at 9 million IU/m2/d SC for4 days, and then 10 to 12 days of no treatment. In addition, patientswho had large tumors that could yield over 100 million live tumor cellsreceived autologous melanoma vaccines. The duration of follow-upranged from 21 to 42 months (median: 27 months). During follow-up,five patients developed metastases. This program was carried out on anoutpatient basis, and no hospitalization was required. It was well toleratedwith minimal side effects. The combination treatment regimen ofGM-CSF and IL-2 with or without autologous vaccine used adjuvantlyappears to benefit high-risk melanoma patients; further clinical testingof this regimen is warranted.

Colony-stimulating factors are glycoproteins that act on hematopoietic cellsby binding to specific cell surface receptors and stimulating proliferation,differentiation commitment, and a degree of end-cell functional activation.Granulocyte colony-stimulating factor (G-CSF), produced by monocytes,fibroblasts, and endothelial cells, regulates the production of neutrophils within thebone marrow and affects neutrophil progenitor proliferation.[1,2]

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.