Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

<p>Abstract</p> <p>Background</p> <p>Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.</p> <p>Methods</p> <p>The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity.</p> <p>Results</p> <p>Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by <it>in vitro </it>immune monitoring assays.</p> <p>Conclusions</p> <p>The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.</p> <p>Clinical trial registration</p> <p>NCT00107159.</p

Phase II trial of biochemotherapy with interferon α, dacarbazine, cisplatin and tamoxifen in metastatic melanoma: a Southwest Oncology Group trial

The therapeutic benefit of adding interferon α (IFNα) to established single-agent and combination chemotherapy regimens for the treatment of metastatic melanoma has not been proven. We designed the present study to estimate the response rate of IFNα, dacarbazine, cisplatin and tamoxifen in patients who had not been treated with systemic therapy for advanced disease. Using a schedule similar to that which had previously been shown to favor IFNα plus dacarbazine over dacarbazine alone, we treated patients with an “induction” regimen of IFNα, 15 mU m −2 day −1 intravenously 5 days/week for 3 weeks. Following induction, schedules of IFNα, 5 mU m −2  day −1 subcutaneously three times a week, and tamoxifen, 10 mg orally twice a day, were begun. Dacarbazine, 250 mg m −2  day −1 and cisplatin 33 mg m −2  day −1 for 3 consecutive days were repeated every 4 weeks, and subcutaneous IFNα and oral tamoxifen were continued until the discontinuation of chemotherapy. We treated 25 patients (18 men and 7 women, median age 52 years) and observed only 1 objective response (response rate 4%, 95% confidence interval 0.1%–20%). The toxicities of the regimen consisted of moderate myelosuppression and constitutional side-effects. On the basis of the low antitumor activity of this regimen, we do not recommend it for further study or for use as standard therapy of metastatic melanoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42256/1/432-125-5-292_91250292.pd

Epilesional Scarification: Preliminary Report of a New Approach to Local Immunotherapy With BCG

Because of the serious toxicity of intralesionally injected BCG, including high fever, local ulceration, chronic drainage, and disseminated BCG disease, 13 patients received local BCG immunotherapy by the new approach of epilesional scarification. Three patients had complete responses, four had partial responses, and six had no response. Toxic reactions were minimal compared to those reported for intralesionally given BCG.(JAMA 234:1233-1235, 1975

BCG Vaccine and Its Derivatives: Potential, Practical Considerations, and Precautions in Human Cancer Immunotherapy

BCG vaccine is undergoing extensive clinical trials for cancer immunotherapy. These studies are based on its immunopotentiating and macrophage-activating properties. Efficacy of BCG vaccine probably depends on strain, proportion of viable organisms, absence of free soluble antigens, dose, route, and schedule of administration. BCG vaccine is most efficacious when administered in conjunction with or following intensive cytoreductive maneuvers such as surgery, radiotherapy, or chemotherapy. BCG vaccine has shown beneficial activity in acute myelogenous leukemia, malignant melanoma, colon cancer, lymphoma, head and neck cancer, and other tumors. Since BCG vaccine has toxic side effects, and since less than optimal preparations can be detrimental in terms of tumor control, progress in the development of BCG vaccine immunotherapy must be based on sound clinical trials, careful clinical and immunological evaluation of treated subjects, and continuing research on basic and applied aspects of its immunological and other biological activities.(JAMA 235:646-650, 1976