Interferon-gamma or granulocyte-macrophage colony-stimulating factor administered as adjuvants with a vaccine of irradiated autologous tumor cells from short-term cell line cultures: a randomized phase 2 trial of the cancer biotherapy research group.

The objective was to study the effects of patient-specific vaccine immunotherapy administered with either interferon-gamma (IFNgamma) or granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with metastatic cancer. Short-term cell lines were established from cancer tissue resected from patients with metastatic cancer for use as autologous tumor cell vaccines. Successful cultures were expanded to 1 to 2 x 108 cells, irradiated, and cryopreserved in aliquots of 106 cells for intradermal testing of delayed tumor hypersensitivity and 107 cells for subcutaneous vaccinations. The study design was that of a randomized phase 2 trial. Patients were stratified by tumor type and by whether they had measurable disease at the time vaccination was to commence, and then randomized to receive either 100 MIU IFNgamma subcutaneously or 500 microg GM-CSF subcutaneously at the time of each tumor cell vaccination. Following a baseline test of delayed-type hypersensitivity (DTH) to an intradermal injection of 106 irradiated autologous tumor cells, patients received 3 weekly subcutaneous injections of 107 cells, had a repeat DTH test at week 4, then received monthly vaccinations for 5 months. A positive DTH test was defined as at least 10 mm of induration; survival was determined from the first DTH test. There were 98 patients enrolled with a median follow-up of over 4 years. The most prevalent diagnoses were melanoma (51), renal cell carcinoma (18), and soft-tissue sarcoma (14). There were 49 patients (26 men, 23 women, average age 50.4 years) randomized to IFNgamma and 49 (28 men, 21 women, average age 54.1 years) to GM-CSF. The average numbers of vaccine and adjuvant injections were 6.3 and 5.9, respectively. For the patients who received IFNgamma, the objective response rate was 0 of 21; for patients who received GM-CSF the response rate was 1 of 26. Only eight patients (four from each arm) had a positive baseline DTH reaction to autologous tumor. The tumor DTH test converted from negative to positive in 13 of 45 of the IFNgamma group and 11 of 43 of the GM-CSF group. With 29 patients deceased in the IFNgamma arm and 31 in the GM-CSF arm, the 2-year and 5-year survival rates were 45% and 29% for the IFNgamma arm and 41% and 23% for the GM-CSF arm (NSD). Both adjuvants were well tolerated and results were similar in both arms of the study. Both adjuvants were associated with a 25% to 30% rate of DTH conversion and a 25% 5-year survival rate. Immune recognition of autologous tumor can be induced with this approach.

RCT Entities:   Population Interventions Outcomes