TY - JOUR
T1 - Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex
T2 - Phase I/II experience
AU - Galanis, Evanthia
AU - Hersh, E. M.
AU - Stopeck, A. T.
AU - Gonzalez, R.
AU - Burch, P.
AU - Spier, C.
AU - Akporiaye, E. T.
AU - Rinehart, J. J.
AU - Edmonson, J.
AU - Sobol, R. E.
AU - Forscher, C.
AU - Sondak, V. K.
AU - Lewis, B. D.
AU - Unger, E. C.
AU - O'Driscoll, M.
AU - Selk, L.
AU - Rubin, J.
PY - 1999/10
Y1 - 1999/10
N2 - Purpose: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl- phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. Patients and Methods: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 μg, 30 μg, or 300 μg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 μg twice a week for 3 weeks, 750 μg weekly for 6 weeks, and 1,500 μg weekly for 6 weeks. Results: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8+ infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). Conclusion: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.
AB - Purpose: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl- phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. Patients and Methods: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 μg, 30 μg, or 300 μg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 μg twice a week for 3 weeks, 750 μg weekly for 6 weeks, and 1,500 μg weekly for 6 weeks. Results: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8+ infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). Conclusion: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.
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U2 - 10.1200/JCO.1999.17.10.3313
DO - 10.1200/JCO.1999.17.10.3313
M3 - Article
C2 - 10506635
AN - SCOPUS:0032886544
SN - 0732-183X
VL - 17
SP - 3313
EP - 3323
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -