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Intratumoral administration of a 1,2‐dimyristyloxypropyl‐3‐ dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin‐2 gene in the treatment of metastatic renal cell carcinoma
Author(s) -
Galanis Evanthia,
Burch Patrick A.,
Richardson Ronald L.,
Lewis Bradley,
Pitot Henry C.,
Frytak Stephen,
Spier Catherine,
Akporiaye Emmanuel T.,
Peethambaram Prema P.,
Kaur Judith S.,
Okuno Scott H.,
Unni Krishnan K.,
Rubin Joseph
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20653
Subject(s) - medicine , chills , myalgia , renal cell carcinoma , nausea , gastroenterology , toxicity , surgery
BACKGROUND Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin‐2 (IL‐2) gene is complexed with the cationic lipid 1,2‐dimyristyloxypropyl‐3‐dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS Thirty‐one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment‐related toxicity. RESULTS Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low‐grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4–48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2–72 months), with a 1‐year survival rate of 48% and a 3‐year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL‐2 plasmid DNA in six of eight patients posttreatment, increased IL‐2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8‐positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma. Cancer 2004. © 2004 American Cancer Society.