title: First clinical experience using a 'pathotropic' injectable retroviral vector (Rexin-G) as intervention for stage IV pancreatic cancer.
abstract: Metastatic or non-resectable (stage IV) pancreatic cancer has a rapidly fatal outcome (median survival: 3-6 months), thus making gene therapy a viable therapeutic option. The objectives of the clinical studies are to evaluate the safety/toxicity and potential anti-tumor response/efficacy of intravenous (i.v.) infusions of a 'pathotropic' retroviral vector bearing a cytocidal gene construct (Rexin-G) as a gene transfer intervention for stage IV pancreatic cancer. An intra-patient dose escalation regimen was used wherein increasing doses of Rexin-G were given i.v. daily for 8-10 days. Completion of this regimen was followed by a one-week evaluation period for toxicity, after which, the maximum tolerated dose of Rexin-G was administered for another 8-10 days. In a second protocol, i.v. Rexin-G was administered frontline for 6 days followed by 8 doses of weekly gemcitabine. The NIH Common Toxicity Criteria Vs.2 was used to assess toxicity, and the NCI-RECIST criteria and tumor volume measurements were used to evaluate potential anti-tumor responses. We report the results of the first 3 patients that participated in the studies. Rexin-G arrested tumor growth in 3 of 3 patients without experiencing dose-limiting toxicity. No bone marrow suppression, significant alterations in liver and kidney function, nausea and vomiting, mucositis or hair loss were observed. Two patients are alive with stable disease approximately 5 and 14 months from diagnosis, and 1 patient is alive with progressive disease 20 months from diagnosis. The encouraging results of this first clinical experience will guide the design and planning of phase I/II clinical trials to establish the safety and efficacy of Rexin-G as the first targeted injectable gene therapy vector for stage IV pancreatic cancer.
authors.affiliation: Epeius Biotechnologies Corporation, Glendale, CA 91203, USA. emgordon@epeiusbiotech.com
authors.forename: Erlinda M
authors.initials: EM
authors.lastname: Gordon
authors.forename: Gerardo H
authors.initials: GH
authors.lastname: Cornelio
authors.forename: Conrado C
authors.initials: CC
authors.lastname: Lorenzo
authors.forename: John P
authors.initials: JP
authors.lastname: Levy
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Reed
authors.forename: Liqiong
authors.initials: L
authors.lastname: Liu
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Hall
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000008:administration & dosage / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine