title: Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.
abstract: Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 x 10(10) to 2 x 10(13) particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, gamma-IFN, TNF-alpha and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses > or = 2 x 10(12) particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 x 10(13) particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.
authors: US Oncology, Dallas, TX 75246, USA.
authors: J
authors: J
authors: Nemunaitis
authors: C
authors: C
authors: Cunningham
authors: A
authors: A
authors: Buchanan
authors: A
authors: A
authors: Blackburn
authors: G
authors: G
authors: Edelman
authors: P
authors: P
authors: Maples
authors: G
authors: G
authors: Netto
authors: A
authors: A
authors: Tong
authors: B
authors: B
authors: Randlev
authors: S
authors: S
authors: Olson
authors: D
authors: D
authors: Kirn
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000628:therapy; D000256:Adenoviridae / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy / Q000628:therapy*; D002291:Carcinoma, Papillary / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D003110:Colonic Neoplasms / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000628:therapy; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage; D013964:Thyroid Neoplasms / Q000628:therapy
chemical_list: D016190:Carboplatin; D017239:Paclitaxel