title: Phase I trial of r viscumin (INN: aviscumine) given subcutaneously in patients with advanced cancer: a study of the European Organisation for Research and Treatment of Cancer (EORTC protocol number 13001).
abstract: Safety of aviscumine by subcutaneous route was assessed in patients with advanced cancer refractory to chemotherapy. Patients with progressive disease received escalating doses twice weekly. Treatment of the accrued 26 patients (10 colorectal cancer (CRC), 6 soft tissue sarcoma (STS), 5 melanoma (MM), 5 others) was well tolerated without substance-related grade 3 or 4 toxicities. Grade 1/2 toxicities were predominantly injection site reactions. Aviscumine lacked dose-limiting toxicity (DLT) up to a maximal dose of 10 ng/kg. An increase of interleukin-1 beta and interferon-gamma from baseline was seen in the patient's plasma between the 1st and 11th injection. Highest release of both cytokines was in the dose range of 4-5.9 ng/kg. Interferon-gamma was not detected after doses higher than 6 ng/kg. Eight patients (5 CRC, 1 MM, 1 STS, 1 RCC) had disease stabilisation for 79-250 days (median122 days) associated with an increase of interleukin (IL)-1 beta and interferon (IFN)-gamma. Aviscumine was well tolerated and appeared to possess clinical activity at a biologically active dose between 4 and 6 ng/kg.
authors.affiliation: Klinikum der JW Goethe Universität, Medizinische Klinik III, Frankfurt, Germany. L.Bergmann@em.uni-frankfurt.de
authors.forename: Lothar
authors.initials: L
authors.lastname: Bergmann
authors.forename: Steiner
authors.initials: S
authors.lastname: Aamdal
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Denis
authors.initials: D
authors.lastname: Lacombe
authors.forename: Manfred
authors.initials: M
authors.lastname: Herold
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Karin
authors.initials: K
authors.lastname: Wilhelm-Ogunbiyi
authors.forename: Hans
authors.initials: H
authors.lastname: Lentzen
authors.forename: Heinz
authors.initials: H
authors.lastname: Zwierzina
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D028321:Plant Preparations / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D054790:Ribosome Inactivating Proteins, Type 2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014118:Toxins, Biological / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum