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)

Eur J Cancer. 2008 Aug;44(12):1657-62. doi: 10.1016/j.ejca.2008.05.005. Epub 2008 Jul 2.

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.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / pharmacokinetics
  • Administration, Cutaneous
  • Adult
  • Aged
  • Antibodies, Neoplasm / metabolism
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Plant Preparations / administration & dosage*
  • Plant Preparations / adverse effects
  • Plant Preparations / pharmacokinetics
  • Ribosome Inactivating Proteins, Type 2 / administration & dosage*
  • Ribosome Inactivating Proteins, Type 2 / adverse effects
  • Ribosome Inactivating Proteins, Type 2 / pharmacokinetics
  • Toxins, Biological / administration & dosage*
  • Toxins, Biological / adverse effects
  • Toxins, Biological / pharmacokinetics
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neoplasm
  • Antineoplastic Agents, Phytogenic
  • Plant Preparations
  • Ribosome Inactivating Proteins, Type 2
  • Toxins, Biological
  • ribosome inactivating protein, Viscum