methylcellulose and Leukopenia

We have performed Phase I trials of two synthetic double-stranded polyribonucleotide complexes--poly(I,C)-LC, a complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxymethylcellulose, and poly(I,C)-L, which lacks carboxymethylcellulose--in patients with advanced cancer. With poly(I,C)-LC, several treatment schedules were investigated in an attempt to decrease toxicity and maximize interferon (IFN) induction. The best tolerated was an alternate-day schedule, with gradual dose escalation. Daily short infusions and continuous (24-h) infusions were tolerated less well. Maximum tolerated doses varied over a several hundredfold dose range. Toxicity consisted of fever, rigors, hypotension, and blood count depression. Two patients treated with poly(I,C)-L developed systemic allergic reactions, and antibodies to poly(I,C)-L and its components were detected in the serum of some patients treated with both compounds. IFN-alpha was induced in most patients at serum levels similar to those achieved after intramuscular administration of human IFN-alpha. Of 32 patients, one with renal cell carcinoma showed partial tumor regression. Poly(I,C) complexes are effective IFN inducers in humans, but their toxicity limits their use in cancer patients.

Topics: Adult; Aged; Antibody Formation; Carboxymethylcellulose Sodium; Carcinoma, Renal Cell; Drug Evaluation; Drug Tolerance; Female; Humans; Hypotension; Interferons; Kidney Neoplasms; Killer Cells, Natural; Leukopenia; Male; Methylcellulose; Middle Aged; Neoplasms; Poly I-C; Polylysine

Topics: Animals; B-Lymphocytes; Hypersplenism; Leukocyte Count; Leukopenia; Methylcellulose; Rats; Rats, Inbred Strains; Spleen; Splenomegaly; T-Lymphocytes; Thrombocytopenia

Poly(ICLC) preparation, containing poly-L-lysine and poly(I) . poly(C) at a weight ratio of 1:2, was given intravenously at a dose of 0.05 to 0.2 mg/kg to 7 patients with malignant brain tumor. Poly(ICLC) induced significant serum interferon (more than 100 reference units/ml) in all patients. The highest interferon titer induced was 875 reference units/ml. Severe side effect was not observed except fever. Hypotension, leukopenia and elevation of liver enzyme levels were observed as side effects in a few cases.

Topics: Adult; Brain Neoplasms; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Humans; Hypotension; Interferon Inducers; Interferons; Leukopenia; Liver; Male; Methylcellulose; Middle Aged; Molecular Weight; Peptides; Poly I-C; Polylysine

Topics: Aminopyrine; Bone Marrow Diseases; Hematopoietic System; Humans; Leukopenia; Methylcellulose; Primaquine; Spleen

Topics: Kidney Diseases; Leukopenia; Liver Diseases; Lung Diseases; Lymph Nodes; Lymphocytosis; Metabolic Diseases; Methylcellulose; Pathology; Rats; Research; Spleen; Toxicology