methylcellulose and Kidney-Neoplasms

Polyinosinic-polycytidylic acid, a double-stranded ribonucleic acid that is a potent inducer of interferon production, was used in a stabilized form to treat 11 patients with metastatic renal cell carcinoma. Seven patients completed a full course of 8 infusions at maximum tolerated dosage. All patients experienced transient fever and marked fatigue. Anorexia was mild. Transient leukopenia occurred in 3 patients and reversible elevation in creatinine was observed in 1. All 4 patients with brain metastases became lethargic, and 3 died during or shortly after therapy. Only 2 patients demonstrated measurable total regression of isolated metastases (pleural/pulmonary in 1 and bone in 1) but in both metastases at other sites progressed. No partial regressions were seen. Metastases at all other sites (liver, brain and renal fossa) progressed during therapy. Patients who appeared to respond and who performed best during therapy generally demonstrated a higher performance status initially. Expression of natural cytotoxicity in in vitro testing did not correlate with a demonstrated response to treatment.

Topics: Bone Neoplasms; Brain Neoplasms; Carboxymethylcellulose Sodium; Carcinoma, Renal Cell; Humans; Interferon Inducers; Kidney Neoplasms; Lung Neoplasms; Methylcellulose; Poly I-C; Polylysine

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; Carboxymethylcellulose Sodium; Dextrans; Drug Combinations; Embolization, Therapeutic; Humans; Iodamide; Iodobenzoates; Iron; Kidney Neoplasms; Liver Neoplasms; Magnetics; Male; Methylcellulose; Middle Aged; Rabbits

Topics: Animals; Carcinoma, Ehrlich Tumor; Female; Injections, Intraperitoneal; Injections, Intravenous; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Methylcellulose; Mice; Neoplasm Metastasis; Polysaccharides; Resins, Plant; Sarcoma 180; Time Factors