Phase I trials of poly(I,C) complexes in advanced cancer.
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.
S E
SE
Krown
D
D
Kerr
W E
WE
Stewart
A K
AK
Field
H F
HF
Oettgen
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity / Q000031:analogs & derivatives; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007372:Interferons / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000188:drug therapy; D007694:Killer Cells, Natural / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011107:Polylysine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity / Q000031:analogs & derivatives
D011107:Polylysine; C040125:poly ICL; C019531:poly ICLC; D008747:Methylcellulose; D007372:Interferons; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C