Summary
Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame.
The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45–132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans.
Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2.
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References
Venditti JM, Wesley RA, Plowman J: Current NCI preclinical antitumor screeningin vivo results of tumor panel screening 1976–1982 and future directions. Adv Pharmacol Chemother 20:1–20, 1984
Driscoll NS: The preclinical new drug research program of the National Cancer Institute. Cancer Treat Report 68:63–76, 1984
Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977
Shoemaker RS, Wolpert-Defilippes MK, Kern DH, Lieber MM, Makuck RW, Melnick NR, Miller WT, Salmon SE, Simon RM, Venditti JM, Von Hoff DD: Application of a human tumor colony forming assay to drug screening. Cancer Res 45:2145–2153, 1985
Shoemaker RH: New approaches to antitumor screening: The human tumor colony forming assay. Cancer Treat Rep 70:9–12, 1986
Clinical Brochure for Chloroquinoxaline Sulfonamide, prepared by the Division of Cancer Treatment, National Cancer Institute, September 1988
Branda RF, McCormack JJ, Perlmutter C: Cellular pharmacology of chloroquinoxaline sulfonamide (CQS) and a related compound in murine B16 melanoma cells. Biochem Pharmacol 37(23):4557–4564, 1988
Siglan JC, Karcher R, Liao JT: Effect of leucovorin treatment on chlorsulfaquinoxaline (NSC-339004) induced toxicity in beagle dogs. Prepared by Springborn Laboratories for Toxicology Branch, Developmental Therapeutics Program, National Cancer Institute, NIH
Tong WP, Harishorn J, Mathews LA, Webster LK, McCormack JJ, Zaharko DS: Pharmacokinetic studies of chloroquinoxaline sulfonamide (CQS). Proc Amer Assoc Cancer Res 28:436, 1987
Branda RF, Moore AL, McCormack JJ: Immunosuppressive properties of chloroquinoxaline sulfonamide. Biochemical Pharmacology 38(20): 35226, 1989
Liao JT, Merriman TN, Collins WT, Hiles RA, Smith AC, Kastello MD, Zaharko DS, Grieshaber CK: Preclinical toxicologic and pharmacokinetic studies of chlorsulfaquinoxaline (NSC-339004). Proc Amer Assoc Cancer Res 28:441, 1987
McCormack JJ: Vermont Regional Cancer Center Task 16: Contract N01-CM-37606, DTP/DCT/NCI, December 1986
Rogers-Back A: Mouse lymphoma mutagenesis assay with chlorsulfaquinoxaline. Microbiological Associates, Inc. Contract N01-CP-41004, DTP/DCT/NCI, February 1986
Appel PL, Alley MC, Lieber MM, Shoemaker R, Powis G: Metabolic stability of chemotherapeutic agents in hepatocyte: tumor cell cocultures. Cancer Chemother Pharmacol 17:47–52, 1986
Rigas JR, Warrell RP Jr., Tong W, Farag FM, Baltzer L, Salvia B, Young CW: Phase I clinical/pharmacologic study of chloroquinoxaline sulfonamide. Proc Amer Assoc Cancer Res 31:177, 1990
Forrest A, Conley BA, Kloc C, Melink T, Sinibaldi V, Egorin MJ: A novel approach for modelling recycling phenome- na. Late peaks after IV chloroquinoxaline sulfonamide. Proc Amer Assoc Cancer Res 31:182, 1990
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Fisherman, J.S., Osborn, B.L., Chun, H.G. et al. Chloroquinoxaline sulfonamide: A sulfanilamide antitumor agent entering clinical trials. Invest New Drugs 11, 1–9 (1993). https://doi.org/10.1007/BF00873904
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DOI: https://doi.org/10.1007/BF00873904