A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC)

  • Tanios S. Bekaii-Saab
  • Amir Mortazavi
  • Lee G. Hicks
  • Mark Zalupski
  • Robert J. Pelley
  • Kenneth K. Chan
  • Eric H. Kraut
Phase II Studies


Purpose: Phase II multicenter study investigated the efficacy and toxicity of the novel halogenated derivative of sulfaquixonaline Chloroquinoxaline Sulfonamide (CQS) in metastatic colorectal cancer. Experimental design: Eligible patients with metastatic or recurrent colorectal cancer received CQS at a dose schedule of 2000 mg/m2 over an hour weekly for 4 weeks every 42 days. Treatment was continued until unexpected toxicity or disease progression. Results: A total of seventeen patients were enrolled on this study. 94% of all patients enrolled had prior treatment. Sixteen patients were evaluable for response with fifteen patients showing evidence of disease progression and one patient with prolonged stable disease. One patient had non-evaluable disease. Following this interim analysis, the drug was considered ineffective and the study was terminated early. The most frequent adverse event was anemia. No patients discontinued the treatment because of toxicity. Conclusion: CQS, when given at a dose of 2000 mg/m2 weekly for 4 weeks every 42 days to patients with metastatic colorectal cancer, does not result in significant tumor regression.


colon cancer Chloroquinoxaline Sulfonamide metastatic investigational drug 


  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ: Cancer statistics, 2005. CA Cancer J Clin 55(1):10–0, 2005CrossRefPubMedGoogle Scholar
  2. 2.
    Pazdur R., Coia LR, Wagman LD, Ayoub JP: Colorectal and Anal Cancers. In: Cancer Management: A Mulitidisciplinary Approach. Third Edition. Ed. By Pazdur R, Coia L, Hoskins WJ,Wagman LD. PRRR, Huntington NY, 1999Google Scholar
  3. 3.
    Tong WP, Hartshorn J, Mathews LA: Chloroquinoxaline sulfonamide, investigational drug brochure. National Cancer Institute, Division of Cancer treatment, 1987Google Scholar
  4. 4.
    Branda RF, McCormack JJ, Perlmutter CA: Cellular pharmacology of chloroquinoxaline sulfonamide and a related compound in murine B16 melanoma cells. Biochem Pharmacol. 37(23):4557–564, 1988CrossRefPubMedGoogle Scholar
  5. 5.
    Gao H, Yamasaki EF, Chan KK, Shen LL, Snapka RM: Chloroquinoxaline sulfonamide (NSC 339004) is a topoisomerase IIa/β poision. Cancer Res 60: 5937–940, 2000PubMedGoogle Scholar
  6. 6.
    Hickey R, Schiffer J, Wei Y, Malkas L: DNA synthesis is differentially affectd by the drugs mebarone and chloroquinoxaline. Proc Am Assoc Cancer Res 34:352, 1993Google Scholar
  7. 7.
    Branda RF, Moore AL, McCormack JJ: Immunosuppressive properties of chloroquinoxaline sulfonamide. Biochem Pharmacol 38: 3521–526, 1989CrossRefPubMedGoogle Scholar
  8. 8.
    Rigas JR, Tong WP, Kris MG, Orazem JP, Young CW, Warrell RP Jr: Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide. Cancer Res 52(23):6619–623, 1992PubMedGoogle Scholar
  9. 9.
    Conley BA, O’Hara S, Wu S, Melink TJ, Parnes H, Pardoe E, Egorin MJ, Van Echo DA: Phase I trial of chloroguinoxaline sulfonamide, with correlation of its pharmacokinetics and pharmacodynamics. Cancer Chemother Pharmacol 37(1–2):139–49, 1995CrossRefPubMedGoogle Scholar
  10. 10.
    Rigas JR, Francis PA, Miller VA, Tong WP, Roistacher N, Kris MG, Orazem JP, Young CW, Warrell RP Jr: Clinical and pharmacology study of chloroquinoxaline sulfonamide given on a weekly schedule. Cancer Chemother Pharmacol 35(6):483–88, 1995CrossRefPubMedGoogle Scholar
  11. 11.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92(3):205–16, 2000CrossRefPubMedGoogle Scholar
  12. 12.
    Rothenberg ML, Oza AM, Bigelow RH, Berlin JD, Marshall JL, Ramanathan RK, Hart LL, Gupta S, Garay CA, Burger BG, Le Bail N, Haller DG: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III Trial. JCO 2059–069, 2003Google Scholar
  13. 13.
    Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22(2):229–37, 2004CrossRefPubMedGoogle Scholar
  14. 14.
    Kim R, Ohi Y, Inoue H, Toge T: Expression and relationship between topoisomerase I and II alpha genes in tumor and normal tissues in esophageal, gastric and colon cancers. Anticancer Res. 19(6B):5393–398, 1999PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Tanios S. Bekaii-Saab
    • 1
    • 2
  • Amir Mortazavi
    • 1
  • Lee G. Hicks
    • 3
  • Mark Zalupski
    • 4
  • Robert J. Pelley
    • 5
  • Kenneth K. Chan
    • 6
  • Eric H. Kraut
    • 1
  1. 1.Division of Hematology and Oncology, Department of MedicineThe Ohio State University-James Cancer HospitalColumbus
  2. 2.Department of PharmacologyColumbus
  3. 3.Central Baptist HospitalLexington
  4. 4.Division of Hematology and OncologyUniversity of MichiganAnn Arbor
  5. 5.Division of Hematology and OncologyCleveland ClinicCleveland
  6. 6.Colleges of Pharmacy and Medicine and Public HealthThe Ohio State UniversityColumbus

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