Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

British Journal of Cancer

Volumn 79, Issue 9-10, 1999, Pages 1454-1461

  Awada, A ^a   Punt, C J A ^b   Piccart, M J ^a   Van Tellingen, O ^c   Van Manen, L ^b   Kerger, J ^a   Groot, Y ^d   Wanders, J ^d   Verweij, J ^e   Wagener, D J Th ^b  

^a JULES BORDET INSTITUTE   (Belgium)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c NETHERLANDS CANCER INSTITUTE   (Netherlands)

^d New Drug Development Office   (Netherlands)

^e ERASMUS MC CANCER INSTITUTE   (Netherlands)

Author keywords

Alkylating agent; Carzelesin; Pharmacodynamics; Pharmacokinetics; Phase I

Indexed keywords

CARZELESIN;

ADULT; ADVANCED CANCER; AGED; ANOREXIA; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG TOLERANCE; FEMALE; FEVER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MAJOR CLINICAL STUDY; MALE; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SOLID TUMOR; THROMBOCYTOPENIA; VOMITING;

EID: 0033014899     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjc.6690232     Document Type: Article

References (17)

1. D'Incalci M (1994) DNA-minor-groove alkylators, a new class of anticancer agents. Ann Oncol 5: 877-878
2. EORTC-NDDO report (1992) Toxicology studies of Carzelesin (U-80244)
3. Fleming GF, Ratain MJ, O'Brien SM, Schilsky RL, Hoffman PC, Richards JM, Vogelzang NJ., Kasunic DA, Earhart RH (1994) Phase I study of adozelesin administered by 24-hour continuous intravenous infusion. J Natl Cancer Inst 86: 368-372
4. Houghton PJ, Cheshire PJ, Hallman JDn, Houghton JA (1995) Therapeutic efficacy of the cyclopropylpyrroloindole, Carzelesin, against xenografts derived from adult and childhood solid tumors. Cancer Chemother Pharmacol 36: 45-52
5. Hurley LH, Reynolds VL, Swenson DH, Petzold GL, Scahill TA (1984) Reaction of the antitumor antibiotic CC-1065 with DNA: structure of a DNA adduct with DNA sequence specificity. Science 226: 843-844
6. Jonkman-de Vries JD, de Graaff-Teulen JA, Henrar REC, Kettenes-van-den-Bosch JJ, Bult A and Beijnen JH (1994) Pharmaceutical development of a parenteral formulation of the novel antitumour agent Carzelesin (U-80,244). Invest New Drugs 12: 303-314
7. Lee CS, Gibson NW (1991) DNA damage and differential cytotoxicity produced in human carcinoma cells by CC-1065 analogues, U-73,975 and U-77,779. Cancer Res 51: 6586-6591
8. Li LH, DeKoning TF, Kelly RC, Krueger WC, McGovren JP, Padbury GE, Petzold GL, Wallace TL, Ouding RJ, Prairie MD, Gebhard I (1992) Cytotoxicity and antitumour activity of Carzelesin, a prodrug cyclopropylpyrroloindole analogue. Cancer Res 52: 4904-4913
9. McGovren JP, Clarke GL, Pratt EA, DeKoning TF (1984) Preliminary toxicity studies with the DNA-binding antibiotic, CC-1065. J Antibiot (Tokyo) 37: 63-70
10. Reynolds VL, Molineux IJ, Kaplan DJ, Swenson DH, Hurley LH (1985) Reaction of the antitumor antibiotic CC-1065 with DNA location of the site of thermally induced strand breakage and analysis of DNA sequence specificity. Biochemistry 24: 6228-6237
11. Sessa C, Pagani O, Zurlo MG, de Jong J, Hofmann C, Lassus M, Marrari P, Strolin Benedetti M, Cavalli F (1994) Phase I study of the novel distamycin derivative tallimustine (FCE 24517). Ann Oncol 5: 901-907
12. Shamdas GJ, Alberts DS, Modiano M, Wiggins C, Power J, Kasunic DA, Elfring GL, Earhart RH (1994) Phase I study of adozelesin (U-73975) in patients with solid tumours. Anticancer Drugs 5: 10-14
13. Van Tellingen O, Pels EM, Henrar REC, Schaaf LJ, Padbury GE, Beijnen JH, Nooijen WJ (1994a) Fully automated high-performance liquid chromatographic method for the determination of Carzelesin (U-80,244) and metabolites (U-76,073 and U-76,074) in human plasma. J Chromatogr 652: 51-58
14. Van Tellingen O, Beijnen JH, Nooijen WJ, van Oene S, Henrar REC, Schaaf LJ, Padbury GE (1994b) Plasma pharmacokinetics of Carzelesin (U-80,244) and metabolites (U-76,073,U-76,74) in mice and rats. Ann Oncol 5(suppl 5): 171 (Abstract)
15. Van Tellingen O, Punt CJA, Awada A, Wagener DJT, Piccart MJ, Groot Y, Schaaf LJ, Henrar REC, Nooijen WJ, Beijnen JH (1998) A clinical pharmacokinetics study of Carzelesin given by short-term intravenous infusion in a phase I study. Cancer Chemother Pharmacol 41: 377-384
16. Warpchoski MA and Hurley LH (1988) Sequence selectivity of DNA covalent modification. Chem Res Toxicol 1: 315-333
17. Wolf I, Bench K, Beijnen JH, Bruntsch U, Cavalli F, de Jong J, Groot Y, Van Tellingen O, Wanders J and Sessa C (1996) Phase I clinical and pharmacokinetic study of Carzelesin (U-80,244) given on a daily x 5 schedule. Clin Cancer Res 2: 1717-1723