Phase I trial with weekly EO9, a novel bioreductive alkylating indoloquinone, by the EORTC Early Clinical Study Group (ECSG)

Cancer Chemotherapy and Pharmacology

Volumn 45, Issue 1, 2000, Pages 85-88

  Aamdal, S ^a   Lund, B ^b   Koier, I ^c   Houten, M ^c   Wanders, J ^c   Verweij, J ^d  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b Mental Health Services CPH   (Denmark)

^c EORTC New Drug Development Office   (Netherlands)

^d ERASMUS MC CANCER INSTITUTE   (Netherlands)

Author keywords

EO9 weekly; Phase I

Indexed keywords

5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; ALKYLATING AGENT; INDOLE DERIVATIVE;

ADULT; ANEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW TOXICITY; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL TUMOR; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE CALCULATION; FEMALE; FEVER; HEADACHE; HUMAN; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MALE; MAXIMUM PERMISSIBLE DOSE; MELANOMA; NAUSEA; NEPHROTOXICITY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEINURIA; SARCOMA; SOLID TUMOR; STOMACH CARCINOMA; THROMBOCYTOPENIA; UTERUS CARCINOMA; VOMITING;

EID: 0033975257     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/PL00006748     Document Type: Article

References (22)

1. 1. Belinsky M, Jaiswal AK (1993) NAD(P)H: quionone oxidoreductase 1 (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev 12: 103
2. 2. Collard J, Matthew AM, Double JA, Bibby MC (1995) EO9 relationship between DT-diaphorase levels and response in vitro and in vivo. Br J Cancer 71: 1199
3. 3. Cummings J, Spanswick VJ, Gardiner J, Ritchie A, Smyth JF (1998) Pharmacological and biochemical determinants of the antitumour activity of the indoloquinone EO9. Biochem Pharmacol 1: 55-253
4. 4. Dirix LY, Tonnesen F, Cassidy J, Epelbaum R, ten Bokkel Huinink WW, Pavlidis N, Sorio R, Gamucci T, Wolff I, Te Velde A, Lan J, Verweij J (1996) EO9 phase II study in advanced breast, gastric, pancreatic and colorectal carcinoma by EORTC Early Clinical Studies Group. Eur J Cancer 32A: 2019
5. 5. Fitzsimmons SA, Workman P, Grever M, Paull K, Camalier R, Lewis AD (1996) Reductase enzyme expression across the National Cancer Institute tumor cell line panel: correlation with sensitivity to mitomycin C and EO9. J Natl Cancer Inst 88: 259
6. 6. Hendriks HR, Pizao PE, Berger DP, Kooistra KL, Bibby MC, Boven E, Dreef-van der Meulen, Henrar RE, Fiebig HH, Double JA, Hornstra HW, Pinedo HM, Workman P, Schwartsmann G (1993) EO9: a novel bioreductive alkylating indoloquionone with preferential solid tumor activity and lack of bone marrow toxicity in preclinical models. Eur J Cancer 29: 879
7. 7. Jaffar M, Naylor MA, Robertson N, Stratford IJ (1998) Targeting hypoxia with a new generation of indoloquinones. Anticancer Drug Des 13: 593
8. 8. Kuin A, Aalders M, Lamfers M, van Zuidam DJ, Essers M, Beijnen JH, Smets LA (1999) Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG). Br J Cancer 79: 793
9. 9. McLeod HL, Graham MA, Aamdal S, Setanoians A, Groot Y, Lund B, on behalf of the EORTC (1996) Phase I pharmacokinetics and limited sampling strategies for the bioreductive alkylating drug EO9. Early Clinical Trials Group Eur J Cancer 32A: 1518
10. 10. Oostveen EA, Speckamp WN (1987) Mitomycin C analoges 1. Indoloquinones as potential bisalkylating agents. Tetrahedron 43: 255.
11. 11. Pavlidis N, Hanauske AR, Gamucci T, Smyth J, Lehnert M, te Velde A, Lan J, Verweij J (1996) A randomized phase II study with two schedules of the novel indoloquinione EO9 in non-small cell lung cancer: a study of the EORTC Early Clinical Studies Group (ECSG). Ann Oncol 7: 529
12. 12 a. Plumb JA, Gerritsen M, Milroy R, Thomson P, Workman P (1994) Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines. Int J Radiat Oncol Biol Phys 15: 295
13. 12 b. Plumb JA, Workman P (1994) Unusually marked hypoxic sensitization to indoloquinone EO9 and mitomycin C in a human colon-tumour cell line that lacks DT-diaphorase activity. Int J Cancer 56: 134
14. 13. Rauth AM, Melo T, Misra V (1998) Bioreductive therapies: an overview of drugs and their mechanisms of action. Int J Radiat Oncol Biol Phys 42: 755
15. 14. Riley RJ, Workman P (1992) DT-diaphorase and cancer therapy. Cancer Metastasis Rev 12: 3
16. 15. Robertson N, Stratford IJ, Houlbrook S, Carmichael J, Adams GE (1992) The sensitivity of human tumour cells to quinone bioreductive drugs: what role for DT-diaphorase? Biochem Pharmacol 44: 409
17. 16. Robertson N, Haigh A, Adams GE, Stratford IJ (1994) Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia. Eur J Cancer 30A: 1013
18. 17. Schellens JH, Planting AS, van Acker BA, Loos WJ, de Boer-Dennert M, van der Burg ME, Koier I, Krediet RT, Stoter G, Verweij J (1994) Phase I and pharamacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug EO9. J Natl Cancer Inst 86: 906
19. 18. Smitskamp-Wilms E, Giaccone G, Pinedo HM, van der Laan BFAM, Peters GJ (1995) DT-diaphorase activity in normal and neoplastic human tissues; an indicator for sensitivity to bioreductive agents ? Br J Cancer 72: 917
20. 19. Verweij J, Aamdal S, Schellens J, Koier I, Lund B (1994) Clinical studies with EO9, a new indoloquinone bioreductive alkylating cytotoxic agent. EORTC Early Clinical Trials Group. Oncol Res 6: 519
21. 20. Walton MI, Bibby MC, Double JA, Plumb JA, Workman P (1992) DT-diaphorase activity correlates with sensitivity to the indoloquinone EO9 in mouse and human colon carcinomas. Eur J Cancer 28A: 1597
22. 21. Workman P (1994) Enzyme-directed bioreductive drug development revisited: a commentary on recent progress and future prospects with emphasis on quinone anticancer agents and quinone metabolizing enzymes, particularly DT-diaphorase. Oncol Res 6: 461