Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology

Volumn 70, Issue 2, 2012, Pages 239-250

  Trocó, Inaki F ^a   Cendrós, Josep María ^b   Soto, Elena ^a   Prunonosa, Joan ^b   Perez Mayoral, Ana ^b   Peraire, Concepción ^b   Principe, Paola ^b   Delavault, Patrick ^b   Cvitkovic, Frédérique ^c   Lesimple, Thierry ^d   Obach, Rosendo ^b  

^a UNIVERSITY OF NAVARRA   (Spain)

^b IPSEN   (France)

^c CENTRE RENÉ HUGUENIN   (France)

^d CENTRE EUGÈNE MARQUIS   (France)

Author keywords

Adverse effects; Dose finding; Elomotecan; Pharmacokinetics; Population modeling

Indexed keywords

ELOMOTECAN;

ADULT; ADVANCED CANCER; AGE DISTRIBUTION; AGED; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; CANCER PATIENT; COHORT ANALYSIS; DIARRHEA; DISEASE DURATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; SOLID TUMOR; TREATMENT RESPONSE; VOMITING;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CAMPTOTHECIN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; GENOTYPE; HUMANS; INFUSIONS, INTRAVENOUS; LEUKOCYTE COUNT; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MODELS, BIOLOGICAL; NEOPLASMS; NEUTROPHILS; TANDEM MASS SPECTROMETRY; TREATMENT OUTCOME;

EID: 84866552473     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-1906-y     Document Type: Article

References (21)

1. Bailly C (2003) Homocamptothecins: Potent topoisomerase I inhibitors and promising anticancer drugs. Crit Rev Oncol Hematol 45:91-108
2. Demarquay D, Coulomb H, Huchet M et al (2000) The homocamptothecin, BN 80927, is a potent topoisomerase I poison and topoisomerase II catalytic inhibitor. Ann N Y Acad Sci 922:301-302
3. Huchet M, Demarquay D, Coulomb H et al (2000) The dual topoisomerase inhibitor, BN 80927, is highly potent against cell proliferation and tumor growth. Ann N Y Acad Sci 922:303-305
4. Demarquay D, Huchet M, Coulomb H et al (2004) BN80927: A novel homocamptothecin that inhibits proliferation of human tumor cells in vitro and in vivo. Cancer Res 64:4942-4949
5. Lesimple T (2010) Phase I dose-finding study of BN80927 as an intravenous infusion every 21 days in patients with advanced malignant solid tumors. J Clinical Oncology 28(suppl):3072
6. Beal SL, Sheiner LB, Boeckmann A (eds) (2006) (1989-2006) NONMEM User's Guides. Icon Development Solutions, Ellicott City
7. Karlsson MO, Sheiner LB (1993) The importance of modeling interoccasion variability in population pharmacokinetic analyses. J Pharmacokinet Biopharm 21:735-750
8. Friberg LE, Henningsson A, Maas H et al (2002) Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol 20:4713-4721
9. Mandema JW, Verotta D, Sheiner LB (1992) Building population pharmacokinetic-pharmacodynamic models. I. Models for covariate effects. J Pharmacokinet Biopharm 20:511-528
10. Jonsson EN, Karlsson MO (1999) Xpose-an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Comput Methods Programs Biomed 58:51-64
11. Lindbom L, Ribbing J, Jonsson EN (2004) Perl-speaks-NONMEM (PsN)-a Perl module for NONMEM related programming. Comput Methods Programs Biomed 75:85-94
12. Bergstrand M, Hooker AC, Wallin J, Karlsson MO (2011) Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J 13:143-151
13. Sheiner LB, Stanski DR, Vozeh S et al (1979) Simultaneous modeling of pharmacokinetics and pharmacodynamics: Application to d-tubocurarine. Clin Pharmacol Ther 25:358-371
14. Hing J, Perez-Ruixo JJ, Stuyckens K et al (2007) Mechanismbased pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis) induced neutropenia. Clin Pharmacol Ther 83:130-143
15. Trocóniz IF, Garrido MJ, Segura C et al (2006) Phase I dosefinding study and a pharmacokinetic/pharmacodynamic analysis of the neutropenic response of intravenous diflomotecan in patients with advanced malignant tumours. Cancer Chemother Pharmacol 57:727-735
16. Mould DR, Holford NH, Schellens JH et al (2002) Population pharmacokinetic and adverse event analysis of topotecan in patients with solid tumors. Clin Pharmacol Ther 71:334-348
17. Xie R, Mathijssen RH, Sparreboom A et al (2002) Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Clin Pharmacol Ther 72:265-275
18. Schellens JH, Heinrich B, Lehnert M et al (2002) Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies. Invest New Drugs 20:83-93
19. Veltkamp SA, Witteveen EO, Capriati A et al (2008) Clinical and pharmacologic study of the novel prodrug delimotecan (MEN 4901/T-0128) in patients with solid tumors. Clin Cancer Res 14:7535-7544
20. Bigioni M, Parlani M, Bressan A et al (2009) Antitumor activity of delimotecan against metastatic melanoma: Pharmacokinetics and molecular determinants. Int J Cancer 125:2456-2464
21. Sparreboom A, Gelderblom H, Marsh S et al (2004) Diflomotecan pharmacokinetics in relation to ABCG2 421C[A genotype. Clin Pharmacol Ther 76:38-44