Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (111)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Verweij, J.
Right arrow Articles by Hansen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verweij, J.
Right arrow Articles by Hansen, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Annals of Oncology 4:673-678, 1993
© 1993 European Society for Medical Oncology

research-article

Phase I and pharmacokinetics study of topotecan, a new topoisomerase I inhibitor

J. Verweij1,, B. Lund2, J. Beijnen3, M. de Boer-Dennert1, I. Koier4, H. Rosing3 and H. Hansen2

1Dept. of Medical Oncology, Rotterdam Cancer Institute Rotterdam, The Netherlands
2Dept. of Oncology, Rigshospitalet Copenhagen, Denmark
3Dept. of Pharmacy, Slotervaart Hospital and Netherlands Cancer Institute Amsterdam
4EORTC New Drug Development Office Amsterdam, The Netherlands

Correspondence to: J. Verweij, MD, PhD, Dept. of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands

Purpose: A phase I study with topotecan (SKF 104864-A, NSC 609699), a semisynthetdc analog of camptothecin, was performed using a daily-times-5 regimen, given i.v. q 3 weeks, to evaluate the pharmacokinetics and toxicities of the compound.

Patients and methods: Patients with a histologically confirmed diagnosis of a solid tumor no longer amenable to established forms of treatment were eligible for the study. Topotecan was given as a 30 min. infusion daily on 5 successive days, repeated every three weeks. In subsequent patient cohorts the dose was escalated from 0.5 to 1.5 mg/m2/ day. Weekly evaluations included hematology and biochemistry. Response to treatment was assessed every 2 cycles. Pharmacokinetics were performed using a HPLC method.

Results: Forty-eight patients were entered. The maximal tolerated dose was 1.5 mg/m2day. The dose limiting toxicity was leucocytopenia. Other major toxicities were alopecia and moderate nausea/vomiting. Partial remissions were observed in one patient with pretreated small-cell lung cancer, one with non-small-cell lung cancer and one with no-pretreated pancreatic cancer, lasting 130–240 days. Pharmacokinetics showed a t1/2({alpha}) of 8.1 ± 7.6 min, t1/2(ß) of 132 ± 48 min, Vd, ss 72.7 ± 26.9 L/m2 and Clwt, of 0.57 ± 0.16 L/min/m2.

Conclusion: Topotecan is an interesting new topoisomerase I inhibitor exerting antitumor activity in this phase I trial. Leucocytopenia is dose-limiting. The recommended dose for phase II studies is 1.5 mg/m2/day for 5 consecutive days every 3 weeks.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
N. Masubuchi, R. D. May, and R. Atsumi
A Predictive Model of Human Myelotoxicity Using Five Camptothecin Derivatives and the In vitro Colony-Forming Unit Granulocyte/Macrophage Assay
Clin. Cancer Res., October 1, 2004; 10(19): 6722 - 6731.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. C. Daw, V. M. Santana, L. C. Iacono, W. L. Furman, D. R. Hawkins, P. J. Houghton, J. C. Panetta, A. J. Gajjar, and C. F. Stewart
Phase I and Pharmacokinetic Study of Topotecan Administered Orally Once Daily for 5 Days for 2 Consecutive Weeks to Pediatric Patients With Refractory Solid Tumors
J. Clin. Oncol., March 1, 2004; 22(5): 829 - 837.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
D. K. Armstrong
Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity
Oncologist, February 1, 2004; 9(1): 33 - 42.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. J. Guarino, C. J. Schneider, S. S. Grubbs, D. D. Biggs, A. L. Himelstein, K. Hogaboom, and S. Tilak
A Dose-Escalation Study of Weekly Topotecan, Cisplatin, and Gemcitabine Front-Line Therapy in Patients with Inoperable Non-Small Cell Lung Cancer
Oncologist, December 1, 2002; 7(6): 509 - 515.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
R. Morris and A. Munkarah
Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer
Oncologist, October 1, 2002; 7(90005): 29 - 35.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. M.F. Kruijtzer, J. H. Beijnen, H. Rosing, W. W. ten Bokkel Huinink, M. Schot, R. C. Jewell, E. M. Paul, and J. H.M. Schellens
Increased Oral Bioavailability of Topotecan in Combination With the Breast Cancer Resistance Protein and P-Glycoprotein Inhibitor GF120918
J. Clin. Oncol., July 1, 2002; 20(13): 2943 - 2950.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. L. Furman, C. F. Stewart, M. Kirstein, J. L. Kepner, M. L. Bernstein, F. Kung, T. J. Vietti, C. P. Steuber, D. L. Becton, S. Baruchel, et al.
Protracted Intermittent Schedule of Topotecan in Children With Refractory Acute Leukemia: A Pediatric Oncology Group Study
J. Clin. Oncol., March 15, 2002; 20(6): 1617 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. L. Clarke-Pearson, L. Van Le, T. Iveson, C. W. Whitney, P. Hanjani, G. Kristensen, J. H. Malfetano, R. A. Beckman, G. A. Ross, S. R. Lane, et al.
Oral Topotecan as Single-Agent Second-Line Chemotherapy in Patients With Advanced Ovarian Cancer
J. Clin. Oncol., October 1, 2001; 19(19): 3967 - 3975.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
S. Guichard, A. Montazeri, E. Chatelut, I. Hennebelle, R. Bugat, and P. Canal
Schedule-dependent Activity of Topotecan in OVCAR-3 Ovarian Carcinoma Xenograft: Pharmacokinetic and Pharmacodynamic Evaluation
Clin. Cancer Res., October 1, 2001; 7(10): 3222 - 3228.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. C. Zamboni, D. Z. D'Argenio, C. F. Stewart, T. MacVittie, B. J. Delauter, A. M. Farese, D. M. Potter, N. M. Kubat, D. Tubergen, and M. J. Egorin
Pharmacodynamic Model of Topotecan-induced Time Course of Neutropenia
Clin. Cancer Res., August 1, 2001; 7(8): 2301 - 2308.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. E. Royce, P. M. Hoff, P. Dumas, Y. Lassere, J. J. Lee, J. Coyle, M. P. Ducharme, R. De Jager, and R. Pazdur
Phase I and Pharmacokinetic Study of Exatecan Mesylate (DX-8951f): A Novel Camptothecin Analog
J. Clin. Oncol., March 1, 2001; 19(5): 1493 - 1500.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. K. Rowinsky, T. R. Johnson, C. E. Geyer Jr, L. A. Hammond, S. G. Eckhardt, R. Drengler, L. Smetzer, J. Coyle, J. Rizzo, G. Schwartz, et al.
DX-8951f, a Hexacyclic Camptothecin Analog, on a Daily-Times-Five Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies
J. Clin. Oncol., September 17, 2000; 18(17): 3151 - 3163.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Gelderblom, W. J. Loos, J. Verweij, M. J. A. de Jonge, and A. Sparreboom
Topotecan Lacks Third Space Sequestration
Clin. Cancer Res., April 1, 2000; 6(4): 1288 - 1292.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
I. F. Pollack, M. Erff, D. Bom, T. G. Burke, J. T. Strode, and D. P. Curran
Potent Topoisomerase I Inhibition by Novel Silatecans Eliminates Glioma Proliferation in Vitro and in Vivo
Cancer Res., October 1, 1999; 59(19): 4898 - 4905.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
V. M.M. Herben, R. van Gijn, J. H.M. Schellens, M. Schot, J. Lieverst, M. J.X. Hillebrand, N. E. Schoemaker, M. G. Porro, J. H. Beijnen, and W. W. ten Bokkel Huinink
Phase I and Pharmacokinetic Study of a Daily Times 5 Short Intravenous Infusion Schedule of 9-Aminocamptothecin in a Colloidal Dispersion Formulation in Patients With Advanced Solid Tumors
J. Clin. Oncol., June 1, 1999; 17(6): 1906 - 1906.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. J. H. Gerrits, J. H. M. Schellens, H. Burris, J. R. Eckardt, A. S. T. Planting, M. E. L. van der Burg, G. I. Rodriguez, W. J. Loos, V. van Beurden, I. Hudson, et al.
A Comparison of Clinical Pharmacodynamics of Different Administration Schedules of Oral Topotecan (Hycamtin)
Clin. Cancer Res., January 1, 1999; 5(1): 69 - 75.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J.-F. Héron
Topotecan: An Oncologist's View
Oncologist, December 1, 1998; 3(6): 390 - 402.
[Abstract] [Full Text]

Home page
 The OncologistHome page
D. Armstrong and S. O'Reilly
Clinical Guidelines for Managing Topotecan-Related Hematologic Toxicity
Oncologist, February 1, 1998; 3(1): 4 - 10.
[Abstract] [Full Text]

Home page
 J Oncol Pharm PractHome page
V. Relias and J. Andrew Skirvin
Review : Topoisomerase I inhibitors: 1. Topotecan
Journal of Oncology Pharmacy Practice, December 1, 1997; 3(4): 173 - 185.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.