This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Athale, U. H. Articles by Heideman, R. L. Search for Related Content PubMed PubMed Citation Articles by Athale, U. H. Articles by Heideman, R. L. Social Bookmarking                            What's this?

Phase I Study of Combination Topotecan and Carboplatin in Pediatric Solid Tumors

From the Departments of Hematology-Oncology, Pharmaceutical Sciences, St Jude Children’s Research Hospital, Memphis, TN; and Hospital St Justine, Montreal, Quebec, Canada.

Address reprint requests to R.L. Heideman, MD, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105; email: richard.heideman{at}stjude.org

PURPOSE: We conducted a phase I trial of escalating doses of topotecan (TOPO) in association with a fixed systemic exposure of carboplatin (CARBO) with or without granulocyte colony-stimulating factor (G-CSF) in children.

PATIENTS AND METHODS: Two separate cohorts of patients (pts) with solid tumors were studied: (A) pts with refractory or recurrent disease and (B) pts with no prior myelosuppressive therapy or newly diagnosed tumors for which there was no standard chemotherapy. CARBO was given on day 1 at an area under the curve of 6.5, followed by TOPO as a continuous infusion for 3 days; the starting dose of TOPO was 0.50 mg/m²/d. Cycles were repeated every 21 days. G-CSF was given at a dose of 5 µg/kg/d starting on day 4.

RESULTS: Forty-eight of 51 pts were assessable for toxicity. In group A, dose-limiting myelosuppression persisted despite de-escalation of TOPO to 0.3 mg/m²/d and use of G-CSF. In group B, the maximum-tolerated dose of TOPO was 0.5 mg/m²/d for 3 days, and 0.6 mg/m²/d for 3 days with G-CSF. No significant nonhematologic toxicities were observed. Among 46 pts assessable for response, one had complete response, five had partial response, and 18 had stable disease.

CONCLUSION: Although this combination possesses antineoplastic activity in pediatric solid tumors, hematologic toxicity precluded any meaningful TOPO dose escalation. The addition of G-CSF did not alter this. The potential for preservation of activity and diminution of toxicity with alternative sequences and schedules of administration (topoisomerase followed by alkylating or platinating agents) should be evaluated.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Y. Tsui, C. Dalgard, K. R. Van Quill, L. Lee, H. E. Grossniklaus, H. F. Edelhauser, and J. M. O'Brien Subconjunctival Topotecan in Fibrin Sealant in the Treatment of Transgenic Murine Retinoblastoma Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 490 - 496. [Abstract] [Full Text] [PDF]

				P. Schaiquevich, J. C. Panetta, L. C. Iacono, B. B. Freeman III, V. M. Santana, A. Gajjar, and C. F. Stewart Population Pharmacokinetic Analysis of Topotecan in Pediatric Cancer Patients Clin. Cancer Res., November 15, 2007; 13(22): 6703 - 6711. [Abstract] [Full Text] [PDF]

				Q. Yang, C. M. Kiernan, Y. Tian, H. R. Salwen, A. Chlenski, B. A. Brumback, W. B. London, and S. L. Cohn Methylation of CASP8, DCR2, and HIN-1 in Neuroblastoma Is Associated with Poor Outcome Clin. Cancer Res., June 1, 2007; 13(11): 3191 - 3197. [Abstract] [Full Text] [PDF]

				N. A. Laurie, J. K. Gray, J. Zhang, M. Leggas, M. Relling, M. Egorin, C. Stewart, and M. A. Dyer Topotecan Combination Chemotherapy in Two New Rodent Models of Retinoblastoma Clin. Cancer Res., October 15, 2005; 11(20): 7569 - 7578. [Abstract] [Full Text] [PDF]

				J. M. Gallo, P. Vicini, A. Orlansky, S. Li, F. Zhou, J. Ma, S. Pulfer, M. A. Bookman, and P. Guo Pharmacokinetic Model-Predicted Anticancer Drug Concentrations in Human Tumors Clin. Cancer Res., December 1, 2004; 10(23): 8048 - 8058. [Abstract] [Full Text] [PDF]

				B. W. Cooper, G. J. Veal, T. Radivoyevitch, M. J. Tilby, H. J. Meyerson, H. M. Lazarus, O. N. Koc, R. J. Creger, G. Pearson, G. M. Nowell, et al. A Phase I and Pharmacodynamic Study of Fludarabine, Carboplatin, and Topotecan in Patients With Relapsed, Refractory, or High-Risk Acute Leukemia Clin. Cancer Res., October 15, 2004; 10(20): 6830 - 6839. [Abstract] [Full Text] [PDF]

				B. H. Kushner Neuroblastoma: A Disease Requiring a Multitude of Imaging Studies J. Nucl. Med., July 1, 2004; 45(7): 1172 - 1188. [Abstract] [Full Text] [PDF]

				J. L. Weinstein, H. M. Katzenstein, and S. L. Cohn Advances in the Diagnosis and Treatment of Neuroblastoma Oncologist, June 1, 2003; 8(3): 278 - 292. [Abstract] [Full Text] [PDF]

				G. Toffoli, R. Sorio, F. Sartor, L. Raffin, A. Veronesi, and M. Boiocchi Carboplatin and Topotecan Combination and Myelosuppression J. Clin. Oncol., August 15, 2002; 20(16): 3558 - 3558. [Full Text] [PDF]