Phase II evaluation of topotecan for pediatric central nervous system tumors

Blaney, Susan M.; Phillips, Peter C.B.; Packer, Roger J.; Heideman, Richard L.; Berg, Stacey L.; Adamson, Peter C.; Allen, Jeffrey C.; Sallan, Stephen E.; Jakacki, Regina I.; Lange, Beverly J.; Reaman, Gregory H.; Horowitz, Marc E.; Poplack, David G.; Balis, Frank M.

doi:10.1002/(sici)1097-0142(19960801)78:3<527::aid-cncr21>3.0.co;2-#

Cited by 55 publications

(11 citation statements)

References 12 publications

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“…When topoisomerase I is blocked, the DNA strands break and then cancerous cells die. TPT exhibits great activity against human ovarian cancer, cervical and small cell lung cancer (Blaney et al, 1996;Motl et al, 2006;Drummond et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Shi

Wan

et al. 2013

Biomedical Chromatography

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Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs.

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Section: Introductionmentioning

confidence: 99%

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Shi

Wan

et al. 2013

Biomedical Chromatography

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“…The antitumor activity of topotecan is S-phase-specific and prolonged drug exposure, using a daily lowdose schedule of administration, provides optimal antitumor activity [3,4]. Preclinical and pharmacokinetic studies of topotecan have demonstrated good activity against human brain tumor xenografts, and high cerebrospinal fluid (CSF) penetration providing sound rationale for its use in pediatric brain tumor trials [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Objective responses were seen in retinoblastoma with central nervous system (CNS) metastasis, ependymoma, and rhabdomyosarcoma [12]. At least three additional phase II stud-ies of topotecan in refractory or high-risk pediatric CNS tumors have been reported [6,13,14]. In either 24 or 72-hr intravenous infusions, there were some patients who experienced periods of stable disease (SD), and in fractionated (daily × 10 days) intravenous, pharmacokinetically guided dosing, objected responses were observed.…”

Section: Introductionmentioning

confidence: 99%

A phase II study of metronomic oral topotecan for recurrent childhood brain tumors

Minturn

Janss

Fisher

et al. 2010

Pediatric Blood & Cancer

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“…Two phase II studies of topotecan in children with refractory or high-risk CNS tumors have also been performed [42,43]. Topotecan was inactive in patients with glioblastoma multiforme, brain stem glioma, and medulloblastoma following administration as either a 24-hour CIVI every 3 weeks or a 72-hour CIVI every 3 weeks.…”

Section: Phase II Topotecan Single-agent Studiesmentioning

confidence: 99%

The Development of Camptothecin Analogs in Childhood Cancers

2001

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Camptothecin analogs, agents that target the intranuclear enzyme topoisomerase I, represent a promising new class of anticancer drugs for the treatment of childhood cancer. In preclinical studies, camptothecins, such as topotecan and irinotecan, are highly active against a variety of pediatric malignancies including neuroblastomas, rhabdomyosarcomas, gliomas, and medulloblastomas.In this paper, we review the status of completed and ongoing clinical trials and pharmacokinetic studies of camptothecin analogs in children. These and future planned studies of this novel class of cytotoxic agents are critical to defining the ultimate role of topoisomerase I poisons in the treatment of childhood cancer. The Oncologist 2001;6:506-516

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Phase II evaluation of topotecan for pediatric central nervous system tumors

Abstract: Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblastomas, and brain stem tumors.

Cited by 55 publications

References 12 publications

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

A phase II study of metronomic oral topotecan for recurrent childhood brain tumors

The Development of Camptothecin Analogs in Childhood Cancers

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