Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer

Andreopoulou, Eleni; Chen, Thomas; Liebes, Leonard; Curtin, John P.; Blank, Stephanie V.; Wallach, Rony; Hochster, Howard S.; Fm, Muggia

doi:10.1007/s00280-010-1510-y

Cited by 10 publications

(3 citation statements)

References 32 publications

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“…), sometimes the peak topotecan concentration becomes to 2.5 μM (Andreopoulou et al . ). In addition, topotecan binds to tissues, especially in the gut and kidney (Shah and Balthasar ).…”

Section: Discussionmentioning

confidence: 97%

Subunit‐dependent inhibition and potentiation of 5‐HT3 receptor by the anticancer drug, topotecan

Nakamura

Ishida

Yamada

et al. 2013

Journal of Neurochemistry

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The 5-hydroxytryptamine (serotonin, 5-HT) type 3 (5-HT3) receptor belongs to the superfamily of Cys-loop ligand-gated ion channels, and can be either homopentameric (5-HT3A) or heteropentameric (5-HT3AB) receptor. Several modulators are known, which either inhibit or potentiate this channel, but few have any appreciable selectivity between the two subtypes or can modulate one receptor differently to the other. In this study, we show that the anticancer drug, topotecan, bidirectionally modulates the 5-HT3 receptor using a two-electrode voltage clamp technique. Topotecan inhibited 5-HT-gated current through homomeric 5-HT3A receptors.Interestingly, however, additional expression of the 5-HT3B subunit changed the response to topotecan dramatically from an inhibitory to a potentiatory one. This effect was dependent on the level of 5-HT3B subunit expression. Moreover, the effect was reduced in the receptors containing the 5-HT3B (Y129S) polymorphic variant. These finding could explain individual differences in the sensitivity to topotecan-induced nausea and vomiting.

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“…), sometimes the peak topotecan concentration becomes to 2.5 μM (Andreopoulou et al . ). In addition, topotecan binds to tissues, especially in the gut and kidney (Shah and Balthasar ).…”

Section: Discussionmentioning

confidence: 97%

Subunit‐dependent inhibition and potentiation of 5‐HT3 receptor by the anticancer drug, topotecan

Nakamura

Ishida

Yamada

et al. 2013

Journal of Neurochemistry

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“…Primary CD4 + T cells were treated with 0,25; 0,5 and 25µM topotecan hydrochloride hydrate (Sigma-Aldrich) for either 3 or 7 hours and collected for cell viability assay or fixed for immunofluorescence (IF) staining. The different drug concentrations were chosen to include a range of different concentrations used in previous studies on different cell lines originating from different cancer types (Danks et al, 1988;Botling et al, 1994;Jonsson et al, 1997;Hassan et al, 2001) and, on the lower end, a potentially achievable level of topotecan in plasma (Andreopoulou et al, 2010). For follow-up on long term effects of topotecan, cells were washed with PBS after a 7-hour incubation with the aforementioned concentrations of the drug, kept in culture for another 72 hours and tested for cell viability.…”

Section: Drug Treatmentmentioning

confidence: 99%

“…Also, the clinical activity of topotecan was shown in cases of ovarian carcinoma (Gore et al, 1996), non-small-cell lung cancer (Perez-Soler et al, 1996) and leukemia (Kantarjian et al, 1993;Rowinsky et al, 1994). While potential side effects of topotecan on myeloid cells and thrombocytes have been reported (Andreopoulou et al, 2010), its effects on human lymphocytes is less known. In particular, we hypothesized that activation of T-lymphocytes might render them susceptible to topotecan due to the increased metabolic activity.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic Topoisomerase-I Inhibition Causes Dna Damage and Mortality in Activated Cd4+ T Cells

Stanić

Shytaj

Lušić

2018

GenApp

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Topoisomerase-I is required for DNA replication. It acts by preventing torsional stress caused by DNA winding during replication fork progression. Topoisomerase-I inhibitors are widely used in many cancer therapies, in light of their anti-proliferative activity. However, their use as chemotherapeutics is associated with significant toxicity due to the off-target effects on healthy cells. We analyzed the dose-time-toxicity profile of a clinically employed topoisomerase-I inhibitor, i.e. topotecan, on primary CD4+T cells. This cell type was chosen to model a typical in-vivo interaction, due to the wide use of topotecan in the treatment of T-cell lymphomas. Our results show that a clinically achievable concentration of topotecan can induce toxic effects in healthy CD4+ T cells as early as 7 hours of the in vitro treatment. Toxicity of the drug was markedly increased by prolonging the post-treatment follow-up, but not by increasing concentrations, suggesting that clinical doses of topotecan can induce cell death and DNA damage in non-cancerous activated CD4+ T lymphocytes.

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The role of single strand break repair pathways in cellular responses to camptothecin induced DNA damage

Mei¹,

Lei²,

Tan³

et al. 2020

Biomedicine & Pharmacotherapy

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Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer

Abstract: Topotecan IP for 3-5 days is tolerable; occasionally, myelosuppression is dose-limiting. Topotecan 1.25 mg (days 1-3) with IP cisplatin 50 mg/m(2) (day 1) is a regimen suitable for consolidation in phase 3 trials.

Cited by 10 publications

References 32 publications

Subunit‐dependent inhibition and potentiation of 5‐HT3 receptor by the anticancer drug, topotecan

Subunit‐dependent inhibition and potentiation of 5‐HT3 receptor by the anticancer drug, topotecan

Pharmacologic Topoisomerase-I Inhibition Causes Dna Damage and Mortality in Activated Cd4+ T Cells

The role of single strand break repair pathways in cellular responses to camptothecin induced DNA damage

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