Drug intelligence / Profile preview

topotecan + paclitaxel + carboplatin

Development stage
Phase 3
Lead developer
Sarah Cannon Research Institute
Modality
Small Molecules
Administration
Intravenous
01

Overview

A three-drug chemotherapy combination of the small-molecule cytotoxics topotecan, paclitaxel, and carboplatin, studied primarily in epithelial ovarian cancer. Topotecan is a topoisomerase I inhibitor that stabilizes the cleavable complex between topoisomerase I and DNA, causing single-strand DNA breaks and replication-associated double-strand breaks leading to apoptosis. Paclitaxel is a taxane that promotes microtubule polymerization and prevents depolymerization, arresting cells in mitosis. Carboplatin is a platinum compound that forms DNA intra- and interstrand crosslinks, inhibiting DNA replication and transcription and inducing apoptosis. Randomized phase III evidence found no overall survival or progression-free survival advantage for adding topotecan to standard paclitaxel/carboplatin in advanced ovarian cancer, with increased severe or life-threatening adverse events reported in the triplet arm in one study. The regimen has been evaluated for feasibility and toxicity in clinical trials for previously untreated and recurrent ovarian cancer.

Other names
TPC regimenpaclitaxel/carboplatin/topotecan
02

Targets

DNATOP1 (DNA Topoisomerase I)TUBB (Tubulin (alpha and beta subunits))

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