Sagopilone, a microtubule stabilizer for the potential treatment of cancer.
Sagopilone (ZK-EPO), under development by Bayer Schering Pharma AG, is a novel, fully synthetic epothilone B analog that is representative of a new class of microtubule-stabilizing agents that have a similar mechanism of action to taxanes, but have a decreased propensity for drug resistance. In preclinical studies, sagopilone inhibited cell growth in a wide range of human cancer cell lines. Moreover, sagopilone was not recognized by multidrug-resistant (MDR) cellular efflux mechanisms, and maintained its activity in MDR tumor models. Phase I clinical trials established that the sagopilone side-effect profile was similar to that reported for taxanes, with neuropathy and neutropenia being the most commonly reported toxicities. Initial reports revealed that sagopilone was clinically active in advanced ovarian cancer, advanced melanoma and metastatic chemotherapy-naïve castration-resistant prostate cancer. In contrast, clinical activity demonstrated by sagopilone in NSCLC or metastatic breast cancer was similar to, or less than, the clinical activity observed with other, more clinically advanced epothilones. At the time of publication, sagopilone was being investigated in a broad phase II clinical trial program, including in patients with glioblastoma, NSCLC, melanoma, and small-cell lung, prostate, ovarian and breast cancers.
Galmarini
Carlos M
CM
UMR 5239, UFR de Médicine Lyon-Sud, 165 Chemin du Grand Revoyet, BP 12, 69921 Oullins, France. cmgalma@hotmail.com
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone