|Chemical and physical data|
|Molar mass||881.98 g/mol|
|3D model (JSmol)|
|(what is this?)|
Tesetaxel is an orally administered taxane being investigated as a chemotherapy agent for various types of cancer, including breast cancer, gastric cancer, colorectal cancer, and other solid tumors. It differs from other members of the taxane class (e.g. paclitaxel or docetaxel) in that it is administered orally, not intravenously.
The first preclinical studies for tesetaxel were carried out prior to 2003 both in vitro and in vivo. In both in vitro and in vivo efficacy studies, tesetaxel exhibited stronger cytotoxicity than paclitaxel and docetaxel against various tumor cell lines, especially against P-glycoprotein (P-gp)-expressing tumor cells.
In vitro, tesetaxel’s average growth inhibition of 50% (GI50) showed that it was about 20 times more effective than paclitaxel and 5 times more effective than docetaxel in 6 human tumor cell lines expressing P-glycoprotein (P-gp). In 6 different P-gp positive human tumor cell lines with drug-induced resistance, tesetaxel exhibited a 10- to 100-fold greater cytotoxicity than paclitaxel and docetaxel.
In vivo, tesetaxel exhibited significant growth-inhibitory effects (IR>90%) on P-gp-positive colon cancer DLD-1 and breast cancer DU4475 xenografts, on which neither docetaxel nor paclitaxel was effective (their IR values ranged from 26% to 58%).
Odonate Therapeutics, Inc. is conducting an approximately 600-patient, multinational, multicenter, randomized, open-label, parallel Phase 3 study, known as CONTESSA that will compare tesetaxel (27 mg/m² on the first day of a 21-day cycle) plus a reduced dose of capecitabine (1,650 mg/m²/day on days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m²/day on days 1-14 of a 21-day cycle) in patients with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive locally advanced metastatic breast cancer (MBC) previously treated with a taxane in the neoadjuvant (prior to surgery) or adjuvant (immediately following surgery) setting. CONTESSA’s primary endpoint is progression-free survival (PFS). CONTESSA’s secondary endpoints are overall survival (OS), objective response rate (ORR), disease control rate (DCR) and patient reported outcomes (PROs).
- Clinical trial number NCT01221870 for "Tesetaxel as First-line Therapy for Metastatic Breast Cancer" at ClinicalTrials.gov
- Evans, T.; Dobrila, R.; Berardi, R.; Sumpter, K.A.; Wall, L.R.; Oyama, R. (June 2006). "A phase II study of DJ-927 as second-line therapy in patients (pts) with advanced gastric cancer (GC) who have failed a 5-FU non taxane based regimen". Journal of Clinical Oncology.
- Clinical trial number NCT00080834 for "DJ-927 as Second-Line Therapy in Treating Patients With Progressive Locally Advanced or Metastatic Colorectal Adenocarcinoma" at ClinicalTrials.gov
- Clinical trial number NCT01315431 for "A Study of Tesetaxel Plus Capecitabine in Patients With Solid Tumors" at ClinicalTrials.gov
- Shionoya, Motoko; Jimbo, Takeshi; Kitagawa, Mayumi; Soga, Tsunehiko; Tohgo, Akiko (2003). "DJ-927, a novel oral taxane, overcomes P-glycoprotein-mediated multidrug resistance in vitro and in vivo". Cancer Science. 94 (5): 459–466. doi:10.1111/j.1349-7006.2003.tb01465.x.
- Yared, Jean A.; Tcakzul, Katherine HR (2012). "Update on taxane development: new analogs and new formulations". Drug Design, Development and Therapy. 6: 371–384. doi:10.2147/DDDT.S28997.
- Clinical trial number NCT03326674 for "Tesetaxel Plus Reduced Dose of Capecitabine vs. Capecitabine in HER2 Negative, HR Positive, MBC (CONTESSA) (CONTESSA)" at ClinicalTrials.gov