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Oral paclitaxel and encequidar in patients with breast cancer: a pharmacokinetic, safety, and antitumor activity study.
Therapeutic Advances in Medical Oncology ( IF 4.9 ) Pub Date : 2023-07-21 , DOI: 10.1177/17588359231183680 Ming-Shen Dai,Ta-Chung Chao,Chang-Fang Chiu,Yen-Shen Lu,Her-Shyong Shiah,Christopher G C A Jackson,Noelyn Hung,Jianguo Zhi,David L Cutler,Rudolf Kwan,Douglas Kramer,Wing-Kai Chan,Albert Qin,Kuan-Chiao Tseng,Cheung Tak Hung,Tsu-Yi Chao
Therapeutic Advances in Medical Oncology ( IF 4.9 ) Pub Date : 2023-07-21 , DOI: 10.1177/17588359231183680 Ming-Shen Dai,Ta-Chung Chao,Chang-Fang Chiu,Yen-Shen Lu,Her-Shyong Shiah,Christopher G C A Jackson,Noelyn Hung,Jianguo Zhi,David L Cutler,Rudolf Kwan,Douglas Kramer,Wing-Kai Chan,Albert Qin,Kuan-Chiao Tseng,Cheung Tak Hung,Tsu-Yi Chao
Background
Paclitaxel is widely used for the treatment of metastatic breast cancer (MBC). However, it has a low oral bioavailability due to gut extrusion caused by P-glycoprotein (P-gp). Oral paclitaxel (oPAC) may be more convenient, less resource-intensive, and more tolerable than its intravenous form. Encequidar (E) is a first-in-class, minimally absorbed, gut-specific oral P-gp inhibitor that facilitates the oral absorption of paclitaxel.
Objectives
To investigate the pharmacokinetics (PK), overall response rate (ORR), and safety of weekly oral paclitaxel with encequidar (oPAC + E) in patients with advanced breast cancer.
Design
This is a multicenter, single-arm, open-label study in six medical centers in Taiwan.
Methods
Patients with advanced breast cancer were administered 205 mg/m2 oPAC and 12.9 mg E for 3 consecutive days weekly for up to 16 weeks. Plasma samples were collected at weeks 1 and 4. PK, ORR, and safety were evaluated.
Results
In all, 28 patients were enrolled; 27 had MBC; 23 had prior chemotherapy; and 14 had ⩾2 lines of prior chemotherapy. PK were evaluable in 25 patients. Plasma paclitaxel area under the curve (AUC)(0-52 h) at week 1 (3419 ± 1475 ng h/ml) and week 4 (3224 ± 1150 ng h/ml) were equivalent. Best overall response in 28 evaluable patients was partial response (PR) in 11 (39.3%), 13 (46.4%) stable disease (SD), and 1 (3.6%) with progressive disease (PD). No patient achieved complete response (CR). The clinical benefit rate (CR + PR + SD) was 85.7%. Major adverse events among the 28 treated patients were grade 3 neutropenia (25%), grade 4 neutropenia (18%), with febrile neutropenia in 4%, and grade 3 diarrhea (4%). No treatment-related deaths occurred. Grade 2 peripheral neuropathy occurred in 1 (4%) patient and grade 3 peripheral neuropathy in 1 (4%) patient.
Conclusions
oPAC + E produced a consistent therapeutic plasma paclitaxel exposure during treatment. There was a high rate of radiologically assessed clinical benefit, and a low rate of neurotoxicity which may provide advantages over IV paclitaxel.
Registration
ClinicalTrials.gov Identifier: NCT03165955.
更新日期：2023-07-21
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