1. Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.
- Author
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Madan RA, Karzai FH, Al Harthy M, Petrylak DP, Kim JW, Arlen PM, Rosner I, Theoret MR, Cordes L, Bilusic M, Peer CJ, Dawson NA, Couvillon A, Hankin A, Williams M, Chun G, Owens H, Marte JL, Lee MJ, Tomita Y, Yuno A, Trepel JB, Lee S, Steinberg SM, Gulley JL, Figg WD, and Dahut WL
- Subjects
- Aged, Aged, 80 and over, Anilides adverse effects, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Docetaxel adverse effects, Humans, Male, Middle Aged, Neoplasm Metastasis, Prednisone adverse effects, Prostatic Neoplasms, Castration-Resistant pathology, Pyridines adverse effects, Treatment Outcome, Anilides administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Docetaxel administration & dosage, Prednisone administration & dosage, Prostatic Neoplasms, Castration-Resistant drug therapy, Pyridines administration & dosage
- Abstract
Objective: To evaluate the safety and efficacy of cabozantinib combined with docetaxel., Patients and Methods: This was a phase 1/2 multicentre study in patients with metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (75 mg/m
2 every 3 weeks with daily prednisone 10 mg) was combined with escalating doses of daily cabozantinib (20, 40 and 60 mg). Based on the results of the phase 1 study, the investigation was expanded into a randomized study of docetaxel with prednisone (hereafter 'docetaxel/prednisone') plus the maximum tolerated dose (MTD) of cabozantinib compared with docetaxel/prednisone alone., Results: A total of 44 men with mCRPC were enrolled in this phase 1/2 trial. An MTD of 40 mg cabozantinib plus docetaxel/prednisone was determined. Dose-limiting toxicities were neutropenic fever and palmar-plantar erythrodysesthesia, and there was one death attributable to a thromboembolic event. In addition, grade 3 or 4 myelosuppression, hypophosphataemia and neuropathy were seen in three or more patients. In the phase 1 study, the median time to progression (TTP) and overall survival (OS) time were 13.6 and 16.3 months, respectively. In the phase 2 study, which was terminated early because of poor accrual, the median TTP and OS favoured the combination (n = 13) compared to docetaxel/prednisone alone (n = 12; 21.0 vs 6.6 months; P = 0.035 and 23.8 vs 15.6 months; P = 0.072, respectively)., Conclusion: Despite the limited number of patients in this study, preliminary data suggest that cabozantinib can be safely added to docetaxel/prednisone with possible enhanced efficacy., (Published 2020. This article is a US Government work and is in the public domain in the USA.)- Published
- 2021
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