Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

Autor: Madan RA; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Karzai FH; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Al Harthy M; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Petrylak DP; Yale School of Medicine, New Haven, CT, USA., Kim JW; Yale School of Medicine, New Haven, CT, USA., Arlen PM; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Rosner I; Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA., Theoret MR; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Cordes L; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Bilusic M; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Peer CJ; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Dawson NA; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA., Couvillon A; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Hankin A; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Williams M; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Chun G; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Owens H; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Marte JL; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Lee MJ; Developmental Therapeutics Branch, NCI, Bethesda, MD, USA., Tomita Y; Developmental Therapeutics Branch, NCI, Bethesda, MD, USA., Yuno A; Developmental Therapeutics Branch, NCI, Bethesda, MD, USA., Trepel JB; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Lee S; Developmental Therapeutics Branch, NCI, Bethesda, MD, USA., Steinberg SM; Biostatistics and Data Management Section, Center for Cancer Research, NCI, Bethesda, MD, USA., Gulley JL; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Figg WD; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA., Dahut WL; Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: BJU international [BJU Int] 2021 Apr; Vol. 127 (4), pp. 435-444. Date of Electronic Publication: 2020 Oct 23.
DOI: 10.1111/bju.15227
Abstrakt: 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.)
Databáze: MEDLINE
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