Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.
BJU Int
; 127(4): 435-444, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-32969563
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/m2 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pyridines
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Prednisone
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Antineoplastic Combined Chemotherapy Protocols
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Prostatic Neoplasms, Castration-Resistant
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Docetaxel
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Anilides
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Antineoplastic Agents
Type of study:
Clinical_trials
Limits:
Aged
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Aged80
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Humans
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Male
/
Middle aged
Language:
En
Journal:
BJU Int
Journal subject:
UROLOGIA
Year:
2021
Type:
Article
Affiliation country:
United States