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

被引：9

作者：

Madan, Ravi A. ^{[1
]}

Karzai, Fatima H. ^{[1
]}

Al Harthy, Munjid ^{[1
]}

Petrylak, Daniel P. ^{[2
]}

Kim, Joseph W. ^{[2
]}

Arlen, Philip M. ^{[1
]}

Rosner, Inger ^{[3
]}

Theoret, Marc R. ^{[1
]}

Cordes, Lisa ^{[1
]}

Bilusic, Marijo ^{[1
]}

Peer, Cody J. ^{[1
]}

Dawson, Nancy A. ^{[4
]}

Couvillon, Anna ^{[1
]}

Hankin, Amy ^{[1
]}

Williams, Moniquea ^{[1
]}

Chun, Guin ^{[1
]}

Owens, Helen ^{[1
]}

Marte, Jennifer L. ^{[1
]}

Lee, Min-Jung ^{[5
]}

Tomita, Yusuke ^{[5
]}

Yuno, Akira ^{[5
]}

Trepel, Jane B. ^{[1
]}

Lee, Sunmin ^{[5
]}

Steinberg, Seth M. ^{[6
]}

Gulley, James L. ^{[1
]}

Figg, William D. ^{[1
]}

Dahut, William L. ^{[1
]}

机构：

[1] NCI, Genitourinary Malignancies Branch, Bldg 10,CRC 3-2571, Bethesda, MD 20892 USA

[2] Yale Sch Med, New Haven, CT USA

[3] Walter Reed Natl Mil Med Ctr, Ctr Prostate Dis Res, Bethesda, MD USA

[4] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA

[5] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA

[6] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

BJU INTERNATIONAL | 2021年 / 127卷 / 04期

关键词：

prostate cancer; metastatic prostate cancer; chemotherapy; combination therapy; #PCSM; #ProstateCancer; #uroonc; PHASE-III; DOUBLE-BLIND; TRIAL; SURVIVAL; PHARMACOKINETICS; BEVACIZUMAB; THERAPY;

D O I：

10.1111/bju.15227

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：435 / 444

页数：10

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