Daniel George

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in Surgery

Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1992

Duke University

Medical Resident, Medicine

Johns Hopkins University

Fellow in Medical Oncology, Medicine

Johns Hopkins University

Grants:

Plasma Angiome and Serum Androgens as Predictors of Overall Survival in Metastatic Prostate Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Collaborator
Start Date
End Date

Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Collaborating Investigator
Start Date
End Date

Disparities in the Use of Oral Anticancer Agents in Kidney Cancer

Administered By
Population Health Sciences
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

Calithera CX-839-008

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Phase II open-label, Multicenter study of Apalutamide, Abiraterone Acetate and Prednisone in African American and Caucasian men with metastatic castrate-resistant prostate cancer

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

genitourinary tumours, non prostate Phase III trial of sunitinib (SU) vs placebo (PBO) as adjuvant treatment for high-risk renal cell carcinoma (RCC) after nephrectomy (S-TRAC)

Authors
Ravaud, A; Motzer, RJ; Pandha, HS; Staehler, M; George, D; Pantuck, AJ; Patel, A; Chang, YH; Escudier, B; Donskov, F; Magheli, A; Carteni, G; Laguerre, B; Tomczak, P; Breza, J; Gerletti, P; Lin, X; Lechuga, M; Martini, JF; Patard, JJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1241485
Source
scopus
Published In
Annals of Oncology
Volume
27
Published Date
Start Page
vi565
DOI
10.1093/annonc/mdw435.22

Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial.

BACKGROUND: This phase 1/2 study assessed sunitinib combined with docetaxel (Taxotere) and prednisone in chemotherapy-naive metastatic, castration-resistant prostate cancer (mCRPC) patients. PATIENTS AND METHODS: To determine the recommended phase 2 dose (RP2D), 25 patients in four dose escalation cohorts received 3-week cycles of sunitinib (2 weeks on, 1 week off), docetaxel and prednisone, preceded by a 4-week sunitinib 50 mg/day lead in. RP2D was evaluated in 55 additional patients. The primary end point was prostate-specific antigen (PSA) response rate. RESULTS: One phase 1 dose-limiting toxicity occurred (grade 3 hyponatremia). The RP2D was sunitinib 37.5 mg/day, docetaxel 75 mg/m2 and prednisone 5 mg b.i.d. During phase 2, confirmed PSA responses occurred in 31 patients [56.4% (95% confidence interval 42.3-69.7)]. Median time to PSA progression was 9.8 months. Forty-one patients (75%) were treated >3 months, 12 (22%) completed the study (16 cycles) and 43 (78%) discontinued (36% for disease progression and 27% adverse events). The most frequent treatment-related grade 3/4 adverse events were neutropenia (53%; 15% febrile) and fatigue/asthenia (16%). Among 33 assessable patients, 14 (42.4%) had confirmed partial response. Median progression-free and overall survivals were 12.6 and 21.7 months, respectively. CONCLUSION: This combination was moderately well tolerated, with promising response rate and survival benefit, justifying further investigation in mCRPC.
Authors
Zurita, AJ; George, DJ; Shore, ND; Liu, G; Wilding, G; Hutson, TE; Kozloff, M; Mathew, P; Harmon, CS; Wang, SL; Chen, I; Chow Maneval, E; Logothetis, CJ
MLA Citation
Zurita, A. J., et al. “Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial.Ann Oncol, vol. 23, no. 3, Mar. 2012, pp. 688–94. Pubmed, doi:10.1093/annonc/mdr349.
URI
https://scholars.duke.edu/individual/pub1431953
PMID
32018662
Source
pubmed
Published In
Ann Oncol
Volume
23
Published Date
Start Page
688
End Page
694
DOI
10.1093/annonc/mdr349

Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.

Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs: HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells.
Authors
Bakthavatsalam, S; Wiangnak, P; George, DJ; Zhang, T; Franz, KJ
MLA Citation
Bakthavatsalam, Subha, et al. “Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.Bioorg Med Chem Lett, vol. 30, no. 11, June 2020, p. 127148. Pubmed, doi:10.1016/j.bmcl.2020.127148.
URI
https://scholars.duke.edu/individual/pub1436721
PMID
32253061
Source
pubmed
Published In
Bioorg Med Chem Lett
Volume
30
Published Date
Start Page
127148
DOI
10.1016/j.bmcl.2020.127148

Concurrent or layered treatment with radium-223 and enzalutamide or abiraterone/prednisone: real-world clinical outcomes in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: In this study, we evaluated real-world data on radium-223 plus abiraterone/prednisone or enzalutamide. Previously, the ERA 223 trial (NCT02043678) demonstrated increased fracture risk with concurrent treatment with radium-223 and abiraterone plus prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We used the Flatiron Health database to perform a retrospective study of patients with mCRPC treated with radium-223. Treatment with radium-223 plus abiraterone/prednisone or enzalutamide was defined as concurrent if both drugs started within 30 days of one another, or layered when the second drug started ≥30 days after the first. The index date was defined as the day of the first radium-223 dose. Outcome measures included symptomatic skeletal events (SSEs), overall survival (OS), and patterns of treatments received. RESULTS: Of the 625 patients treated with radium-223, 22% received it together with abiraterone/prednisone and 27% with enzalutamide. When these agents were combined, they were often initiated in a layered fashion (73% layered, 23% concurrent). Prior or concomitant bone health agents (BHAs) were received by 67% and 55% of patients, respectively. Median follow-up was 9 months. Overall, incidence rates for SSEs and pathologic fractures were 0.35 and 0.11 patients per person-year, respectively. Median OS from mCRPC diagnosis was 28.1 months. CONCLUSIONS: In this real-world setting, combination treatments with radium-223 and abiraterone/prednisone or enzalutamide were common. These agents were more commonly given in a layered than a concurrent fashion. Incidence rates for SSEs were reduced when BHAs were used; however, BHAs were underutilized.
Authors
Shore, N; Higano, CS; George, DJ; Sternberg, CN; Saad, F; Tombal, B; Miller, K; Kalinovsky, J; Jiao, X; Tangirala, K; Sartor, O
URI
https://scholars.duke.edu/individual/pub1441298
PMID
32404868
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-020-0236-0

Influence of diabetes and congestive heart failure (CHF) on selection of first-line (1L) treatment for metastatic renal cell carcinoma (mRCC)

Authors
Gong, J; George, D; Mhatre, S; Lin, SW; Surinach, A; Wallen, H; Vohra, R; Simpson, J; Ogale, S; Pal, SK
MLA Citation
Gong, J., et al. “Influence of diabetes and congestive heart failure (CHF) on selection of first-line (1L) treatment for metastatic renal cell carcinoma (mRCC).” Annals of Oncology, vol. 27, 2016, p. vi282. Scopus, doi:10.1093/annonc/mdw373.37.
URI
https://scholars.duke.edu/individual/pub1251078
Source
scopus
Published In
Annals of Oncology
Volume
27
Published Date
Start Page
vi282
DOI
10.1093/annonc/mdw373.37