Background: Docetaxel prednisone is a standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), and plasma vascular endothelial growth factor (VEGF) levels are a poor prognostic factor in this population; therefore, we evaluated the combination of docetaxel prednisone with pazopanib, an oral VEGF receptor inhibitor, for safety and preliminary efficacy.
Methods: This is a two-site phase 1b Department of Defense Prostate Cancer Clinical Trials Consortium trial of docetaxel, prednisone, and pazopanib once daily and ongoing androgen deprivation therapy and prophylactic pegfilgrastim in men with mCRPC. The primary endpoint was safety and the determination of a maximum tolerated dose (MTD) through a dose-escalation and expansion design; secondary endpoints included progression-free and overall survival (OS), prostate specific antigen (PSA) declines, radiographic responses, and pharmacokinetic and plasma angiokine biomarker analyses.
Results: Twenty-five men were treated over six dose levels. Pegfilgrastim was added to the regimen after myelosuppression limited dose escalation. With pegfilgrastim, our target MTD of docetaxel 75 mg/m q3 weeks; prednisone 10 mg daily; and pazopanib 800 mg daily was reached. Eleven additional patients were accrued at this dose level for a total of 36 patients. Dose-limiting toxicities included neutropenia, syncope, and hypertension. Three deaths attributed to study treatment occurred. The objective response rate was 31%; median PFS was 14.1 months (95% confidence interval [CI]: 7.1 and 22.2); and OS was 18.6 months (95% CI: 11.8 and 22.2).
Conclusions: The combination of docetaxel, prednisone, and pazopanib (with pegfilgrastim) was tolerable at full doses and demonstrated promising efficacy in a relatively poor risk patients with mCRPC. Further development of predictive biomarkers may enrich for patients who receive clinical benefit from this regimen.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/pros.23899 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Survival outcomes of apalutamide as a starting treatment: impact in real-world patients with metastatic hormone sensitive prostate cancer (OASIS).
Prostate Cancer Prostatic Dis
December 2024
Advent Health Urology Denver, 850 Harvard Avenue, Denver, CO, 80210, USA.
Background: Androgen receptor pathway inhibitors (apalutamide [APA], enzalutamide [ENZ], abiraterone acetate plus prednisone [AAP]) combined with androgen-deprivation therapy (ADT) are effective life-prolonging treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the impact of upfront therapy for mHSPC on outcomes in real-world clinical practice in the United States.
Methods: This retrospective, observational cohort study used electronic healthcare records from the ConcertAI RWD 360 Prostate Cancer Dataset.
Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.
Lancet
November 2024
Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.
Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe.
Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.
Eur Urol
January 2025
McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address:
Background And Objective: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.
Methods: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024.
Outcomes of First-Line Abiraterone Acetate or Enzalutamide for Older Adults With Metastatic Castration-Resistant Prostate Cancer According to Use of Upfront Docetaxel for Metastatic Castration-Sensitive Prostate Cancer in an International Multicenter Registry: A SPARTACUSS-Meet-URO 26 Study.
Clin Genitourin Cancer
October 2024
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address:
Article Synopsis
- Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged 75 and older is difficult due to limited research, but common first-line treatments include abiraterone acetate plus prednisone (AA) and enzalutamide (Enza).
- A study analyzed 337 patients aged 75+ who started AA or Enza and found no significant differences in survival rates or adverse effects between those who previously used docetaxel (D) and those who only received androgen deprivation therapy (ADT).
- The results imply that elderly men with mCRPC can expect similar outcomes and side effect profiles from AA or Enza, irrespective of prior D treatment, though the study's retrospective nature
Apatinib manifests an unexpectedly favorable outcome in the management of axillary lymph node follicular dendritic cell sarcoma: a case report.
Front Oncol
June 2024
Graduate Institute, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
We present a case of follicular dendritic cell sarcoma in the axillary lymph node, which unexpectedly showed favorable outcomes after the application of apatinib. Follicular Dendritic Cell Sarcoma (FDCS) exhibits a rare incidence and an unclear pathogenic mechanism, contributing to the limited breakthroughs in its treatment to date within the medical field. The current mainstream therapeutic approaches include surgery, CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone), ICE(ifosfamide, carboplatin, etoposide), ABVD(doxorubicin, bleomycin, vinblastine, dacarbazine), and immune checkpoint inhibitors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!