Related Experiment Video
Updated: Jan 24, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with
Elisabeth Heath1, Lance Heilbrun2, Heather Mannuel3
1Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA heathe@karmanos.org.
Lessons Learned:
The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate-resistant prostate cancer (mCRPC).The negative data underscore that, despite a sound biological rationale and supportive early-phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge.
Background:
Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor-induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Methods:
This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy-naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6-month progression-free survival (PFS) rate between the two arms. Secondary endpoints included 6-month overall survival (OS), objective tumor and prostate-specific antigen (PSA) response rates, biomarkers, and adverse events.
Results:
The 6-month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6-month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL-6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm).
Conclusion:
Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.
Insights
Adding cediranib to docetaxel plus prednisone did not improve outcomes for metastatic castrate-resistant prostate cancer (mCRPC) patients. The combination therapy showed no significant efficacy benefit and increased toxicity, indicating it is not a viable treatment option.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Vascular Endothelial Growth Factor (VEGF) signaling inhibition is a therapeutic strategy to constrain tumor growth.
- Cediranib, a VEGF receptor tyrosine kinase inhibitor, showed preliminary safety and efficacy when combined with docetaxel and prednisone (DP) in metastatic castrate-resistant prostate cancer (mCRPC).
Purpose of the Study:
- To evaluate if adding cediranib to the DP regimen improves efficacy in chemotherapy-naive mCRPC patients.
- To compare progression-free survival (PFS) at 6 months between the DP+cediranib and DP-only arms.
Main Methods:
- A multicenter, randomized phase II trial was conducted.
- Patients received either docetaxel, prednisone, plus cediranib (DP+C) or docetaxel plus prednisone (DP) alone.
- Primary endpoint was 6-month PFS; secondary endpoints included overall survival, response rates, biomarkers, and adverse events.
Main Results:
- The 6-month PFS rate was numerically higher in the DP+C arm (61%) versus the DP arm (57%), but not statistically significant.
- No significant differences were observed in overall survival, tumor response, or PSA response rates between the arms.
- Increased baseline interleukin-6 (IL-6) levels correlated with higher progression risk, and neutropenia was more frequent in the DP+C arm.
Conclusions:
- Combining cediranib with docetaxel and prednisone did not demonstrate superior efficacy compared to docetaxel and prednisone alone in mCRPC patients.
- The combination therapy resulted in added toxicity, specifically increased neutropenia.
- Further investigation of this combination for mCRPC is not supported by these findings.
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