Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk, locally advanced prostate cancer

Abstract

BACKGROUND: Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high‐risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP). METHODS: Thirty‐one patients with high‐risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b‐3 or serum prostate‐specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER‐2/neu was performed on prechemotherapy and postchemotherapy prostate tissue. RESULTS: The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty‐nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI. CONCLUSIONS: No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity. Cancer 2009. © 2009 American Cancer Society.

Phase II Trial of Neoadjuvant Docetaxel and CG1940/CG8711 Followed by Radical Prostatectomy in Patients With High-Risk Clinically Localized Prostate Cancer

“…Although no pathological complete responses were obtained, four of the six patients had a downstaging in their Gleason sum by pathologic review of their RP specimen compared with their biopsy specimen. The absence of a pT0 in this study is similar to those of other neoadjuvant studies evaluating docetaxel, gefitinib, and mitoxantrone [7][8][9][10]. Some suggest that absence of pT0 in a patient is due to the fact that the optimal dose and duration of neoadjuvant agents remain to be optimized [10].…”

“…The absence of a pT0 in this study is similar to those of other neoadjuvant studies evaluating docetaxel, gefitinib, and mitoxantrone [7][8][9][10]. Some suggest that absence of pT0 in a patient is due to the fact that the optimal dose and duration of neoadjuvant agents remain to be optimized [10]. Prior studies evaluating neoadjuvant hormonal ablation prior to RP demonstrated significant pathologic downstaging yet failed to demonstrate meaningful improvement in biochemical recurrence (BCR) [11].…”

Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study

“…docetaxel. 22 Neoadjuvant ketoconazole and docetaxel chemotherapy has been reported to achieve 36% of PSA-free survival, 23 which showed no remarkable improvement compared with the previous literatures.…”

NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways

“…Erlotinib, a selective tyrosine kinase inhibitor for EGFR, has reported benefits in prostate cancer patients in clinical studies [10]. However, administration of gefitinib alone, another EGFR inhibitor, is ineffective and combined administrations of gefitinib and radiation therapy or docetaxel have limited therapeutic effects [26][27][28]. The combination Protein levels were detected by Western blot analysis.…”