Randomized Phase II Study of Two Doses of Gefitinib in Hormone-Refractory Prostate Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group

Canil, Christina; Moore, Malcolm J.; Winquist, Eric; Baetz, Tara; Pollak, Michael; N., Kim; Berry, Scott; Ernst, D. Scott; Douglas, L.; Brundage, Michael; Fisher, B.; McKenna, Anne; Seymour, Lesley

doi:10.1200/jco.2005.02.129

Cited by 187 publications

(109 citation statements)

References 21 publications

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“…Since this trial was designed and completed, reports of gefitinib alone in metastatic and nonmetastatic castratory hormone progressive prostate cancer have found no responses (as defined as PSA declines). [23][24][25][26] In addition, there were no responses to the combination of docetaxel and gefitinib compared with the treatment of docetaxel alone. 26 Furthermore, although there were no changes in the pharmacokinetics of docetaxel combined with 250 mg of gefitinib, at a higher dose, the area under the curve concentration for docetaxel was reduced by 20%.…”

Section: Discussionmentioning

confidence: 99%

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

Vuky

Porter

Isacson

et al. 2009

Cancer

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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.

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Section: Discussionmentioning

confidence: 99%

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

Vuky

Porter

Isacson

et al. 2009

Cancer

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“…5,15 Previous studies have used the FACT-P to evaluate QoL in patients with prostate cancer undergoing external beam radiotherapy, 16 brachytherapy, 16,17 surgery, 16 cryosurgery, 18,19 chemotherapy 20 and treatment with an epidermal growth factor receptor inhibitor. 21 These studies have reported significant changes in health-related QoL in response to the various anti-cancer treatments.…”

Section: Quality Of Life In Prostate Cancermentioning

confidence: 99%

Measuring the individual quality of life of patients with prostate cancer

Stone

Matar

et al. 2008

Prostate Cancer Prostatic Dis

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Prostate cancer can have diverse effects on patients' quality of life (QoL). Standard QoL questionnaires do not address all of the concerns expressed by such patients. The primary purpose of this study was to identify those issues with the greatest influence on the QoL of patients with prostate cancer. A secondary aim was to compare the performance of the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) semi-structured interview with the Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P). A mixed population of patients with prostate cancer (including those with localized and metastatic disease) completed the SEIQoL-DW and the FACT-P. The SEIQoL-DW was satisfactorily completed by 180 patients, including 93 patients with metastatic disease. Patients identified 144 separate QoL concerns, and these were then independently grouped by three of the authors into 13 distinct themes. The most frequently identified themes were 'leisure and hobbies', 'family' and 'health'. The themes that patients considered to be the most important were 'partner/spouse', 'family' and 'health'. Patients were most satisfied with their QoL in the domains of 'family', 'partner/spouse' and 'friends'. They were least satisfied with 'sexuality', 'mobility' and 'psychological factors'. Patients with metastatic disease rated their QoL significantly (Po0.0001) lower than other patients using the FACT-P, but not using the SEIQoL-DW (P ¼ 0.07). Patients with prostate cancer identified numerous QoL concerns that are not included (or are underrepresented) in standard health-related QoL questionnaires such as the FACT-P. Health-related QoL questionnaires may underestimate the QoL of patients with metastatic disease.

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“…Signalling mediated through ErbB2/ErbB3 is implicated in AR activation through effects on AR DNA binding and stability (Mellinghoff et al, 2004). However, phase II studies of single agent ErbB signalling pathway inhibitors, including gefitinib (a small molecule EGFR tyrosine kinase inhibitor), trastuzumab (a monoclonal antibody to HER2) and pertuzumab (a HER2 dimerisation inhibitor) have reported no clinically significant activity in unselected CRPC patients (Ziada et al, 2004;Canil et al, 2005;de Bono et al, 2005).…”

Section: Erbb Receptorsmentioning

confidence: 99%

Improving the outcome of patients with castration-resistant prostate cancer through rational drug development

et al. 2006

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Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease.

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Randomized Phase II Study of Two Doses of Gefitinib in Hormone-Refractory Prostate Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group

Abstract: Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.

Cited by 187 publications

References 21 publications

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

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

Measuring the individual quality of life of patients with prostate cancer

Improving the outcome of patients with castration-resistant prostate cancer through rational drug development

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