Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054).
OBJECTIVE
Zibotentan (ZD4054) is a specific endothelin A receptor antagonist in clinical development for the treatment of hormone-resistant prostate cancer (HRPC). In a Phase II trial in patients with pain-free or mildly symptomatic metastatic HRPC, zibotentan was well tolerated with a promising signal for prolonged overall survival compared with placebo. As part of this trial, the impact of zibotentan compared with placebo on health-related quality of life (HRQoL) was assessed.


METHODS
Patients were randomized to receive once-daily oral zibotentan 10 or 15 mg, or matching placebo. Patients were allocated to one of two questionnaires; the Functional Assessment of Cancer Therapy-Prostate (FACT-P) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), supplemented by PR25, specific for prostate cancer. Questionnaires were completed at baseline and every 4 weeks until disease progression when study treatment was discontinued.


RESULTS
Compliance with questionnaire completion was >90% (286 of 312 patients) of the intention-to-treat population at baseline. Of baseline completers who were available for assessment (i.e., had not clinically progressed), 89% (164 of 184) and 83% (73 of 88) completed questionnaires at 12 and 24 weeks, respectively. HRQoL scores from both questionnaires were high at baseline and remained high throughout the study, with scores being similar in the zibotentan and placebo groups. However, some floor and ceiling effects were seen in the EORTC QLQ-C30 questionnaire.


CONCLUSIONS
High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program.
Dawson
Nancy
N
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Payne
Heather
H
University College Hospital, London, UK.
Battersby
Clare
C
AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TF, UK. clare.battersby@astrazeneca.com.
Taboada
Maria
M
AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TF, UK.
James
Nick
N
School of Cancer Sciences, University of Birmingham, Birmingham, UK.
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D019008:Drug Resistance, Neoplasm; D065130:Endothelin A Receptor Antagonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000523:psychology*; D011759:Pyrrolidines / Q000627:therapeutic use*; D011788:Quality of Life; D011795:Surveys and Questionnaires
D000970:Antineoplastic Agents; D065130:Endothelin A Receptor Antagonists; D011759:Pyrrolidines; C511404:ZD4054
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