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)

Abstract

Purpose: 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.

Keywords: EORTC QLQ-C30; FACT-P; Health-related quality of life (HRQoL); Hormone-resistant prostate cancer (HRPC); Zibotentan.

Fig. 1

FACT-P and EORTC questionnaire allocation and completion. Footnote * number of patients remaining in study, available to complete questionnaire. Completion data are expressed as evaluable/expected, where expected forms = one at baseline, one at withdrawal, and one for each time interval a patient entered, and evaluable forms = forms with at least one subscale that can be determined

Fig. 2

FACT-P trial outcome index over the course of the study. Footnote trial outcome index is a composite score comprising physical well-being + functional well-being + prostate cancer subscale

Fig. 3

Representative FACT-P scores over the course of the study a physical well-being; b prostate cancer subscale

Fig. 4

Representative EORTC scores over the course of the study a physical functioning; b treatment-related symptoms