While the interval of QoL assessment may potentially be a culprit, other possible causes should be considered carefully before such statements are made. To explain the failure of zoledronic acid to improve QoL, it will help to first review the side-effects of zoledronic acid. In the placebo-controlled trial by Saad et al., zoledronic acid was associated with more fatigue, anemia, fever, myalgia, vomiting, dizziness, edema, anorexia and weight loss than was placebo [2]. These inflammatory reactions are not unexpected with nitrogen-containing bisphosphonates. It is possible that, for a particular patient, these side-effects more profoundly determine the QoL than does the presence or absence of SREs, especially if QoL measurement is conducted close to the infusion time. Moreover, since SREs occurred in only 248 patients, the remaining 392 patients without SRE, who might have experienced symptoms (solely from zoledronic acid treatment), could report a significant deterioration in QoL, eventually translating into the failure of zoledronic acid to improve QoL for the overall patient population.
Even if more frequent assessments might demonstrate an improvement in QoL, clinicians should still consider whether this is meaningful for patients. What is the merit of a treatment if it can improve QoL by less than 3 monthsthe interval of measurement used by Saad and colleagues? A serious consideration, in addition, will need to be made in the case of zoledronic acid, an exorbitant drug that has been associated with end-stage renal failure and excruciating osteonecrosis of the jaws [4]. In my opinion, perhaps the most important finding from the study by Weinfurt and colleagues [1
] is the fact that it is the psychosocial domains of the QoL, not only the physical, that decline with the occurrence of SREs. Better care of these men therefore might be derived from ensuring adequate psychosocial support, not only during clinical trials, but also in general. To date, while over 30 randomized trials on psychosocial interventions have been published for breast cancer, only four are listed for prostate cancer in the Medline database.
Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
* E-mail: tanvety{at}pol.net
References
1. Weinfurt KP, Li Y, Castel LD et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005; 16: 579584.
2. Saad F, Gleason DM, Murray R et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 14581468.
3. Bernhard J. Timing of quality of life assessment in cancer clinical trials: fine tuning remains a challenge. Ann Oncol 2005; 16: 523524.
4. Prescribing information. Zometa (zoledronic acid). Available online at www.zometa.com (26 March 2005, date accessed).
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