© 2004 by Oxford University Press
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© 2004 Oxford University Press
CORRESPONDENCE |
Re: A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
Affiliations of authors: London Regional Cancer Centre, London, Ontario, Canada (EW); Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada (SB)
Correspondence to: Eric Winquist, MD, MSc, FRCP(C) FACP, London Regional Cancer Centre, 790 Commissioners Road East, London, Ontario, Canada N6A 4L6 (e-mail: eric.winquist{at}lrcc.on.ca)
The results of the well-conducted trial by Saad et al. (1) have prompted many to consider routine use of zoledronic acid to reduce the incidence of skeletal-related events in minimally symptomatic or asymptomatic men with hormone-refractory prostate cancer. This is a somewhat troublesome proposition, because all men in this situation are not at risk of a skeletal-related event. In the placebo arm of the trial (1), the rate of skeletal-related events was 44.2%, and thus more than half the men participating in the trial never experienced a skeletal-related event. Higher rates of fatigue, anemia, myalgia, fever, lower limb edema, dizziness, and weight loss were reported by men who received zoledronic acid than by men who received placebo. Thus, there is a good rationale for avoiding this treatment in men at little risk for a skeletal-related event.
Uni- and multivariable analyses of baseline patient characteristics and treatment received are usually included in reports of large, randomized trials. Typically these analyses identify independent predictors of the primary outcome and adjust the treatment effect for chance imbalances in these predictors, increasing the precision of the treatment effect (2). Compared with men who received placebo, men who received zoledronic acid at 4 mg had fewer prior skeletal-related events (30.8% versus 37.5%) and had longer median survival (546 days versus 464 days), suggesting subtle differences between these groups at baseline that may have influenced the observed rates of skeletal-related events (3,4). Even small differences in important predictors can have a major impact if the variable is important enough (2). Little is known about predictors of skeletal-related events in men with hormone-refractory prostate cancer, but clearly such information could help clinicians identify those patients at highest risk for a skeletal-related event and those most likely to benefit from zoledronic acid therapy (5). We request that the authors provide these data to help clinicians determine the most logical use of this drug for their patients.
NOTES
S. Berry has served on advisory boards and received speaking honoraria from Novartis (makers of zoledronic acid).
REFERENCES
1 Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458–68.
2 Hauck WW, Anderson S, Marcus SM. Should we adjust for covariates in nonlinear regression analyses of randomized trials? Control Clin Trials 1998;19:249–56.[CrossRef][Web of Science][Medline]
3 van Staa TP, Leufkens HG, Cooper C. Does a fracture at one site predict later fractures at other sites? Osteoporos Int 2002;13:624–9.[CrossRef][Web of Science][Medline]
4 Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 2002;168:1005–7.[CrossRef][Web of Science][Medline]
5 Berruti A, Dogliotti L, Bitossi R, Fasolis G, Gorzegno G, Bellina M, et al. Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000;164:1248–53.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2004 96: 1183-1184.
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