© 2004 European Society for Medical Oncology
Reply to Letter to the Editor on "The efficacy and safety of oral ibandronate in the treatment of metastatic bone disease in patients with breast cancer", by G. Utkan, A. Büyükçelik, B. Yalç
n (Ann Oncol 2004; 15: 1574)
In response to Dr Utkan and colleagues [1
] regarding the mortality incidence we reported with oral ibandronate in a 2-year phase III trial [2], the actual number of deaths was very small (16 in the placebo group compared with 23 in the ibandronate 20 mg and 50 mg groups). Most deaths were due to disease progression, and none were attributed to treatment. The number of events was insufficient to find a statistically significant difference between the groups. Survival was not a primary end point in this trial of patients with established skeletal metastases; in fact, a survival benefit has not been seen with any bisphosphonates in metastatic bone disease using Cochrane review methodology [3]. However, the benefits of bisphosphonates overall in reducing skeletal events and morbidity are now strong enough for them to be uniformly recommended in destructive bone metastases [4]. The clodronate studies referred to by Utkan et al. [5,6] were conducted in the adjuvant patient setting, where improved survival is one of the main aims of bisphosphonate therapy. Atula et al. [6] found only a borderline survival benefit (P=0.047) of clodronate in breast cancer patients, based on multiple regression analyses of a small number of events. Another long-term randomized trial failed to support these results [7], and clodronate was actually associated with a worse mortality rate. Ibandronate, a highly potent bisphosphonate with anti-tumor efficacy [8], may offer enhanced protection for patients at risk of bone metastases. The results of ongoing adjuvant trials using several bisphosphonates are eagerly awaited.
University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8852, USA
* ); Email: debu.tripathy{at}utsouthwestern.edu
References
1. Utkan G, Büyükçelik A, Yalç
n B. The efficacy and safety of oral ibandronate in the treatment of metastatic bone disease in patients with breast cancer (Letter to the Editor). Ann Oncol 2004; 15: 1574.
2. Tripathy D, Lichinitzer M, Lazarev A et al. Oral ibandronate for the treatment of metastatic bone disease in breast cancer: efficacy and safety results from a randomized, double-blind, placebo-controlled trial. Ann Oncol 2004; 15: 743–750.
3. Pavlakis N, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2002; 1: CD003474.
4. Hillner BE, Ingle JN, Chlebowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003; 21: 4042–4057.
5. Dearnaley DP, Sydes MR, Mason MD et al. A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PRO Trial). J Natl Cancer Inst 2003; 95: 1300–1311.
6. Atula S, Powles T, Paterson A et al. Extended safety profile of oral clodronate after long-term use in primary breast cancer patients. Drug Saf 2003; 26: 661–671.[CrossRef][Medline]
7. Saarto T, Blomqvist C, Virkkunen P, Elomaa I. Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial. J Clin Oncol 2001; 19: 10–17.
8. Fromigue O, Lagneaux L, Body JJ. Bisphosphonates induce breast cancer cell death in vitro. J Bone Miner Res 2000; 15: 2211–2221.[CrossRef][Web of Science][Medline]
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  D. Tripathy Reply to Letter to the Editor on "The efficacy and safety of oral ibandronate in the treatment of metastatic bone disease in patients with breast cancer", by G. Utkan, A. Buyukcelik, B. Yalcyn (Ann Oncol 2004; 15: 1574) Ann. Onc., October 1, 2004; 15(10): 1574 - 1575. [Full Text] [PDF]
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