Bisphosphonate Treatment Recommendations for Oncologists

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1 Bisphosphonate Treatment Recommendations for Oncologists Roger von Moos Rätisches Kantons- und Regionalspital, Chur, Switzerland Key Words. Bisphosphonates Ibandronate Renal safety Product labeling Product information Nephrotoxicity Abstract Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. In recent years, there has been increasing awareness about the development of bisphosphonate-induced nephrotoxicity. This has emerged mainly from increased clinical experience with zoledronic acid (Zometa ; Novartis Pharmaceuticals Corporation, East Hanover, NJ, us.novartis.com). For this reason, the U.S. and European product labels for i.v. zoledronic acid were recently updated to include additional renal safety cautions, including dose adjustment in patients with mild-to-moderate renal impairment. However, renal toxicity is not a class effect. The product label for ibandronate (Bondronat, F. Hoffmann- La Roche Ltd., Basel, Switzerland, has remained unchanged since the launch of the drug in the European Union in Ibandronate does not require mandatory monitoring of kidney function prior to each infusion. In addition, ibandronate can be used in patients with varying degrees of renal impairment. It also can be used without restrictions for nephrotoxic medications, and dose adjustment is only required in patients with severe renal impairment. Clinical implications of the renal safety of ibandronate include reducing the physician and nursing time needed for managing the adverse renal events associated with bisphosphonate therapy and dosing based on renal function. There also are no added renal safety risks and fewer inconvenient hospital visits with ibandronate therapy. In addition to i.v. ibandronate, an oral formulation of the drug is available. Oral ibandronate therapy is especially desirable because the medication is convenient (with a small, once-daily tablet that can be taken at home), reducing the health care costs associated with infusions. Clinical studies also indicate that 50 mg oral ibandronate has an efficacy similar to that of i.v. bisphosphonates and is associated with a low incidence of adverse gastrointestinal events. The Oncologist 2005;10(suppl 1):19 24 Downloaded from by guest on August 13, 2018 Introduction Bisphosphonate-induced nephrotoxicity is problematic for cancer patients and health care professionals. Clinically significant deterioration in renal function is a risk with some bisphosphonates [1, 2], requiring renal function monitoring and occasional drug discontinuation. In addition, renal impairment can progress to renal failure, prompting the need for renal dialysis and causing death in some patients. Estimates suggest that, in the U.S., approximately 7.3% of the people with pre-existing chronic kidney disease would be at a greater risk for renal deterioration during long-term bisphosphonate therapy [3]. Studies have reported renal toxicity with approved doses of i.v. zoledronic acid (Zometa ; Novartis Pharmaceuticals Corporation, East Hanover, NJ, us.novartis.com). In the adverse event reporting system of the U.S. Food and Drug Administration (FDA), 72 cases Correspondence: Roger von Moos, M.D., Rätisches Kantons- und Regionalspital, Loestrasse 170, CH-7000, Chur, Switzerland. Telephone: ; Fax: ; roger.vonmoos@scag.gr.ch Received August 1, 2005; accepted for publication August 29, AlphaMed Press /2005/$12.00/0 The Oncologist 2005;10(suppl 1):

2 20 Bisphosphonate Treatment Recommendations for Oncologists of renal dysfunction associated with zoledronic acid were identified from August 2001 to March 2003 [4]. Of the 72 patients, 27 required dialysis and 18 died. In addition, retrospective studies [5 7] have shown substantial deterioration in renal function with zoledronic acid. The studies revealed that the incidence of renal dysfunction was highest in patients with multiple myeloma [5] and those who were given pamidronate (Aredia ; Novartis Pharmaceuticals Corporation) prior to zoledronic acid therapy [7]. Because of patient safety concerns, the product label for zoledronic acid in the U.S. and European Union was updated to include additional warnings of nephrotoxicity and restrictions for patients with varying degrees of renal impairment [8, 9]. Evidence suggests that renal toxicity is not a class effect of bisphosphonates. Results of phase II/III clinical studies demonstrate that ibandronate (Bondronat ; F. Hoffmann- La Roche Ltd., Basel, Switzerland, has a renal safety profile comparable with that of placebo [10]. For this reason, it is important to understand the differences among the newer bisphosphonates and to be informed about the best practices for maintaining renal safety when treating cancer patients with bone metastases. Indications In the U.S. and Europe, zoledronic acid is indicated in conjunction with standard antineoplastic therapy for treating patients with hypercalcemia of malignancy, multiple myeloma, and bone metastases from solid tumors [8, 9]. In Europe, ibandronate is indicated for preventing skeletal events such as pathologic fractures and bone complications requiring radiotherapy or surgery in patients with breast cancer and bone metastases [11]. In addition, ibandronate is approved for treating tumor-induced hypercalcemia with or without metastases. Several clinical studies suggest that ibandronate may have pan-tumor effects. Results of a placebo-controlled trial show that i.v. ibandronate prevented skeletal events in a subset of 15 patients with colorectal cancer [12]. Research also shows that nonstandard, intensive i.v. ibandronate dosing provided rapid and sustained relief of bone pain in patients with hormone-refractory prostate cancer [13, 14] and other types of urologic cancer [15] and moderate-to-severe, opioidresistant bone pain from a variety of malignant tumors [16]. Infusion Duration and Dosage A 4-mg zoledronic acid infusion given over no fewer than 15 minutes every 3 or 4 weeks is recommended to prevent skeletal-related events in adults and elderly patients with advanced malignancies involving bone who have a creatinine clearance >60 ml/min [8, 9]. The recommended zoledronic acid doses for patients with reduced renal function are listed in Table 1. Zoledronic acid is not recommended in patients with bone metastases and severe renal impairment. Factors such as dehydration and the use of other nephrotoxic drugs that predispose patients to renal deterioration should be identified and managed if possible. The product label for ibandronate has remained unchanged since the launch of the drug in 2003 [11]. The recommended dose of ibandronate for metastatic bone disease is 6 mg infused over 1 hour every 3 4 weeks. There is no need for dose adjustment in patients with mild or moderate renal impairment (patients with a creatinine clearance 30 ml/min). In addition, ibandronate can be used in patients with severe renal impairment (i.e., those with a creatinine clearance <30 ml/min). In those patients, the dose must be reduced to 2 mg infused over 1 hour every 3 4 weeks to maintain the same drug exposure achieved with the 6-mg standard dose. There are no dosing restrictions for ibandronate in patients who also are receiving cancer therapies with nephrotoxic side effects. 15-Minute Ibandronate Infusion Results of a preliminary, parallel-group study in 57 healthy volunteers have shown that it may be possible to safely Table 1. Recommended i.v. zoledronic acid and i.v. ibandronate dosing schedules for patients with varying degrees of renal function i.v. zoledronic acid i.v. ibandronate Standard 4 mg given every mg given every 3 4 regimen weeks over 15 minutes weeks over 1 hour Mild-to- Dose adjustments No dose moderate required adjustment required Renal >60 ml/min = 4 mg impairment depending on ml/min = 3.5 mg creatinine clearance ml/min = 3.3 mg ml/min = 3.0 mg >60 ml/min = 4mg Severe renal Not recommended Below 30 ml/min impairment creatinine clearance, the dose should be reduced to 2 mg every 3 4 weeks, infused over 1 hour Renal Recommended prior to Not mandatory; function each dose at physician s monitoring discretion

3 von Moos 21 reduce the infusion time of 6 mg i.v. ibandronate from 60 minutes to 30 or 15 minutes [17]. Reducing the infusion time from 60 to 15 minutes increased the mean peak concentrations (307.9 ng/ml ± 44.8 ng/ml versus ng/ml ± 94.5 ng/ml, respectively) with no adverse effect on renal function parameters such as creatinine clearance (Fig. 1), serum creatinine levels, and markers of tubular or glomerular damage (Fig. 2) during a 3-day follow-up. Similarly, there were no reports of renal adverse events in an openlabel trial to assess the safety and effects on bone turnover of a single 15-minute infusion of 6 mg ibandronate on day 1, followed by daily oral dosing (50 mg/day) for 12 weeks in 39 patients with either breast cancer (n = 31) or multiple myeloma (n = 8) [18]. Calculated creatinine clearance levels also were similar at baseline and week 12 (Fig. 3). A comparative trial is under way to evaluate the renal safety of a 60-minute versus a 15-minute ibandronate infusion. Renal Monitoring Renal toxicity associated with i.v. bisphosphonate administration increases the use of health care resources for patient care. Managing adverse renal events, regular serum creatinine monitoring, and dosing based on renal function increase a patient s need for care, including physicians and nurses time. In addition, i.v. dosing is inconvenient for patients because it requires hospital visits. Renal monitoring guidelines in the prescribing information for zoledronic acid recommend that serum creatinine be measured before each dose of zoledronic acid. The guidelines also suggest treatment be withheld in patients with renal deterioration [8]. Although clinical studies have not shown evidence of deterioration in renal function with long-term ibandronate therapy [19], renal function should be monitored according to clinical assessment of the patient. Mandatory monitoring of renal function, however, is not required (Table 1) [11]. Oral Formulations Some patients prefer oral treatment because it can be taken as a simple, once-daily dose at home, precluding the need for regular hospital visits. Oral treatment also gives patients more control over their treatment, allowing them to include it in their daily routine. The clinical benefits of self-administration include increased availability of infusion equipment for other patients (i.e., those receiving chemotherapy). Oral bisphosphonate therapy is ideal for patients who have completed i.v. chemotherapy. Although oral clodronate (Bonefas ; Schering AG, Berlin, has been available for many years, clinical experience indicates that it is less effective than i.v. bisphosphonates [20, 21]. To achieve Figure 1. Mean creatinine clearance with 6 mg i.v. ibandronate following 60-, 30-, and 15-minute infusions in healthy volunteers [17]. Figure 2. Levels of N-acetyl-β-D-glucosaminidase (β-nag) with 6 mg i.v. ibandronate following 60-, 30-, and 15-minute infusions in healthy volunteers [17]. Figure 3. Creatinine clearance with a 15-minute infusion of 6 mg i.v. ibandronate followed by daily oral dosing (50 mg/day) in patients with bone metastases from breast cancer or multiple myeloma [18].

4 22 Bisphosphonate Treatment Recommendations for Oncologists therapeutic concentrations, oral clodronate is administered in large tablets once or twice daily at least 1 hour before food (Table 2). In a study of oral clodronate in patients with metastatic bone pain (n = 55), 11% of the patients discontinued treatment because of difficulty swallowing the capsules [22]. High incidences of adverse gastrointestinal events commonly contribute to noncompliance with oral clodronate. In an update of a 2-year breast cancer study [23, 24], the proportion of patients with adverse gastrointestinal events during the medication period was significantly higher with clodronate (1,600 mg/day) than with placebo (57.1% versus 45.3%, respectively; p <.05), and there was a significantly higher proportion of patients with diarrhea (15.1% versus 6.8%, respectively; p <.05). Monitoring patients and administering medication to treat the side effects increases health care costs and decreases the availability of hospital beds. Although oral bisphosphonates have traditionally been considered inferior in efficacy to i.v. agents, recent studies show that i.v. and oral ibandronate have similar benefits. Three phase III studies of similar design (one i.v. and two oral trials) have shown that the reduction in the risk for skeletal events in breast cancer patients given a daily, oral, 50-mg dose of ibandronate was comparable with that of 6 mg i.v. ibandronate given every 3 4 weeks [18, 25]. Similar to i.v. ibandronate, the oral formulation significantly reduced and maintained bone pain scores below baseline over 2 years of treatment and improved quality of life [25 28]. In addition, a 12-week, head-to-head, open-label trial of breast cancer patients with bone metastases demonstrated equivalent effects of oral ibandronate (50 mg/ day; n = 128) and i.v. zoledronic acid (4 mg infused over 15 minutes every 4 weeks; n = 126) on biochemical markers of bone turnover [29]. Table 2. Comparison of the characteristics of oral clodronate and oral ibandronate treatments [This table was corrected April 17, 2006.] Oral clodronate Tablet size 400 or 800 mg 50 mg Oral ibandronate Dosing regimen 1,600 mg/day 50 mg/day (800 mg/day to 3,200 mg/day maximum) Post-dose 2 hours 1 hour fasting interval In the phase III study of 50 mg oral ibandronate in breast cancer patients, the incidence of mild treatmentrelated adverse gastrointestinal events (reported by 2% of patients in any treatment group), such as abdominal pain, dyspepsia, nausea, and esophagitis, were low ( 7.0%) [26]. Oral ibandronate (50 mg) was also well tolerated in 115 patients who agreed to enter a 2-year extension phase [30]. Of the 7% of adverse events considered possibly or probably related to treatment with ibandronate, the most common were dyspepsia (2.6%), hypocalcemia (2.6%), and esophagitis (1.7%). No treatment-related adverse events led to withdrawal from the study. There were no renal adverse events or laboratory abnormalities of clinical relevance in patients receiving oral ibandronate. Ibandronate is given once daily in a small tablet (approximately 1 cm in length). In the phase III and open-label extension trials, no patients withdrew because of swallowing difficulties [26, 30]. Patients are required to fast only overnight and for a minimum of 30 minutes after taking the capsules (Table 2). Case Histories of Patients Treated with Bisphosphonates Patient A Patient A is a 64-year-old female with breast cancer and metastatic bone disease. In May 2003, she began zoledronic acid (4 mg) and received monthly infusions for 19 months. In our hospital, the average time taken for the analysis of a patient s blood sample is minutes. After calculating Patient A s creatinine clearance using the Cockroft-Gault formula, the medical team adjusted Patient A s zoledronic acid dose to reflect her actual creatinine clearance. If her renal functioning was worse, the clinician asked about any other potentially nephrotoxic prescription or overthe-counter medications she had taken. Because of the patient s concerns about her deteriorating renal function, the health care team had to reassure her that the dose change was needed because of the drug and was not due to disease progression. Although zoledronic acid provided symptom relief, patient A commented that waiting in the hospital substantially disrupted her quality of life. Patient A has type II diabetes mellitus and takes nonsteroidal anti-inflammatory drugs (NSAIDs) because of skeletal pain. With higher NSAID doses, the patient suffered from mild renal insufficiency. After reducing the NSAID dose, her renal function normalized. We decided to change the bisphosphonate to ibandronate. The patient has now received 7 doses of i.v. ibandronate in conjunction with her NSAID therapy. The patient s serum creatinine levels are within normal limits.

5 von Moos 23 Patient B Patient B, a 51-year-old woman with breast cancer, was diagnosed with bone metastases in September After receiving i.v. ibandronate, patient B was started on oral ibandronate at a dose of 50 mg/day in April At each monthly hospital visit, a blood sample is taken as part of routine clinical practice. Patient B then receives a prescription for a 3-month supply of oral ibandronate. By using oral ibandronate, there is no need for the health care team to wait for the laboratory results and adjust the patient s dose according to her creatinine clearance. Furthermore, there are no concerns about concomitant nephrotoxic medications. Oral ibandronate is very well tolerated by this patient; in particular, there have been no gastrointestinal side effects. Patient B prefers at-home self-administration over the prior i.v. infusion in the hospital setting. Conclusions Renal toxicity is not a class effect of bisphosphonates. Trials and postmarketing experience revealed renal deterioration, renal failure, and dialysis in some patients treated with zoledronic acid (including those treated with the approved 4-mg dose infused over 15 minutes) [1, 2, 4 7]. Ibandronate has a renal safety profile comparable with that of placebo. For these reasons, clinicians must be aware of differences among bisphosphonates and realize how best to maintain renal safety in patients with bone metastases who are being treated with bisphosphonates. Ibandronate s favorable renal safety profile provides several key benefits to health care professionals and patients, including no need for renal monitoring before each infusion and no dosing based on renal function in patients with mild-to-moderate renal impairment. Ibandronate also does not increase the toxicity of concomitant prescribed or over-the-counter nephrotoxic drugs. In addition, there are no added renal safety risks and complications, fewer hospital visits for renal monitoring or management of adverse events, and lower risks for discontinuing chemotherapy or bisphosphonate therapy. Studies show that it may be possible to safely reduce the infusion time for 6 mg i.v. ibandronate from 60 minutes to 30 or 15 minutes, reducing the burden of administering bisphosphonates in hospital i.v. therapy units. Confirmatory studies are under way. Oral bisphosphonate therapy can be more attractive than i.v. administration because the medication is convenient and causes no problems with renal safety factors, which decreases health care costs. Clinical studies indicate that 50 mg oral ibandronate has an efficacy similar to those of i.v. bisphosphonates and is associated with a low incidence of adverse gastrointestinal events. In i.v. and oral formulations, ibandronate provides physicians and patients with a continuum of bisphosphonate therapy that can be extended from the hospital to home. In choosing the optimal bisphosphonate, clinicians must consider drug benefits, the risks for side effects, and convenience. Although considerations differ according to each patient s needs, the favorable renal safety profile of ibandronate makes it a useful treatment option. Acknowledgments I thank Thomson Gardiner-Caldwell US for their editorial assistance. Disclosure of Potential Conflicts of Interest Dr. von Moos is a consultant for Roche and Schering Plough and has an unrestricted grant from Schering Plough. References 1 Rosen LS, Gordon D, Kaminski M et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001;7: Rosen LS, Gordon D, Kaminski M et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003;98: Balla J. The issue of renal safety of zoledronic acid from a nephrologist s point of view. The Oncologist 2005;10: ; author reply Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003;349: Johnson KB, Gable P, Kaime EM et al. Significant deterioration in renal function with the new bisphosphonate, zoledronic acid. J Clin Oncol 2003;22: Kloth DD, McDermott RS, Rogatko A et al. Impact of zoledronic acid (Zol) on renal function in patients (pts) with cancer: is constant monitoring necessary? J Clin Oncol 2003;22: Stein SH, Davidson R, Tweed A et al. Renal dysfunction with IV bisphosphonates in patients with metastatic breast cancer - University of Pennsylvania. J Clin Oncol 2003;22: Novartis Pharmaceuticals Corporation. Zometa (zoledronic acid). US summary of product characteristics. East Hanover, NJ: Novartis Pharmaceuticals Corporation, November Novartis International AG. Zometa (zoledronic acid). EU summary of product characteristics. Basel, Switzerland: Novartis International AG, May 2005.

6 24 Bisphosphonate Treatment Recommendations for Oncologists 10 Jackson GH. Renal safety of ibandronate. The Oncologist 2005;10(suppl 1): F. Hoffmann-La Roche Ltd. Bondronat (ibandronic acid). Summary of product characteristics. Basel, Switzerland: F. Hoffmann-La Roche Ltd., October Heras P, Karagiannis S, Kritikos K et al. Ibandronate is effective in preventing skeletal events in patients with bone metastases secondary to breast and colorectal cancer. Ann Oncol 2004;15(suppl 3): Heidenreich A, Elert A, Hofmann R. Ibandronate in the treatment of prostate cancer associated painful osseous metastases. Prostate Cancer Prostatic Dis 2002;5: Ohlmann C, Heidenreich A. Efficacy of ibandronate in the management of painful osseous metastases due to hormone refractory prostate cancer. Support Care Cancer 2003;11: Heidenreich A, Ohlmann C, Olbert P et al. High-dose ibandronate is effective and well tolerated in the treatment of pain and hypercalcaemia due to metastatic urologic cancer. Eur J Cancer 2003;1(suppl 5): Mancini I, Dumon JC, Body JJ. Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study. J Clin Oncol 2004;22: Neugebauer G, Köhler W, Akinkunmi L et al. Influence of peak ibandronic acid concentrations after 6-mg IV administration with shortened infusion time (15 and 30 minutes) on renal safety in man. J Clin Oncol 2001;20:122A. 18 Body JJ, Bergström B. Ibandronate is well-tolerated by 15-minute infusion in patients with metastatic bone disease from breast cancer and multiple myeloma. Breast Cancer Res Treat 2004;88(suppl 1): Diel I, Pecherstorfer M, Body JJ et al. Long-term safety of intravenous ibandronate for up to 4 years in metastatic breast cancer: an open-label trial. Support Care Cancer 2005;13: Elomaa I, Kylmala T, Tammela T et al. Effect of oral clodronate on bone pain. A controlled study in patients with metastic [sic] prostatic cancer. Int Urol Nephrol 1992;24: Jagdev SP, Purohit P, Heatley S et al. Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease. Ann Oncol 2001;12: Robertson AG, Reed NS, Ralston SH. Effect of oral clodronate on metastatic bone pain: a double-blind, placebo-controlled study. J Clin Oncol 1995;13: 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: Powles T, Paterson S, Kanis JA et al. Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 2002;20: Body JJ, Diel IJ, Lichinitser MR et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003;14: Body JJ, Diel IJ, Lichinitzer M et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br J Cancer 2004;90: Body JJ, Diel IJ, Bell R et al. Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer. Pain 2004;111: Diel IJ, Body JJ, Lichinitser MR et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. Eur J Cancer 2004;40: Body JJ, Lichinitser M, Tjulandin SA et al. Effect of oral ibandronate versus intravenous (i.v.) zoledronic acid on markers of bone resorption in patients with breast cancer and bone metastases: results from a comparative phase III trial. J Clin Oncol 2005;23(suppl 16): Bell R, Tripathy D, Bergström B. Tolerability and convenience of oral ibandronate for patients with skeletal metastases. Ann Oncol 2004;15(suppl 3):224.

7 Errata This material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Patients Previously Transfused or Treated with Epoetin Alfa at Low Baseline Hemoglobin Are at Higher Risk for Subsequent Transfusion: An Integrated Analysis of the Canadian Experience Ian Quirt, Michael Kovacs, Félix Couture, A. Robert Turner, Michael Noble, Ronald Burkes, Sean Dolan, Richard K. Plante, Catherine Y. Lau, José Chang The Oncologist 2006;11:73 82; doi: /theoncologist In Figure 3, RR was incorrectly labeled as response rate when it should have been called out as relative risk. Here we reprint the figure in its entirety. A corrected figure has been posted on Figure 3. Relative risk of subsequent transfusion was calculated as a function of baseline Hb strata relative to baseline Hb strata > 11 g/dl. (A): Relative risk of subsequent transfusion calculated in patients transfused after day 28 of epoetin alfa treatment. Patients initiating epoetin alfa therapy at a baseline Hb <10 g/dl had a RR of 2.65 (95% CI, ) of receiving subsequent transfusions compared to patients initiating therapy earlier (Hb g/dl). (B): Relative risk of subsequent transfusion calculated in patients transfused from baseline to end of study. Patients initiating epoetin alfa therapy at a baseline Hb <10 g/dl had a RR of 2.29 (95% CI, ) of receiving subsequent transfusions compared to patients initiating therapy earlier (Hb g/dl). Abbreviations: CI, confidence interval; Hb, hemoglobin; RR, Relative risk. Figure 4 was incorrectly labeled. The upper line should be labeled Baseline pre-transfusion rather than No baseline pretransfusion. Here we reprint the figure in its entirety. A corrected figure has been posted on Figure 4. Number of units of blood received by all patients and the subset of pretransfused patients during epoetin alfa treatment from day 1 to end of study as a linear function of baseline hemoglobin level. It is regrettable that Fernando Camacho, Ph.D., statistician, was not included as a co-author. His contributions and input in establishing the per-patient database and carrying out the statistical analyses were, unfortunately and inadvertently, not acknowledged in the original manuscript. Dr. Fernando Camacho should correctly have been listed as a co-author on the manuscript published in The Oncologist. The online version has been corrected in departure from print.

8 Errata This material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Bisphosphonate Treatment Recommendations for Oncologists Roger von Moos The Oncologist 2005;10(suppl 1):19 24; doi: /theoncologist Table 2 erroneously included a row labeled Renal toxicity. Here we reprint the corrected table in its entirety. A corrected table has been posted on Table 2. Comparison of the characteristics of oral clodronate and oral ibandronate treatments Oral clodronate Oral ibandronate Tablet size 400 or 800 mg 50 mg Dosing regimen 1,600 mg/day 50 mg/day (800 mg/day to 3,200 mg/day maximum) Post-dose fasting interval 2 hours 1 hour AlphaMed Press