INTRODUCTION: Long-term safety and tolerance is paramount when treating women who are otherwise healthy after the primary adjuvant therapy of breast cancer. Efficacy and limited safety results of a large-scale clinical trial, using adjuvant oral clodronate to prevent bone metastases in primary breast cancer patients, have been reported previously, demonstrating a reduction in the rate of bone metastases during treatment. Here we present expanded safety and tolerability results for clodronate treatment from this trial (cut-off date extended from June 1997 to June 2000). STUDY DESIGN AND METHODS: For this randomised, double-blind, placebocontrolled, multicentre study, patients were enrolled and randomised to receive oral clodronate (Bonefos) 1600 mg/day or placebo for 2 years. The total median treatment period plus follow-up was 5.5 years. Adverse events (AEs) and laboratory parameters were followed up regularly for the total study period. The 95% CIs were estimated for the difference in the rate of AEs between the treatment groups. PATIENTS: A total of 1079 women with primary operable breast cancer were enrolled to the study; 538 receivedclodronate and 541 received placebo. RESULTS:Overall incidence of AEs (96.5% of the patients) was the same in both treatment groups, although gastrointestinal disorders were significantly more frequent in the clodronate group during the total study period (66% vs 56.2%; 95% CI 4.0-15.6; p < 0.05). This was mainly due to an increase in non-severe diarrhoea beginning 3-4 months after treatment start. Serious AEs (SAEs) were reported for 39.4% of the patients receiving clodronate and 44.5% of those receiving placebo; no drug-related (clodronate or placebo) SAEs were identified. Clodronate significantly lowered mortality (98 deaths vs 129 deaths; hazard ratio 0.77; 95% CI 0.59-1.00; p = 0.047) reducing the risk of death over the total study period by 23%. AEs caused 58 early discontinuations (five drug-related events) in the clodronate group and 43 discontinuations (three drug-related events) in the placebo group. CONCLUSION: These results indicate that in women with early breast cancer receivingadjuvant systemic therapy, oral clodronate for 2 years is generally well tolerated with no serious long-term sequelae, providing a safe, long-term therapy in the adjuvant setting.
RCT Entities:
INTRODUCTION: Long-term safety and tolerance is paramount when treating women who are otherwise healthy after the primary adjuvant therapy of breast cancer. Efficacy and limited safety results of a large-scale clinical trial, using adjuvant oral clodronate to prevent bone metastases in primary breast cancerpatients, have been reported previously, demonstrating a reduction in the rate of bone metastases during treatment. Here we present expanded safety and tolerability results for clodronate treatment from this trial (cut-off date extended from June 1997 to June 2000). STUDY DESIGN AND METHODS: For this randomised, double-blind, placebocontrolled, multicentre study, patients were enrolled and randomised to receive oral clodronate (Bonefos) 1600 mg/day or placebo for 2 years. The total median treatment period plus follow-up was 5.5 years. Adverse events (AEs) and laboratory parameters were followed up regularly for the total study period. The 95% CIs were estimated for the difference in the rate of AEs between the treatment groups. PATIENTS: A total of 1079 women with primary operable breast cancer were enrolled to the study; 538 received clodronate and 541 received placebo. RESULTS: Overall incidence of AEs (96.5% of the patients) was the same in both treatment groups, although gastrointestinal disorders were significantly more frequent in the clodronate group during the total study period (66% vs 56.2%; 95% CI 4.0-15.6; p < 0.05). This was mainly due to an increase in non-severe diarrhoea beginning 3-4 months after treatment start. Serious AEs (SAEs) were reported for 39.4% of the patients receiving clodronate and 44.5% of those receiving placebo; no drug-related (clodronate or placebo) SAEs were identified. Clodronate significantly lowered mortality (98 deaths vs 129 deaths; hazard ratio 0.77; 95% CI 0.59-1.00; p = 0.047) reducing the risk of death over the total study period by 23%. AEs caused 58 early discontinuations (five drug-related events) in the clodronate group and 43 discontinuations (three drug-related events) in the placebo group. CONCLUSION: These results indicate that in women with early breast cancer receiving adjuvant systemic therapy, oral clodronate for 2 years is generally well tolerated with no serious long-term sequelae, providing a safe, long-term therapy in the adjuvant setting.
Authors: E McCloskey; P Selby; D de Takats; J Bernard; M Davies; J Robinson; R Francis; J Adams; K Pande; M Beneton; T Jalava; E Löyttyniemi; J A Kanis Journal: Bone Date: 2001-03 Impact factor: 4.398
Authors: Trevor Powles; Sandy Paterson; John A Kanis; Eugene McCloskey; Sue Ashley; Alwynne Tidy; Kirsi Rosenqvist; Ian Smith; Lars Ottestad; Sandra Legault; Marjo Pajunen; Auli Nevantaus; Esa Männistö; Anne Suovuori; Sari Atula; Jaakko Nevalainen; Liisa Pylkkänen Journal: J Clin Oncol Date: 2002-08-01 Impact factor: 44.544
Authors: P C de Groen; D F Lubbe; L J Hirsch; A Daifotis; W Stephenson; D Freedholm; S Pryor-Tillotson; M J Seleznick; H Pinkas; K K Wang Journal: N Engl J Med Date: 1996-10-03 Impact factor: 91.245
Authors: Brent O'Carrigan; Matthew Hf Wong; Melina L Willson; Martin R Stockler; Nick Pavlakis; Annabel Goodwin Journal: Cochrane Database Syst Rev Date: 2017-10-30
Authors: Trevor Powles; Alexander Paterson; Eugene McCloskey; Phil Schein; Bobbi Scheffler; Alwynne Tidy; Sue Ashley; Ian Smith; Lars Ottestad; John Kanis Journal: Breast Cancer Res Date: 2006-03-15 Impact factor: 6.466