Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer

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

Research output: Contribution to journalArticleScientificpeer-review

332 Citations (Scopus)


Purpose: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases. Patients and Methods: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity. Results: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P = .127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P = .016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P = .257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n= 129; P = .047) during the total follow-up period. Conclusion: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.

Original languageEnglish
Pages (from-to)3219-3224
Number of pages6
JournalJournal of Clinical Oncology
Issue number15
Publication statusPublished - 1 Aug 2002
Externally publishedYes
Publication typeA1 Journal article-refereed

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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