The MEDLINE (OVID) (1980 through April 2002) and CANCERLIT (OVID) (1975 through March 2002) databases were searched with the following terms: "exp Multiple Myeloma" (Medical subject heading [MeSH]), "bone metastases" (text word), "bone metasta:" (text word), and "metastatic bone disease" (text word), combined with "exp Diphosphonates" (MeSH), "exp Etidronic Acid" (MeSH), "exp Alendronate" (MeSH), "exp Clodronic Acid" (MeSH), "diphosphonate" (text word), "etidronate" (text word), "etidronate disodium" (text word), "alendronate" (text word), "clodronic acid" (text word), "clodronate" (text word), "pamidronate" (text word), "zoledronate" (text word), "ibandronate" (text word), and "bisphosphonate:" (text word). These terms were then combined with the search terms for the following study designs: practice guidelines, systematic reviews, meta-analyses, randomized controlled trials, and controlled clinical trials. The Cochrane Library (Cochrane Database of Systematic Reviews (OVID) (2002, Issue 1), Cochrane Controlled Trials Register (OVID) (2002, Issue 1)) was also searched for systematic reviews or trials. In addition, the Physician Data Query (PDQ) clinical trials database on the Internet (http://www.cancer.gov/search/clinical_trials/), and conference proceedings of the American Society of Clinical Oncology (ASCO) (1997 to 2001) and American Society of Hematology (ASH) (1999 to 2001) were searched for reports of new or ongoing trials. Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials, as were the reference lists from relevant review articles.
The literature search was updated in September 2002: MEDLINE (OVID) (April 2002 through September 2002), CANCERLIT (OVID) (April 2002 through August 2002), Cochrane Database of Systematic Reviews (OVID) (2002, Issue 3), Cochrane Controlled Trials Register (OVID) (2002, Issue 3), and the ASCO 2002 meeting proceedings.
Inclusion Criteria
Articles were selected for inclusion in this systematic review of the evidence if they were fully published reports or published abstracts of any one of the following:
- Systematic reviews or practice guidelines evaluating bisphosphonate use in patients with multiple myeloma
- Randomized controlled trials (RCTs) or meta-analyses of RCTs comparing one bisphosphonate agent with another bisphosphonate or comparing a bisphosphonate with placebo or no treatment in patients with multiple myeloma
The trials were required to report on at least one of the following outcomes: overall survival, skeletal-related survival, quality of life, bone pain, pathological fractures (non-vertebral or vertebral), progression of bone disease (osteolytic lesions), or hypercalcemia. Treatment-related toxicity was also an outcome of interest. Many trials have evaluated endpoints assessing metabolic parameters of bone disease; while these outcomes may provide useful information establishing a "proof-of principle" for using bisphosphonates in patients with myeloma, these outcomes were not considered to be sufficient to determine recommendations for treatment.
Exclusion Criteria
- RCTs that included patients with various types of malignancies in which the results for patients with myeloma were not reported separately
- Phase I and II studies
- Letter and editorials
- Reports published in a language other than English