PURPOSE: Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain. METHODS: Exploratory analyses were performed in patients with bone metastases from breast cancer or lung cancer/other solid tumors enrolled in two randomized trials comparing monthly zoledronic acid versus pamidronate (breast cancer) or placebo (lung cancer/other solid tumors). Analyses included proportion of patients with one or more skeletal-related events, time to first skeletal-related event, and skeletal morbidity rate in patients with and without baseline pain. RESULTS: Approximately 80 % of patients reported baseline pain. Similar to overall trial results, zoledronic acid reduced the skeletal morbidity rate in all groups. Although some subsets lacked statistical power, benefits were generally greater in patients without baseline pain. For example, in breast cancer, zoledronic acid increased the 25th quartile of time to first skeletal-related event versus pamidronate by 522 days in patients with no baseline pain (median not reached for either group), but by only 10 days in patients with baseline pain. Similar trends were observed in lung cancer. CONCLUSIONS: Benefits from zoledronic acid appeared to be greater if introduced before bone pain onset. Early diagnosis and treatment of bone metastases may delay onset of skeletal-related events.
RCT Entities:
PURPOSE:Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain. METHODS: Exploratory analyses were performed in patients with bone metastases from breast cancer or lung cancer/other solid tumors enrolled in two randomized trials comparing monthly zoledronic acid versus pamidronate (breast cancer) or placebo (lung cancer/other solid tumors). Analyses included proportion of patients with one or more skeletal-related events, time to first skeletal-related event, and skeletal morbidity rate in patients with and without baseline pain. RESULTS: Approximately 80 % of patients reported baseline pain. Similar to overall trial results, zoledronic acid reduced the skeletal morbidity rate in all groups. Although some subsets lacked statistical power, benefits were generally greater in patients without baseline pain. For example, in breast cancer, zoledronic acid increased the 25th quartile of time to first skeletal-related event versus pamidronate by 522 days in patients with no baseline pain (median not reached for either group), but by only 10 days in patients with baseline pain. Similar trends were observed in lung cancer. CONCLUSIONS: Benefits from zoledronic acid appeared to be greater if introduced before bone pain onset. Early diagnosis and treatment of bone metastases may delay onset of skeletal-related events.
Authors: Catherine H Van Poznak; Sarah Temin; Gary C Yee; Nora A Janjan; William E Barlow; J Sybil Biermann; Linda D Bosserman; Cindy Geoghegan; Bruce E Hillner; Richard L Theriault; Dan S Zuckerman; Jamie H Von Roenn Journal: J Clin Oncol Date: 2011-02-22 Impact factor: 44.544
Authors: Lee S Rosen; David Gordon; N Simon Tchekmedyian; Ronald Yanagihara; Vera Hirsh; Maciej Krzakowski; Marek Pawlicki; Paul De Souza; Ming Zheng; Gladys Urbanowitz; Dirk Reitsma; John Seaman Journal: Cancer Date: 2004-06-15 Impact factor: 6.860
Authors: Kevin P Weinfurt; Liana D Castel; Yun Li; Justin W Timbie; G Alastair Glendenning; Kevin A Schulman Journal: Med Care Date: 2004-02 Impact factor: 2.983
Authors: M A Dimopoulos; E Kastritis; C Bamia; I Melakopoulos; D Gika; M Roussou; M Migkou; E Eleftherakis-Papaiakovou; D Christoulas; E Terpos; A Bamias Journal: Ann Oncol Date: 2008-08-09 Impact factor: 32.976
Authors: M Aapro; P A Abrahamsson; J J Body; R E Coleman; R Colomer; L Costa; L Crinò; L Dirix; M Gnant; J Gralow; P Hadji; G N Hortobagyi; W Jonat; A Lipton; A Monnier; A H G Paterson; R Rizzoli; F Saad; B Thürlimann Journal: Ann Oncol Date: 2007-09-28 Impact factor: 32.976
Authors: C I Ripamonti; M Maniezzo; T Campa; E Fagnoni; C Brunelli; G Saibene; C Bareggi; L Ascani; E Cislaghi Journal: Ann Oncol Date: 2008-07-22 Impact factor: 32.976
Authors: J-J Body; I J Diel; M R Lichinitser; E D Kreuser; W Dornoff; V A Gorbunova; M Budde; B Bergström Journal: Ann Oncol Date: 2003-09 Impact factor: 32.976
Authors: Gareth J Morgan; J Anthony Child; Walter M Gregory; Alex J Szubert; Kim Cocks; Sue E Bell; Nuria Navarro-Coy; Mark T Drayson; Roger G Owen; Sylvia Feyler; A John Ashcroft; Fiona M Ross; Jennifer Byrne; Huw Roddie; Claudius Rudin; Gordon Cook; Graham H Jackson; Ping Wu; Faith E Davies Journal: Lancet Oncol Date: 2011-07-21 Impact factor: 41.316
Authors: Donald L Patrick; Charles S Cleeland; Roger von Moos; Lesley Fallowfield; Rachel Wei; Katarina Öhrling; Yi Qian Journal: Support Care Cancer Date: 2014-12-23 Impact factor: 3.603
Authors: Jean-Jacques Body; Roger von Moos; Alex Rider; Pamela Hallworth; Debajyoti Bhowmik; Francesca Gatta; Guy Hechmati; Yi Qian Journal: J Bone Oncol Date: 2018-12-18 Impact factor: 4.072
Authors: Roger von Moos; Jean-Jacques Body; Blair Egerdie; Alison Stopeck; Janet Brown; Lesley Fallowfield; Donald L Patrick; Charles Cleeland; Danail Damyanov; Felipe Salvador Palazzo; Gavin Marx; Ying Zhou; Ada Braun; Arun Balakumaran; Yi Qian Journal: Support Care Cancer Date: 2015-09-02 Impact factor: 3.603
Authors: Roger von Moos; Jean-Jacques Body; Alex Rider; Jonathan de Courcy; Debajyoti Bhowmik; Francesca Gatta; Guy Hechmati; Yi Qian Journal: J Bone Oncol Date: 2017-11-24 Impact factor: 4.072