Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer.
OBJECTIVE
Despite substantial variability in individual risk of skeletal complications, patients with metastatic bone disease are treated with bisphosphonates at the same dose and dosing interval. This study assessed the feasibility of conducting a randomized trial of less frequent bisphosphonate administration in women with breast cancer and low-risk bone metastases.


METHODS
A randomized feasibility study was conducted. Patients receiving intravenous bisphosphonates for ≥3 months and with low-risk baseline serum C-telopeptide (CTx) levels (<600 ng/L) were assigned to pamidronate 90 mg intravenously every 3 to 4 weeks (control) or every 12 weeks (de-escalated). CTx, bone alkaline phosphatase, and pain scores (Brief Pain Inventory and Functional Assessment of Cancer Therapy-Bone Pain) were collected every 12 weeks for 48 weeks.


RESULTS
Fifty-four patients were approached, 44 consented, and 38 were randomized. Median age was 55 (range, 29 to 77) and median baseline CTx was 163 ng/L (range, 10 to 526). Fourteen control group participants (73.7%) and 13 de-escalated group participants (68.4%) maintained CTx in the low-risk range (P=0.64). All patients changing to higher-risk range had progressive extraskeletal disease. Compared with the control group, there was a time-dependent increase in CTx in the de-escalated group. There were no significant differences in bone alkaline phosphatase, Brief Pain Inventory, or Functional Assessment of Cancer Therapy-Bone Pain.


CONCLUSIONS
It is feasible to conduct randomized trials of de-escalated pamidronate in low-risk women treated with ≥3 months of prior bisphosphonate therapy. De-escalated scheduling satisfied our predefined definition of noninferiority compared with 3- to 4-weekly treatment. Larger trials should assess whether increasing CTx levels with de-escalated therapy lead to higher rates of skeletal complications.
*Division of Medical Oncology and Hematology, University of Toronto and Princess Margaret Hospital ‡Ambulatory Care, Princess Margaret Hospital §Toronto General Research Institute, University of Toronto and University Health Network ∥Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto †Department of Medical Oncology, R.S. McLaughlin Durham Regional Cancer Centre, Oshawa ¶Division of Medical Oncology, University of Ottawa and The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.
Eitan
E
Amir
Orit
O
Freedman
Lindsay
L
Carlsson
George
G
Dranitsaris
George
G
Tomlinson
Andreas
A
Laupacis
Ian F
IF
Tannock
Mark
M
Clemons
D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010147:Pain Measurement; D000077268:Pamidronate; D011379:Prognosis
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate