RESUMO
PURPOSE: Zoledronic acid (ZOL) given every 3 to 4 weeks can reduce skeletal-related events (SRE) in patients with bone lesions from multiple myeloma. This study evaluated efficacy and safety of less-frequent ZOL dosing based on bone turnover markers in patients with 1 to 2 years of prior bisphosphonate therapy. EXPERIMENTAL DESIGN: Patients received ZOL (4 mg) every 4 or 12 weeks based on urinary N-telopeptide of type 1 collagen (uNTX) levels (every 4 weeks if uNTX ≥50 nmol/mmol creatinine, every 12 weeks if uNTX < 50). RESULTS: Of 121 patients enrolled (mean age, 63.8 years; median follow-up, 21 months), 4 patients started ZOL every 4 weeks and 117 received ZOL every 12 weeks based on uNTX at study entry. All 4 patients who initiated ZOL every 4 weeks switched to every 12 weeks due to decreased uNTX. Thirty-eight of 117 patients who initiated ZOL every 12 weeks switched to ZOL every 4 weeks due to disease progression (n = 20), increased uNTX (n = 14), and SREs (n = 4). Overall SRE incidence was low; 7 (5.8%) and 5 (4.9%) patients experienced an SRE during years 1 and 2, respectively. Mean (SD) SRE rate at year 2 was 0.01 (0.03) per person-year. The 2-year incidence rate for osteonecrosis of jaw was 3.3%. Four deaths were reported, none related to ZOL. CONCLUSIONS: Less frequent ZOL dosing (every 12 weeks over 2 years) maintains a low SRE rate and can be safely administered for up to 4 years.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Doenças Ósseas/etiologia , Doenças Ósseas/metabolismo , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Mieloma Múltiplo/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas/patologia , Doenças Ósseas/prevenção & controle , Colágeno Tipo I/urina , Difosfonatos/efeitos adversos , Feminino , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estadiamento de Neoplasias , Osteólise/etiologia , Osteólise/metabolismo , Osteólise/patologia , Osteólise/prevenção & controle , Peptídeos/urina , Ácido ZoledrônicoRESUMO
An open-label study conducted in community centers assessed the safety of zoledronic acid 4 mg intravenously over 15 minutes every 3-4 weeks as treatment of bone metastases in patients with multiple myeloma, breast cancer, or prostate cancer with and without previous bisphosphonate exposure. Adverse events (AEs), pain, and quality-of-life (QOL) scores were recorded, and serum creatinine (SCr) levels were measured before each infusion. Of 638 patients, 415 patients (65%) had received prior bisphosphonate therapy. Fatigue, nausea, and arthralgia were the most frequent AEs. Nausea was more common in bisphosphonate-naive patients. SCr levels increased notably in 6.6% of patients: 7.7% of patients who received prior bisphosphonate therapy and 4.5% of bisphosphonate-naive patients. Treatment was delayed because of SCr-level increases in 1.4% of patients with prior bisphosphonate exposure and 0.4% of bisphosphonate-naive patients. SCr-level increases and treatment delays did not correlate with duration of prior bisphosphonate therapy. There was a trend towards more treatment discontinuations in patients with prior bisphosphonate exposure compared with bisphosphonate-naive patients. Pain scores decreased from baseline; total QOL scores remained constant. The results of this study suggest that, with proper SCr-level monitoring, cancer patients with bone metastases who have previously received intravenous bisphosphonate treatment can be safely converted to zoledronic acid therapy.