von Au Alexandra, Milloth Eva, Diel Ingo, Stefanovic Stefan, Hennigs Andre, Wallwiener Markus, Heil Joerg, Golatta Michael, Rom Joachim, Sohn Christof, Schneeweiss Andreas, Schuetz Florian, Domschke Christoph
Breast Unit, Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg.
CGG Clinic - Centrum für ganzheitliche Gynäkologie Mannheim, Mannheim, Germany.
Onco Targets Ther. 2016 Jul 8;9:4173-80. doi: 10.2147/OTT.S103130. eCollection 2016.
Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness.
In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter.
Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts.
We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.
转移性乳腺癌患者常因转移性骨病而感到不适。因此，骨保护是乳腺癌骨转移治疗的重要组成部分，双膦酸盐（BPs）是主要的治疗选择。在本研究中，我们的目标是比较口服与静脉注射BP治疗的副作用，并评估其临床疗效。
在这项前瞻性随机、开放标签、非劣效性试验中，我们纳入了至少有一处骨转移且东部肿瘤协作组体能状态为0 - 2的乳腺癌患者。患者被随机分配到三个治疗组之一：A组，静脉注射帕米膦酸60 mg，每3周一次；B - iv组，静脉注射氯膦酸900 mg，每3周一次；B - o组，每日口服氯膦酸2400 mg。在基线时以及此后每3个月进行评估。
1995年至1999年，321例确诊为乳腺癌骨转移的患者纳入研究。在首次随访时，胃肠道（GI）副作用最为常见，口服治疗组对胃肠道的不良反应更频繁（分别为P = 0.002和P < 0.001）。对于其他记录的副作用（皮肤、血清电解质、泌尿系统、免疫系统等），各治疗组之间无统计学显著差异。通过疼痛评分评估，各治疗组在BP治疗的临床疗效方面未检测到显著差异；然而，静脉注射BP比口服BP更有效地预防了病理性骨折（P = 0.03）。各研究组的不依从率相似。
我们得出结论，口服BP治疗与较高的胃肠道不良副作用发生率显著相关。此外，我们的数据表明，静脉注射BP在预防病理性骨折方面比口服治疗更有效；因此，应谨慎考虑口服给药。
