Effect of metronomic use of zoledronic acid (ZOL) on antitumor and antiosteoclastic effects in breast cancer patients with bone metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14603-e14603
Author(s):  
H. Xi-Chun ◽  
X. Zhao ◽  
X. Xu ◽  
H. Guo ◽  
Z. Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Dose ◽  
Zoledronic Acid ◽  
Cancer Patients ◽  
Low Dose ◽  
Randomized Study ◽  
Serum Levels ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Antitumor Effects

e14603 Background: Zoledronic acid (ZOL) can reduce the risk of skeletal-related events (SREs) and may have direct and indirect antitumor effects, which have been shown in animal models, pilot clinical studies as well as in recent phase III randomized trials. However, the pharmacokinetics of the drug in breast cancer patients remains to be elucidated and optimized. The purpose of this randomized study was to compare the effects of ZOL on osteoclasts and angiogenesis between a weekly low-dose versus a conventional dosage. Methods: Sixty breast cancer patients with bone metastases were recruited in this randomized phase II clinical study. The participants either received ZOL 1mg IV weekly for 4 doses or a single dose of ZOL 4mg IV. No other antitumor treatments were administered. During the first month after initial infusion of ZOL, serial blood samples were collected on day 1, 15 and 29 measuring markers for bone resorption (NTx), angiogenesis (VEGF), and tumor burden (CEA and CA15–3). Results: Compared to a single-dose administration, weekly low dose of ZOL resulted in a greater reduction in serum levels of VEGF and NTx, with a significant trend over time during one month observation. There were no statistically significant differences in circulating levels of CEA and CA15–3 between the two dosing regimens. Patients who received metronomic ZOL had a longer median time to disease progression (TTP) (7.0 months, 95%CI, 6.1–7.9 months) than those who had a single dose of ZOL (2.8 months, 95%CI, 0–5.7 months; p=0.076). Conclusions: The metronomic use of low-dose ZOL 1 mg appeared to be more effective than the conventional regimen in the long-lasting reduction of VEGF and NTx, and in prolonging TTP. This dosing schedule should be further assessed in phase III trials as we demonstrated that ZOL 1mg has greater antitumor properties in our study. No significant financial relationships to disclose.

Randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1141-TPS1141
Author(s):  
Norio Kohno ◽  
Yoshie Hasegawa ◽  
Jun Horiguchi ◽  
Takashi Ishikawa ◽  
Daishu Miura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Zoledronic Acid ◽  
Sample Size ◽  
Cancer Patients ◽  
Menopausal Status ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Antitumor Effects

TPS1141 Background: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate, and it induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. ZOL has also been found to have antitumor effects that include an angiogenesis inhibiting action, an inhibitory effect on tumor cell adhesion to and invasion of the extracellular matrix, and activation of a gdT cells. In addition, it has been found to have a synergistic apoptosis-inducing effect when used in combination with antitumor drugs. In this study we will investigate the pCR rate when ZOL is added to anthracycline followed by taxane to treat T2 and T3 breast cancer patients. Methods: Women with resectable invasive StageIIA-IIIB (T ≥ a3 cm or T ≥ a2 cm and lymph node positive) breast cancer who are HER-2-negative, between 20 and 70 years of age, and ECOG PS 0-1 are eligible. Patients with distant metastasis, patients who have had received chemotherapy, hormone therapy, or radiotherapy for breast cancer, patients with serious complications, such as heart disease or an infection, patients with a complicating dental or jaw infection or traumatic condition of the teeth, and patients with a history of treatment with a bisphosphonate within the previous 12 months are excluded. A total of 4 courses of FEC100 are administered every 3 weeks followed by weekly paclitaxel for 12 courses. ZOL 4mg is administered every 3-4 weeks a total of 7 times. Patients are randomized 1:1 to chemotherapy + ZOL group or chemotherapy alone group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and their menopausal status. The primary endpoint is pCR. Secondary endpoints are tumor response rate, the breast-conserving surgery ratio, and disease-free survival (DFS). We calculated the sample size on the basis of a pCR rate of 18% in the chemotherapy alone group and 35% in the chemotherapy + ZOL group, at a one-sided significance rate of 5%, and test power of 80%, and as a result we will target a patient sample size of 180 patients. 162 of planned 180 patients have been enrolled as of January 24, 2012.

scholarly journals Retrospective analysis of antitumor effects of zoledronic acid in breast cancer patients with bone-only metastases

Cancer ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2039-2047 ◽  
Author(s):  
Naoki Niikura ◽  
Jun Liu ◽  
Naoki Hayashi ◽  
Shana L. Palla ◽  
Yutaka Tokuda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Retrospective Analysis ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Antitumor Effects

Gruppo Oncologico Nord Ovest – Mammella Intergruppo (GONO MIG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 212-222
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Randomized Study ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Positive ◽  
Positive Breast Cancer

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Gruppo Oncologico Nord Ovest – Mammella Intergruppo (GONO MIG). Clinical trials include: Standard CEF versus accelerated CEF as adjuvant chemotherapy in node-positive or high-risk node-negative (T > 2 cm, age <35 years, G3, negative hormone receptors or high TL1 or S-phase) breast cancer. A phase III randomized trial. MIG-1Epirubicin plus paclitaxel versus cyclophosphamide, epirubicin and 5-fluorouracil as adjuvant chemotherapy in node-positive breast cancer patients. A phase III randomized study. MIG-5A phase III randomized study of sequential epidoxorubicin plus cyclophosp-amide followed by docetaxel (EC D) versus a combination of 5-fluorouracil, epidoxorubicin and cyclophosp-amide (FEC) as adjuvant treatment of node-negative early breast cancer patients.A phase III randomized study of EC followed by paclitaxel versus FEC followed by paclitaxel, all given either every 3 or 2 weeks supported by pegfilgrastim, for node-positive breast cancer patients.Prevention of chemotherapy-induced menopause by temporary ovarian suppression with triptorelin versus control in young breast cancer patients. A randomized phase III multicenter study.Letrozole adjuvant therapy duration (lead) study: standard versus long treatment. A phase III trial in post-menopausal women with early breast cancer.

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