Differential Effect of Doxorubicin and Zoledronic Acid on Intraosseous versus Extraosseous Breast Tumor Growth <i>In vivo</i>

Ottewell, Penelope D.; Deux, Blandine; Mönkkönen, Hannu; Cross, Simon S.; Coleman, Robert E.; Clézardin, Philippe; Holen, Ingunn

doi:10.1158/1078-0432.ccr-07-1545

Cited by 88 publications

(94 citation statements)

References 38 publications

(43 reference statements)

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“…This difference can to some extent be justified by the higher level of overall bone turnover in young mice, compared with adult humans. Treatment of established B02 breast tumors in bone with a single injection of 100 μg/kg zoledronic acid has been shown to have no effect on tumor volume, tumor cell apoptosis, or proliferation (23,32). However, an accumulative dose of 100 μg/kg, where mice were given zoledronic acid daily or weekly, significantly reduced intraosseous tumor burden (23).…”

Section: Discussionmentioning

confidence: 99%

“…1). The limited number of groups was based on our previous work showing that giving the two agents in combination only has an intermediary effect, and that the reverse sequence does not induce increased antitumor effects compared with the single agents (32,33). The doses used in this study are comparable with clinical doses of both compounds.…”

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

“…Osteoclast Histochemistry Osteoclasts were detected in sections of tumor-bearing tibiae by toluidine blue and tartate-resistant acid phosphatase staining as previously described (32). Two 5-μm sections per sample were scored; the numbers of osteoclasts per millimeter of cortical bone surface and the area of bone surface in contact with osteoclasts were quantified using a Leica RMRB upright microscope and OsteoMeasure software (Osteometrics) as previously described (32).…”

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

“…Two 5-μm sections per sample were scored; the numbers of osteoclasts per millimeter of cortical bone surface and the area of bone surface in contact with osteoclasts were quantified using a Leica RMRB upright microscope and OsteoMeasure software (Osteometrics) as previously described (32).…”

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

“…However, these studies used high doses of zoledronic acid ranging from a single injection of 250 to 100 μg/kg 2× per week. We have recently shown that administration of a clinically relevant dose of doxorubicin (2 mg/kg) followed by a single injection of zoledronic acid (100 μg/kg) reduces intraosseous tumor growth in the B02 model of breast cancer bone metastases (32). Optimal antitumor effects were observed when doxorubicin was administered 24 hours before zoledronic acid, whereas giving the two drugs at the same time had no effect on tumor growth, indicating that the sequence in which these agents are administered my be important to achieve maximal therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

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Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone

Ottewell

Woodward

Lefley

et al. 2009

Molecular Cancer Therapeutics

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Patients with advanced breast cancer frequently develop bone metastases, and at this stage, the disease is considered incurable. Here, we show that a 6-week course of weekly administration of doxorubicin (2 mg/kg), followed 24 hours later by the bisphosphonate zoledronic acid (100 μg/kg), causes substantial inhibition of MDA-MB-436 breast tumor burden in bone of immunocompromised mice, compared with administration of the single agents.

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Section: Discussionmentioning

confidence: 99%

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

Section: Inoculation Of Bone Tumors and Drug Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone

Ottewell

Woodward

Lefley

et al. 2009

Molecular Cancer Therapeutics

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An animal model for chemotherapy‐associated steatohepatitis and its prevention by the oral administration of fatty acid bile acid conjugate

Keizman

Maimon

Ish‐Shalom

et al. 2009

Cancer

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BACKGROUND: Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH). This increases the risk of perioperative morbidity and mortality. To the authors' knowledge, an animal model for CASH has not been described previously. It has been established that fatty acid bile acid conjugates (FABACs) prevent the formation of diet-induced fatty liver. The current study was designed to establish an animal model of CASH and to use that model to study the effect of FABACs on its occurrence. METHODS: C57BL/6 mice were given different doses of oxaliplatin and irinotecan. Oxaliplatin administered once weekly at a dose of 6 mg/kg for a total dose of 24 mg/kg was tolerated best and was associated most consistently with CASH. Thus, that dose was chosen as the induction model for CASH. Subsequently, mice were divided into a control group (no treatment), an oxaliplatin group, and a CASH-prevention group, which received oxaliplatin and C20-FABAC at a dose of 150 mg/kg daily. The animals were killed after 28 days. RESULTS: Liver fat content was significantly lower (P < .0001) in the control group (51.63 mg/g) and the prevention group (62.13 mg/g) compared with the oxaliplatin group (95.35 mg/g). This difference was mainly because of the accumulation of liver triglycerides in the oxaliplatin group. CONCLUSIONS: The current results indicated that C57BL/6 mice receiving weekly oxaliplatin can be used as a model for CASH. Oral FABAC therapy reduced the development of CASH in animals that received oxaliplatin. To the authors' knowledge, this report is the first description of a model and a potential preventive treatment for CASH. Cancer 2010;116:251-5.

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Zoledronic acid use in cancer patients

Coleman

Cook

Hirsh

et al. 2010

Cancer

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Bone is the most common site for metastasis from solid tumors, and the majority of patients will develop bone metastases during the natural course of their disease. Bisphosphonates are an effective treatment for preventing skeletal-related events in patients with bone metastases and may preserve functional independence and quality of life. Although several bisphosphonates have been investigated in patients with solid tumors, only zoledronic acid (ZOL) is approved by the US Food and Drug Administration and the European Medicines Agency for preventing skeletalrelated events in patients across a broad range of solid tumors. In addition, bisphosphonates, notably ZOL, prevent cancer treatment-induced bone loss in breast and prostate cancer patients who are receiving endocrine therapy. It also has been demonstrated that ZOL directly and indirectly inhibits cancer cell growth in vitro and growth and tumorigenesis in animal model systems. These properties may produce clinically meaningful benefits. In recent clinical studies in patients with cancer, ZOL improved overall and prolonged disease-free survival. Ongoing clinical trials in patients with solid tumors will provide further insight into the potential of ZOL to prevent distant metastases and improve survival. Cancer 2011;117:11-23. V C 2010 American Cancer Society.KEYWORDS: adjuvant setting, bisphosphonate, bone metastases, cancer, survival, zoledronic acid.During the progression of cancer, many patients will develop distant metastases, for which a common site is bone. 1For example, an estimated 75% of patients with advanced breast cancer (BC) or prostate cancer (PC), and 40% of patients with advanced lung cancer (LC) develop bone metastases.2,3 Without bone-targeted therapies, most patients with bone metastases will experience potentially debilitating skeletal-related events (SREs), such as pathologic fractures, spinal cord compression, the need for surgery or palliative radiotherapy to bone, or hypercalcemia of malignancy.1 These SREs can have debilitating consequences and reduce quality of life and survival. 4 Moreover, declines in performance status resulting from SREs could preclude the receipt of chemotherapy and radiotherapy by patients with some solid tumors. 5Bisphosphonates, which are inhibitors of osteoclast-mediated bone resorption, currently are the standard of care for preventing SREs in patients with bone metastases.6 Several bisphosphonates currently are approved by the US Food and Drug Administration and the European Medicines Agency for preventing SREs in patients with metastatic BC and multiple myeloma (MM). In addition, the nitrogen-containing bisphosphonate (N-BP) zoledronic acid (ZOL) has received widespread regulatory approval for patients with bone involvement from PC, LC, and the entire range of other solid tumors (OSTs). 6 In randomized phase 3 trials, ZOL (4 mg intravenously [iv] every 3 to 4 weeks [monthly]) demonstrated significant efficacy in delaying the onset and reducing the risk of SREs and in palliating bone pain, reducing analges...

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Differential Effect of Doxorubicin and Zoledronic Acid on Intraosseous versus Extraosseous Breast Tumor Growth In vivo

Cited by 88 publications

References 38 publications

Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone

Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone

An animal model for chemotherapy‐associated steatohepatitis and its prevention by the oral administration of fatty acid bile acid conjugate

Zoledronic acid use in cancer patients

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