Effect of zoledronate on persisting isolated tumor cells (ITC) in the bone marrow (BM) of patients without recurrence of early breast cancer

Rack, Brigitte; Janni, W; Schoberth, A.; Scheffold, Christian; Strobl, B.; Blankenstein, Thomas; Rjosk, D.; Heinrigs, M.; Sommer, H.; Friese, Klaus

doi:10.1200/jco.2004.22.90140.9515

Cited by 47 publications

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“…50 In 4 small trials in patients with BC, adjuvant ZOL reduced the numbers of disseminated tumor cells (DTCs) in the bone marrow compared with baseline. [51][52][53][54][55] Patients with early BC and DTCs in the bone marrow (N ¼ 45) who received endocrine therapy plus ZOL (4 mg per month iv for up to 2 years) had significant decreases in bone marrow DTCs at the 1-year follow-up (P ¼ .0006) and the 2-year followup (P ¼ .0026) compared with baseline. 52 In a subsequent randomized study among patients with early BC and DTCs in the bone marrow (N ¼ 96), adding ZOL (4 mg per month iv for up to 2 years) to adjuvant therapy resulted in a higher proportion of patients with negative bone marrow assessments compared with patients who received endocrine therapy alone (66.7% vs 35.1%, respectively; P ¼ .009).…”

Section: Indirect Anticancer Effectsmentioning

confidence: 98%

“…54 In a larger, matched-pair study (N ¼ 172) among patients with DTCs in bone marrow, patients who received adjuvant chemotherapy plus ZOL (4 mg per month iv) for 6 months were more likely to be free of DTCs at subsequent assessment compared with patients who received chemotherapy alone (P ¼ .099 for between-group comparison). 53 However, the science of DTC research still is evolving, and it is unclear whether DTC numbers or specific types of DTCs (which may have different sensitivities to therapy) are important for disease recurrence. Nonetheless, the results from these studies suggest that ZOL may indirectly prolong survival by reducing the viability or proliferation of the DTCs within the bone marrow that could be the source for disease recurrence.…”

Section: Indirect Anticancer Effectsmentioning

confidence: 99%

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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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Section: Indirect Anticancer Effectsmentioning

confidence: 98%

Section: Indirect Anticancer Effectsmentioning

confidence: 99%

Zoledronic acid use in cancer patients

Coleman

Cook

Hirsh

et al. 2010

Cancer

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“…2,3,[13][14][15][16][17] Recently, preclinical and clinical data have also demonstrated anticancer effects of bisphosphonates in breast and other cancer types. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The prevention and treatment of bone loss with upfront (initiated simultaneously with letrozole) versus delayed (initiated with a decrease in T score to <À2 or occurrence of clinical nontraumatic fracture) zoledronic acid in early breast cancer patients receiving letrozole was evaluated in 3 similarly designed, geographically diverse studies (Z-FAST; ZO-FAST; E-ZO-FAST) and in the similarly-designed N03CC study. 15 Interim (<36 months follow-up) results from the former 3 studies indicate that upfront rather than delayed-start zoledronic acid is significantly more effective in preventing bone loss.…”

Section: Introductionmentioning

confidence: 99%

Final 5‐year results of Z‐FAST trial

Brufsky

Harker

Beck

et al. 2011

Cancer

164

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BACKGROUND: Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting. METHODS: Overall, 602 postmenopausal women with early, hormone receptor-positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence. RESULTS: At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9% and 6.7%, respectively (P < .0001, for both). Approximately 25% of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3%]; delayed, 33 [11%]; P ¼ .3803) and KaplanMeier disease recurrence rates (upfront, 9.8 [95% confidence interval (CI), 6.0-10.3]; delayed, 10.5 [95% CI, 6.6-14.4]; P ¼ .6283) were similar at month 61. CONCLUSIONS: Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long-term coadministration of letrozole and zoledronic acid is well tolerated.

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“…In small studies, ZOL (4 mg/month) increased the proportion of DTC-free patients who remained DTC-free at 6 months versus no ZOL [36], and significantly decreased DTC levels versus baseline at 12 (P < 0.0006) and 24 months (P = 0.0026) [37] in DTC-positive BC patients. Therefore, it is reasonable to hypothesize that ZOL may delay disease recurrence.…”

Section: Clinical Relevance Of Bisphosphonate Treatment In Adjuvant Smentioning

confidence: 99%

Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

Banys¹,

Solomayer²,

Gebauer³

et al. 2013

Senologie - Zeitschrift für Mammadiagnostik und -therapie

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Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068).

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Effect of zoledronate on persisting isolated tumor cells (ITC) in the bone marrow (BM) of patients without recurrence of early breast cancer

Cited by 47 publications

References 0 publications

Zoledronic acid use in cancer patients

Zoledronic acid use in cancer patients

Final 5‐year results of Z‐FAST trial

Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

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