Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

Berenson, James R.; Lichtenstein, Alan; Porter, Lester; Dimopoulos, Meletios A.; Bordoni, Roldolfo; George, Sebastian; Lipton, A.; Keller, Alan; Ballester, Oscar F.; Kovacs, Michael J.; Blacklock, Hillary; Bell, Richard H.; Simeone, Joseph F.; Reitsma, Dirk J.; Heffernan, Maika; Seaman, John J.; Knight, Robert D.

doi:10.1200/jco.1998.16.2.593

Cited by 575 publications

(347 citation statements)

References 24 publications

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“…Despite antiresorptive therapy, repair of existing lesions is not seen, and progressive disease is associated with new skeletal events. (8)(9)(10)(11)(12)(13) New strategies to reduce skeletal-related events and improve patient outcome are urgently required.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

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Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis ( p < .01), promotes bone formation ( p < .01) and increases bone mass in vivo ( p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption ( p < .05) and suppression of bone formation ( p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis ( p < .01), prevents myeloma-induced suppression of bone formation ( p < .05), blocks the development of osteolytic bone lesions ( p < .05), and increases survival ( p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction ( p < .001) and inhibits bone metastases ( p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. ß

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Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

View full text Add to dashboard Cite

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“…8 Clinical studies have suggested that BPs may induce a reduction of the tumor burden 9 and may prolong the survival of MM patients. 10,11 We have evaluated if the combination of zoledronate (Zln), a potent antiresorptive BP, 12 and dexamethasone (Dex), which is commonly used in the treatment of MM, could strengthen the inhibition of cell growth and the induction of apoptosis in human myeloma cell lines in vitro. Here, we show that the combination of both agents results in synergistic anti-myeloma effects, providing a rationale for in vivo investigations on this therapeutical combination.…”

Section: Introductionmentioning

confidence: 99%

Growth inhibition and synergistic induction of apoptosis by zoledronate and dexamethasone in human myeloma cell lines

et al. 2000

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Bisphosphonates (BPs) are commonly used in the treatment of myeloma-associated osteolytic lesions. Recent reports have suggested that BPs may also exert direct antitumor effects on myeloma cells. Here, we show that the treatment of myeloma cell lines with the combination of the potent BP zoledronate and dexamethasone inhibits cell growth and synergistically induces apoptotic cell death, providing a rationale for potential applications in vivo. Leukemia (2000) 14, 841-844.

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“…Patients receiving pamidronate had a significant reduction in both the proportion who experienced skeletal events (pathologic fractures, need for operation to treat or prevent pathologic fractures, need for radiation to bone or spinal cord compression) and the number of skeletal lesions per year. The pamidronate group also had a decreased requirement for analgesic drugs and had an improved quality of life (45). Bisphosphonates may induce apoptosis in humanmyelomacell cultures and thus exert a direct effect on multiple myeloma.…”

Section: Managementof Complicationsmentioning

confidence: 99%

Current Therapy of Multiple Myeloma.

Kyle

2002

Intern. Med.

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Not all patients who fulfill the minimal criteria for the diagnosis of multiple myelomashould be treated. If a patient is younger than 70 years, autologous peripheral blood stem cell transplantation should be seriously considered. Major challenges for stem cell transplantation are: 1) the inability to eradicate multiple myelomafrom the patient, and 2) removal of myelomacells and their precursors from the rein fused stem cells. Allogeneic transplantation cannot be recommendedat present because of the excessive mortality. Nonmyeloablativeapproaches are promising. There is no evidence that combinations of alkylating agents are superior to melphalan and prednisone. The use of thalidomide and intermittently administered prednisone for maintenance is being explored. Newagents include the immunomodulatory drugs, inhibitors of the ubiquitin proteasone pathway such as PS-341, antiangiogenesis drugs including 2-methoxy-estradiol, and farnesyl transferase inhibitors. Management of skeletal complications, hypercalcemia, anemia, infection, spinal cord compression, and renal insufficiency is discussed. (Internal Medicine 41: 175-180, 2002)

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Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.

Abstract: Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.

Cited by 575 publications

References 24 publications

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Growth inhibition and synergistic induction of apoptosis by zoledronate and dexamethasone in human myeloma cell lines

Current Therapy of Multiple Myeloma.

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