The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases

Daley‐Yates, Peter T.; Dodwell, David; Pongchaidecha, Manat; Coleman, Rob; Howell, Anthony

doi:10.1007/bf02555856

Cited by 50 publications

(31 citation statements)

References 11 publications

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“…These data agree with most other in vitro studies showing maximal growth inhibitory effects of BPs at doses higher than what is persistently achievable in the serum of patients after treatment. In fact, it has been shown that infusion of Pamidronate, which is a less potent antiresorptive BP commonly used in palliative treatments, gives serum concentrations B10-fold lower (0.5 -8 mM) (Daley-Yates et al, 1991;Oiso et al, 1994;Berenson et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro

et al. 2003

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Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21 ras pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21 ras . We found that ZOL induces growth inhibition (IC 50 :10 -50 mM) and apoptotic death of PC cells. The proapoptotic effect was correlated to cleavage/ activation of caspase-9 and poly(ADP)-ribose polymerase, but not of caspase-3. Moreover, we studied the p21 ras signalling in cells exposed to ZOL and detected a reduction of p21 ras and Raf-1 content and functional downregulation of the terminal enzyme ERK/ MAPkinase and of the pKB/Akt survival pathway. Finally, we observed that ZOL induces significant cytoskeletal rearrangements. In conclusion, we demonstrated that ZOL induces growth inhibition and apoptosis on PC cells and interferes with growth and survival pathways downstream to p21 ras . These findings might be relevant for expanding application of BPs in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro

et al. 2003

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“…It is well recognised that the majority of an intravenous infusion of pamidronate is adsorbed onto the bone surface (Daley Yates et al, 1991) where it remains bound to hydroxyapatite for a very long time -probably years. Therefore, a single infusion can theoretically have a prolonged duration of action on the osteoclast, causing sustained inhibition of bone resorption.…”

Section: Disasssionmentioning

confidence: 99%

High-dose intravenous pamidronate for metastatic bone pain

Purohit

Anthony²,

Radstone³

et al. 1994

Br J Cancer

139

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“…The etidronate and the clodronate, the first agents employed in clinical practice, have been replaced by a second generation of bisphosphonates, the pamidronate and the alendronate, that introduce a greater anti-reabsorption activity in comparison to the previous generation [10, 11, 12, 13]. A third generation of bisphosphonates is now available with the introduction on the market of zoledronate, which is more powerful in both vitro and vivo models of bone re-absorption [14].…”

Section: Introductionmentioning

confidence: 99%

Safety of Long-Term Administration of Bisphosphonates in Elderly Cancer Patients

et al. 2004

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Background: To evaluate the effectiveness and tolerability of the long-term treatment bone metastases with pamidronate in older patients. Materials and Methods: Twenty-two ambulatory patients aged 70 or older were included in the study. The median age was 73 (range 70–77). Ten patients (46%) were affected by breast carcinoma, 7 (32%) by prostate carcinoma and 5 (22%) by multiple myeloma. Nine (40%) patients presented co-morbidity. All of the patients presented at least one metastatic lytic bone lesion measuring 1 cm or more in diameter; the median lesion number was 2 (range 1–4). Hormonal therapy or chemotherapy regimen, were allowed as clinically required. Patients were treated with a fixed dose of sodium pamidronate, 90 mg in 3 h infusion every 4 weeks. Results: Partial response was shown in 6 (28%) patients, stable disease in 11 (50%), and progression (PD) in 5 (22%). 2 out of 5 patients with PD presented skeletal-related events (SREs) such as bone fracture. The median treatment duration was 19 months. The treatment was well tolerated; in 5 patients (23%) a GI fever was observed, in 3 patients (18%) G1 nausea, and in 3 patients (14) G1 diarrhea. Two cases (9%) of acute renal insufficiency (creatinine 1.7 and 1.6 mg/dl), and 3 cases (14%) of hypocalcemia (7.6, 7.5 and 7.8 mg/dl) were also registered. The renal dysfunction was reversible and without consequence. Conclusion: Our experience suggests that the bisphosphonates long-term administration is useful and did not cause significant side effects in elderly subjects. Low-grade pyrexia, nausea/vomiting, acute/reversible renal dysfunction and hypo-calcemia were the most frequent side effects reported. However, they were of low grade and in most cases, did not require dose modifications and/or hospitalization.

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The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases

Cited by 50 publications

References 11 publications

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro

High-dose intravenous pamidronate for metastatic bone pain

Safety of Long-Term Administration of Bisphosphonates in Elderly Cancer Patients

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