NCCN guidelines for adjuvant therapy of breast cancer with bone metastases 2015v3

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Supportive Therapy for Bone MetastasesAdjuvant therapy of bone metastasesTreatment targeting osteoclast activity is of value in patients wit


Supportive Therapy for Bone Metastases

Adjuvant therapy of bone metastases

Treatment targeting osteoclast activity is of value in patients with metastatic breast cancer in bone to prevent bone fractures, bone pain requiring radiation therapy, spinal cord compression, and hypercalcemia (skeletal-related events; SREs).

Targeted therapy of osteoclast activity in breast cancer patients with bone metastasis is the value of fracture prevention, need radiotherapy for bone pain, spinal cord compression and hypercalcemia (bone related events; SRES)

The bisphosphonates zoledronic acid or pamidronate have been used for this purpose, and there is extensive clinical trial support for their efficacy in prevention of SREs (see section below on Bisphosphonates).

Bisphosphonate zoledronic acid or pamidronate two sodium has been used for this purpose, the preventive effect of SREs support extensive clinical trials (see Chapter bisphosphates).

Denosumab is a human antibody against RANK ligand, a mediator of osteoclast function. directed fully monoclonal

Denosumab is a fully human monoclonal antibody against a mediated osteoclast function RANK ligand.

A single, randomized, active, controlled trial metastatic cancer showed and of time to occurrence of SRE with denosumab, as compared with zoledronic acid. the equivalency breast superiority

Metastatic breast cancer: a single center, randomized controlled study showed effectiveness, compared to zoledronic acid and equivalent denosumab to SRE time better.

No study of or has demonstrated impact on OS in patients with metastatic disease. an denosumab bisphosphonate

No studies showing effects of bisphosphonates or denosumab for patients with metastatic disease OS.

The bisphosphonates and are with a of of osteonecrosis of the jaw (risk) (ONJ) in associated denosumab

Osteonecrosis of the jaw of bisphosphonates and denosumab (ONJ) and the occurrence of risk.

Poor baseline dental or procedures during are known risk factors for health treatment dental ONJ.

Dental health is known to be a risk factor for ONJ during baseline dental health or during treatment.

Thus, a dental examination with preventive dentistry intervention is recommended prior to treatment with intravenous bisphosphonate or denosumab, and dental procedures during treatment should be avoided if at all possible.

Therefore, the recommended oral dental examination before intravenous bisphosphonate therapy or denosumab prevention intervention, during treatment should be avoided as much as possible dental surgery.

Additional risk factors the of ONJ administration chemotherapy or corticosteroids and poor oral hygiene with periodontal disease and of dental abscess. for include development

Additional risk factors for ONJ include chemotherapy or hormonal and poor oral hygiene practices associated with periodontal disease, dental abscess.

Confirmation of metastatic disease by imaging, including X-ray, diagnostic CT, or MRI, and initial evaluation of serum calcium, creatinine, phosphorous, and magnesium levels should be undertaken prior to the initiation of intravenous bisphosphonate treatment or subcutaneous denosumab treatment in patients with metastatic disease.

By X-ray, CT or MRI images confirm the diagnosis of metastatic disease, should detect the serum calcium, creatinine, phosphorus and magnesium levels before intravenous bisphosphonate or subcutaneous injection of denosumab therapy.

Frequent measurement of calcium, phosphorous, and magnesium be since hypophosphatemia and have hypocalcemia been reported. may prudent

Frequent determination of calcium, phosphorus and magnesium, because there have been reports of hypophosphatemia and hypocalcemia can occur.



An intravenous bisphosphonate (eg, pamidronate, zoledronic, acid) in combination with oral calcium citrate and vitamin D supplementation should be used in women with bone metastasis, especially if lytic and/or in weight-bearing bone, if expected survival is 3 months or longer, and if creatinine levels are below mg/dL 3 (Category 1).

Bone metastasis in women should use intravenous bisphosphonates (e.g. pamidronate sodium two, zoledronic acid) combined with oral calcium citrate and vitamin D, especially if osteolytic and / or weight-bearing bone, expected survival time more than 3 months, serum creatinine level was lower than that of 3mg/dL (1).

Bisphosphonates are in addition chemotherapy or endocrine given to therapy.

In addition to chemotherapy or endocrine therapy must be given bisphosphonates.

Zoledronic acid be superior pamidronate in lytic breast may to metastasis.

In breast osteolytic metastases may be superior to zoledronic acid pamidronate sodium two.

There are extensive from trials in of the of bisphosphonates for patients with metastatic disease support to bone. use randomized data

There are a lot of data from randomized controlled trials of bone support in patients with metastatic disease treated with bisphosphonates.

The randomized clinical data the use zoledronic and pamidronate in the United States and ibandronate and clodronate in acid European countries. trial of include

Data from randomized clinical trials in the United States including use of zoledronic acid and pamidronate sodium and two in European countries, ibandronate and clodronic acid sodium two.

In metastatic bone disease, bisphosphonate treatment associated fewer skeletal-related events, fewer pathologic fractures, and less need radiation therapy surgery to and treat bone pain. is for

In metastatic bone disease, bisphosphonate treatment of skeletal related events, less pain, less pathological fractures require less radiotherapy and surgery.

The use of in disease is a palliative care bisphosphonates metastatic measure.

The use of bisphosphonates in metastatic disease is a palliative care measure.

No impact on has observed in patients treated with OS been bisphosphonates.

In patients treated with bisphosphonate was not observed on the OS effect.

The data indicate zoledronic and pamidronate be on a to 5-week schedule conjunction with antineoplastic therapy (ie, endocrine therapy, chemotherapy, biologic, therapy) in, in May acid given

The data show that zoledronic acid and pamidronate sodium per week two 3-5 administered 1 times with anti-tumor therapy (i.e., endocrine therapy, chemotherapy and biological therapy).

Recent data from a phase III study showed zoledronic acid administered once every versus the current standard 12 weeks of once every four weeks does not compromise efficacy among women with breast cancer and bone metastases.

The new phase III study showed that zoledronic acid was administered 1 times per week in women with breast cancer who did not have a reduced efficacy compared with the current standard of 1 times every 4 weeks.

The SRE rate 22% when was every weeks versus 23.2% when administered once in 12 weeks. administered 4 was zoledronic

SRE zoledronic acid was administered 1 times every 4 weeks and was administered at a dose of 22% for each of the 12 weeks, at a rate of 23.2%.

The use of should accompanied calcium vitamin supplementation with daily doses calcium of 1200 to mg of 1500 and D3 vitamin 400 to 800 bisphosphonates IU. and be by

The use of bisphosphonates should be supplemented with calcium and vitamin D, a daily dose of calcium 1200-1500mg, vitamin D3 400-800 IU.

Recommended agents for in United are pamidronate 90 mg over 2 hours zoledronic acid or mg intravenously over 15 States of 4 minutes. (intravenously use)

In the United States recommended drug pamidronate sodium two 90 mg intravenous drip for 2 hours or zoledronic acid 4 mg intravenously over 15 minutes.

The original studies treatment up to 24 months; however, there are long-term data indicating treatment can continue beyond that for time. safety limited continued

The original study continues to be treated for up to 24 months; limited long-term safety data suggest that treatment can continue to exceed that time.

The risk of toxicity monitoring of creatinine to administration of each dose and dose reduction or discontinuation if renal necessitates function is reduced. prior serum renal

The risk of nephrotoxicity requires monitoring of serum creatinine prior to each administration.

Current clinical results support use bisphosphonates for up to 2 years. of the trial

Current clinical trials support the use of bisphosphonates up to two years.

Longer durations of therapy provide additional benefit, but this not yet tested in been clinical trials. bisphosphonate may has

Bisphosphonate therapy may provide additional benefit for longer duration, but has not been validated in clinical trials.

ONJ, a complication bisphosphonate treatment, has been described. of

ONJ, a complication of bisphosphonate therapy has been described.

In a review of more than 16000 cancer patients, an increased risk for jaw or facial bone surgery along with an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw with the use of intravenous bisphosphonates was documented.

In a review of more than 16000 cases of cancer patients, with the use of intravenous bisphosphonates, diagnosis of risk for jaw inflammation or osteomyelitis of the jaw or face risk and increase bone surgery.

An absolute risk 5.48 events per treated was seen patients, with increase in associated with an increase in cumulative risk dose of drug. an of

Each of the 100 treated patients saw an absolute risk of 5.48 events, with an increase in cumulative dose risk.

It is recommended patients undergo a examination with dentistry prior to initiation preventive of bisphosphonate therapy. dental should that

At the beginning of bisphosphonate therapy before the patients should receive preventive dental examination.



Therapy with metastatic cancer bone are candidates bisphosphonate may also be considered for treatment with denosumab (Category 1) in Women who to breast

Bone metastasis of breast cancer women for bisphosphonate therapy can be considered denosumab treatment (Class 1).

This recommendation is on results of single randomized trial comparing denosumab to zoledronic acid. a the based

This is a comparison of denosumab and zoledronic acid based on the results of independent random test.

All trial patients recommended supplement with vitamin D and were to calcium.

All patients were advised to supplement vitamin D and calcium.

Patients on the experimental arm were given of denosumab injected subcutaneously 120 mg every 4 weeks plus intravenous placebo versus the control arm where patients were given an intravenous infusion of mg of zoledronic acid 4 every 4 weeks, and a subcutaneous placebo.

The experimental group patients were given denosumab 120 mg subcutaneously every 4 weeks 1 times plus intravenous placebo and the control group were treated with zoledronic acid 4 mg every 4 weeks 1 times of intravenous and subcutaneous placebo.

In this trial with non-inferiority as the primary endpoint, denosumab was shown to significantly delay time to first SRE by as compared with zoledronic acid 18% (HR, 0.82; 95% CI, 0.71- 0.95; P <.001 for non-inferiority; P =.01 for superiority and to first and) time subsequent SREs (rate ratio, 0.77; 95% CI, 0.66-0.89; P =.001).

The main end point of this test is non inferiority, and zoledronic acid compared denosumab significantly delayed the first SRE18% (HR, 0.82; CI 0.71-0.95 95%; non inferiority P<.001; P =.01) and SREs to the first or second time (rate ratio, 0.77; 95% CI, 0.66-0.89; P=.001).

No difference time to or OS was in progression observed.

No differences were observed in progression time or OS.

Adverse event profiles similar the two groups, including incidence ONJ of, with a risk of and acute phase adverse events in the denosumab treatment were group. renal-related reduced

Similar adverse events of two groups, including the incidence of ONJ, denosumab treatment group and acute kidney related adverse event risk reduction.

Long-term risks denosumab treatment are of unknown.

The long-term risk of unknown denosumab treatment.

The optimal of treatment denosumab is not duration with known.

Denosumab treatment optimum duration is not clear.

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