Supportive Care: More Than Just Treating Cancer

December 13, 2007

Strides made in the treatment of metastatic breast cancer (MBC) appear to prolong survival in some settings, but the cost in terms of quality of life (QOL) remains a concern. The previous four E-Updates in this series on metastatic breast cancer have focused on the various treatment options, including chemotherapy, anti-HER2 targeted therapy, antiangiogenic therapy, and hormonal therapy. In this E-Update, we turn to the role of supportive measures in the treatment of cancer, specifically as these measures relate to quality of life. These measures include the use of erythropoiesis-stimulating agents (ESA) and bisphosphonates, management of fatigue and pain, and psychological care.


Continuing Medical EducationSupportive Care: More Than Just Treating Cancer


Activity Release Date: December 13, 2007
Activity Expiration Date: December 13, 2008


About the Activity
This activity is based on a brief article developed as part of the E-Update Series and posted on the Web. It was developed from an identified educational need for information about practical management issues in the practice of medical, surgical, and radiation oncology. This activity has been developed and approved under the direction of Beam Institute.

Activity Learning Objectives
After reading this article, participants should be able to:

Understand the important role of supportive care in improving quality of life for patients with metastatic breast cancer.Identify the three erythropoiesis-stimulating agents used to treat chemotherapy-induced anemia and know when and how to use these agents.Identify the two bisphosphonates approved for use in the United States and know when and how to use them.Recognize the causes of cancer-related fatigue and be prepared to offer appropriate treatments.List the options available for managing pain associated with metastatic breast cancer and its treatment.Know the indications for adjuvant analgesics available as first-line treatment for nonmalignant pain and second-line treatment when opioid therapy has been optimized.Understand the complexity of cancer care, including physical symptoms, psychological stress, and social interactions with family, friends, and the work environment.Recognize that palliative care may be the most emotionally difficult phase of cancer treatment not only for patients and families, but also for clinical staff.

Target Audience
This activity targets physicians in the fields of oncology and hematology.



This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Beam Institute and The Oncology Group. Beam Institute is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation
The Beam Institute designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Compliance Statement
This activity is an independent educational activity under the direction of Beam Institute. The activity was planned and implemented in accordance with the Essential Areas and policies of the ACCME, the Ethical Opinions/Guidelines of the AMA, the FDA, the OIG, and the PhRMA Code on Interactions with Healthcare Professionals, thus assuring the highest degree of independence, fair balance, scientific rigor, and objectivity.

However, Beam Institute, the Grantor, and CMPMedica shall in no way be liable for the currency of information or for any errors, omissions, or inaccuracies in the activity. Discussions concerning drugs, dosages, and procedures may reflect the clinical experience of the author(s) or may be derived from the professional literature or other sources and may suggest uses that are investigational in nature and not approved labeling or indications. Activity participants are encouraged to refer to primary references or full prescribing information resources.

The opinions and recommendations presented herein are those of the author(s) and do not necessarily reflect the views of the provider or producer.

Financial Disclosures

Dr. Dang is a consultant and a member of the speakers' bureau and has received research support from Genentech. Dr. Hudis is a member of the speakers' bureau for AstraZeneca and Genentech and a member of the advisory boards of Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Sanofi-Aventis and Roche. Dr. Hudis has indicated ownership stock in Genomic Health. He has performed research for Kosan Biosciences.


Copyrights owned by Beam Institute, a division CME LLC. Copyright 2007. All rights reserved.

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Strides made in the treatment of metastatic breast cancer (MBC) appear to prolong survival in some settings, but the cost in terms of quality of life (QOL) remains a concern. The previous four E-Updates in this series on metastatic breast cancer have focused on the various treatment options, including chemotherapy, anti-HER2 targeted therapy, antiangiogenic therapy, and hormonal therapy. In this E-Update, we turn to the role of supportive measures in the treatment of cancer, specifically as these measures relate to quality of life. These measures include the use of erythropoiesis-stimulating agents (ESA) and bisphosphonates, management of fatigue and pain, and psychological care.


Clinical opinions expressed in this program are those of the authors and do not necessarily reflect the opinions of the supporters, publishers, editors, or officers of CMPMedica or Beam Institute.

Erythropoiesis-Stimulating Agents

Anemia is common in patients with cancer and is usually due to the disease itself or to the anticancer therapy. Anemia has a substantially negative impact on patients’ quality of life (QOL), inducing fatigue, reducing exercise tolerance, and possibly necessitating a reduction in the treatment dose or delay in the cycling of treatment.1,2

Before recombinant human erythropoietin became available in 1993, red blood cell (RBC) transfusion was the only standard option for the treatment of most anemia. Currently, three erythropoiesis-stimulating agents (ESAs) are used for the treatment of chemotherapy-induced anemia:


  • epoetin alfa (Epogen, Procrit, Eprex/Epypo);

  • epoetin beta (NeoRecormon), not marketed in the United States; and

  • the longer acting darbepoetin alfa (Aranesp)

The American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) first published evidence-based practice guidelines on the use of these agents in 20023 and the update committee revised the guidelines in 2007.4 Based on a comprehensive review comparing outcomes of patients with chemotherapy-induced anemia taking either epoetin or darbepoetin, the update committee found that these agents are equivalent in efficacy and safety at the approved doses recommended by the US Drug and Food Administration (FDA).4 In addition, in 2006, the BlueCross and BlueShield Association Technology Evaluation Center, under the Agency for Healthcare Research and Quality (AHRQ), conducted a Comparative Effectiveness Review (CER) of the use of epoetin or darbepoetin for managing anemia in patients being treated for cancer.5 The CER found that epoetin and darbepoetin were equivalent in terms of hematologic response rates, transfusion rates, and thromboembolic risks.


When to Initiate ESA for Chemotherapy-Induced Anemia


Hemoglobin Concentration Approaching or < 10 g/dL
The ASCO/ASH 2007 guidelines recommend that epoetin (alpha or beta) or darbepoetin may be used in patients with chemotherapy-induced anemia and hemoglobin (Hgb) approaching or < 10 g/dL.4 RBC transfusion is also an option.


A meta-analysis by Seidenfeld et al of controlled clinical trials using epoetin found that the strongest evidence that epoetin decreases the need for RBC transfusions and improves QOL outcomes came from trials in patients with Hgb of 10 g/dL or less.6 This meta-analysis also found insufficient data that using epoetin therapy at Hgb > 10 g/dL resulted in fewer RBC transfusions or improved QOL than did starting at Hgb ≤ 10 g/dL.


The AHRQ CER identified three important studies that compared the effects of immediate vs delayed ESA treatment on transfusion rates, thromboembolic events, QOL, and survival. In each of these trials, patients were randomized to the “immediate” or “delayed” arm and ESA was given when Hgb fell to a prespecified level. In all three trials, transfusion rates were higher in the delayed arms, but the differences were not statistically significant.7-9


Straus et al8 reported a higher thromboembolic rate in the immediate arm (11%) than in the delayed arm (3%), but no differences in clot risks were seen in the other two studies by Crawford et al7 or Reardon et al.9 Straus et al also found an improved QOL in the immediate arm as measured by the physical and functional well-being subscales of the Functional Assessment of Cancer Therapy-General (FACT-G), the anemia scale (FACT-An), and the fatigue subscale of the FACT-An.8 The other two studies, however, saw no differences in QOL between the immediate and delayed treatment arms.7,9

The AHRQ CER advises that the data on QOL improvement with ESAs are inconsistent and should be interpreted with caution.5 QOL is more difficult to measure than Hgb levels or transfusion changes. Furthermore, many older studies did not report QOL data. To date, it is not clear if ESAs significantly improve QOL outcomes.


Hemoglobin Concentration > 10 g/dL but < 12 g/dL
The ASCO/ASH 2007 guidelines recommend that for patients with less severe anemia (> 10 g/dL but < 12 g/dL), the decision to use or not use ESA should be based on clinical circumstances.4 For example, ESAs may be considered in elderly patients with limited cardiopulmonary reserve, cardiac disease or symptomatic angina, limited exercise capacity or energy, or ability to carry out activities of daily living (ADL). RBC transfusion is also an option.


Starting/Escalating Doses of ESAs and Reducing/Discontinuing ESAs

The ASCO/ASH 2007 guidelines for ESA dosing and adjustments are based on the US FDA recommendations (Table 1).4

Click to enlarge

Starting and Escalating Doses
The starting dose for epoetin is 150 U/kg 3 times a week and the dose can be increased to 300 U/kg 3 times a week if there is no reduction in transfusion requirement or increase in Hgb after 8 weeks. Epoetin can also be given as 40,000 U weekly and can be increased to 60,000 U weekly if there is < 1 g/dL Hgb increase after 4 weeks.


For darbepoetin, the starting dose is 2.25 ug/kg weekly and the dose can be increased to 4.5 ug/kg if there is < 1 g/dL Hgb increase after 6 weeks. Darbepoetin can also be started at 500 ug every 3 weeks.


Alternative doses or schedules, although they may be more convenient, have not shown differences in outcomes for Hgb response or transfusion.


Reducing Doses
Recommendations for dose reducing ESA call for decreasing the epoetin dose by 25% when the Hgb approaches 12 g/dL or Hgb increases by > 1 g/dL in 2 weeks.


For darbepoetin, recommendations call for reducing the dose by 40% when the Hgb exceeds 11 g/dL or Hgb increases by > 1 g/dL in 2 weeks.


Withholding Doses
If the Hgb exceeds 12 g/dL, the epoetin dose is withheld until Hgb is < 11 g/dL and can be restarted at a 25% reduction from the previous dose.


Likewise, darbepoetin should be withheld if the Hgb exceeds 12 g/dL and until the Hgb is equal to 11 g/dL, but then restarted at a 40% reduction from the previous dose.


If there is no response to ESA, defined as < 1 to 2 g/dL Hgb rise and no reduction in RBC transfusion requirement, after 6 to 8 weeks of treatment, then ESA should be discontinued.


Iron Supplementation with ESAs


The ASCO/ASH 2007 guidelines4 do not differ from the 2002 guidelines3 for iron monitoring and supplementation during ESA treatment. Both sets of guidelines recommend periodic measurements of iron, total iron-binding capacity, transferring saturation, and ferritin levels and iron repletion when indicated. These measurements may be valuable in limiting the use of ESA and maximizing outcomes, but there is not enough evidence to specify the exact timing, frequency, or testing regimens for this monitoring.


Can Erythropoietic Agents Worsen Outcomes?


The possible benefit of erythropoietic agents has been challenged by two negative studies. In the Breast Cancer Eprex Survival Study (BEST), 939 patients with metastatic breast cancer receiving first-line chemotherapy were randomized to receive epoetin alfa or placebo.10 This study was terminated early because there was a higher mortality in the epoetin arm than in the placebo arm at 12 months. This was attributed to a higher rate of breast cancer progression (6% vs 3%) and higher incidence of fatal thrombotic and vascular events (1% vs 0.2%) in the epoetin alfa treated arm than in the placebo arm.


A study evaluating the effect of epoetin beta on the outcome of head-and-neck cancer patients treated with radiation therapy, also had a negative result.11 In this European multicenter trial, 351 patients with anemia (Hgb < 12 g/dL for women and < 13 g/dL for men) undergoing radiation were randomized to placebo or epoetin beta 300 U/kg 3 times weekly from days 10 to14 prior to and continuing throughout radiation therapy. The therapeutic goal was a normalization of the Hgb to > 14 g/dL in men and > 13 g/dL in women. In this study, the locoregional progression-free survival (PFS) was worse in the epoetin beta-treated group (relative risk [RR] 1.62; P = .0008). Overall survival (OS) was also worse (RR 1.39; P = .02). The incidence of vascular disorders (venous thrombosis, pulmonary embolus, cerebrovascular events, hemorrhage, and hypertension) was higher in the epoetin beta-treated group (11% vs 5%). Interestingly, more than 30% of patients did not receive radiation per protocol. When the data were analyzed for those who did receive radiation, there was no difference in PFS or OS.


The design of these two trials was criticized because the enrolled patients were treated to a higher target Hgb level than the optimal level of 12 g/dL recommended by the National Comprehensive Cancer Network guidelines.12


In March 2007, Amgen reported the results of study 20010103 to the US FDA. This was a randomized phase III trial of darbepoetin vs placebo in a group of 989 patients with malignancies.4 The most common cancers were non–small-cell lung cancer (18%), breast cancer (13%), and prostate cancer (11%). The primary endpoint was the proportion of blood transfusions. Secondary endpoints were first occurrence of transfusion from week 5 to week 17, Hgb change, OS, and safety. There was no difference in transfusion requirement (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.62-1.17). OS was worse in the darbepoetin-treated group (HR 1.30; 95% CI 1.07-1.57; P = .008). There was also an increased incidence of thromboembolic events in the darbepoetin-treated group (3.1% vs 1.3% for placebo). This led to a black-box warning on the prescribing information for epoetin and darbepoetin that ESAs are not indicated for cancer patients who are not receiving chemotherapy or radiotherapy.


What are the potential reasons for the negative outcomes seen with ESA? It is possible that ESAs bind to and activate Epo receptors (EpoRs) on the cell surface of tumors, causing nonerythropoietic responses, such as enhancing tumor growth. Recently, there are several reports on the presence of EpoRs on various tumor types including breast cancer, endometrial cancer, cervical cancer, melanoma, lung cancer, papillary thyroid cancer, and head and neck squamous cancers.14 While ongoing work is evaluating this theory, ESAs should be used judiciously.


The skeleton is a common site of metastasis for many solid tumors, and bone metastasis may occur in more than 60% of patients with metastatic breast cancer.14 Bone metastases often lead to skeletal-related events (SREs), such as pain, pathologic fractures requiring surgery or radiation, cord compression, and hypercalcemia of malignancy. These events are associated with significant morbidities with loss of mobility and social function and a decrease in QOL.15 Pathologic fractures are the most common SREs.


Bisphosphonates inhibit osteoclast-mediated bone resorption and have been used to improve outcomes in patients with bone metastasis from solid tumors.16 Patients receiving bisphosphonates may actually experience reduction of pain as well as improvement in mobility and social function. Four bisphosphonates have been approved for treatment of metastatic bone disease in breast cancer. They are pamidronate (Aredia), zoledronic acid (Zometa), ibandronate (Boniva), and clodronate (Bonefos), but only the first two have been approved for use in the United States. Zoledronic acid is the newer of these two bisphosphonates and was approved by the US FDA in 2002.


When to Use Bisphosphonates

ASCO published updated evidence-based guidelines in 2003 on the role of bisphosphonates and bone health in women with breast cancer.17 These guidelines recommend bisphosphonates for breast cancer patients who have evidence of bone destruction on plain radiographs (ie, lytic lesions). Pamidronate at 90 mg over 2 hours or zoledronic acid at 4 mg over 15 minutes intravenously every 3 to 4 weeks may be administered.17


Which of the Available Bisphosphonates Is Better?


Two trials have shown that zoledronic acid has similar efficacy to pamidronate and can be given over a much shorter period of time. The first trial, reported by Berenson et al, compared zoledronic acid against pamidronate in 280 patients with breast cancer or multiple myeloma with lytic bone lesions.18 Patients were randomized to 9 monthly infusions of zoledronic acid at 0.4 mg, 2 mg, or 4 mg, or to pamidronate at 90 mg. The primary endpoint was to determine which dose or doses of zoledronic acid reduced the need for radiation to < 30% of patients. SREs were also evaluated.


Overall, the need for radiation (18% to 21% of patients) was similar in patients treated with pamidronate and zoledronic acid at higher doses of 2 mg and 4 mg, but more patients (24%) treated with the lower, 0.4 mg dose of zoledronic acid required radiation. Furthermore, the rate of SREs was lower (30% to 35%) in patients treated with pamidronate and 2 mg or 4 mg of zoledronic acid than in patients treated with 0.4 mg of zoledronic acid treated group (46%). This phase II trial was not powered to show superiority of zoledronic acid over pamidronate.


The second trial was a phase III that compared pamidronate against zoledronic acid at 4 or 8 mg doses every 3 to 4 weeks in patients with breast cancer or multiple myeloma with lytic bone disease.19 This trial included 1,130 breast cancer patients who were evaluated for 13 months. The primary goal of the study was to show noninferiority or equivalence of zoledronic acid to pamidronate. The secondary endpoints were to evaluate pain and performance status.


Due to more renal problems (creatinine elevation) in patients initially taking the 8 mg dose of zoledronic acid, the dose was reduced to 4 mg. Still, the frequency of serious renal adverse events was higher among those initially receiving the higher dose of zoledronic acid, 1.9% vs 0.5% for patients taking the lower dose throughout the study. Among patients in the pamidronate group, the frequency of serious renal adverse events was 0.2%. Overall, there was no difference in the SRE rate between the zoledronic acid group (46% to 48%) and the pamidronate group (49%), and the median overall survival was about 25 months in each group. Both bisphosphonates had similar effects on pain and performance status.


Bisphosphonates and Renal Dysfunction


The ASCO 2003 guidelines state that in patients with pre-existing renal disease and serum creatinine < 3 mg/dL, no changes are needed in dose, infusion time, or interval of infusion of pamidronate or zoledronic acid.17 Pamidronate should not be given in < 2 hours and zoledronic acid should not be administered in <15 minutes. Due to its shorter infusion time, zoledronic acid is more commonly used than pamidronate. Serum creatinine should be monitored prior to each infusion.


Full doses of bisphosphonates can be given to patients with creatinine clearance > 60 mL/min.20 Table 2 lists the recommended IV zoledronic acid dosing schedules for patients with varying degrees of renal functions.21

Click to enlarge


There are no specific limitations on the use of bisphosphonates in the elderly population. The International Society of Geriatric Oncology task force reviewed the literature on this subject and recommended that creatinine clearance should be used to monitor renal function rather than serum creatinine, which can be misleading in elderly patients.22 Hydration should be optimized, particularly in this population.


The presence of unexplained renal dysfunction is cause for discontinuing pamidronate and zoledronic acid. Unexplained renal dysfunction is defined as a rise in creatinine of ≥ 0.5 mg/dL or an absolute value of more than 1.4 mg/dL among those with normal baseline creatinine. These patients should be re-evaluated every 3 to 4 weeks and pamidronate or zoledronic acid may be reinstituted with caution when the renal function returns to baseline.


Bisphosphonates and Biochemical Markers


The use of biochemical makers is not recommended as part of routine care in patients receiving bisphosphonates.17 Biochemical markers reflect bone resorption. Immunoassays can measure the N-terminal and C-terminal peptides of type I collagen in the urine and serum.23 Preliminary data show that urinary N-telopeptide (NTX) correlates with the extent of bone disease and progression24 and was also found to be associated with future SRE, bone progression, and death.25 However, there is not enough data to support the use of resorption biochemical markers to guide treatments with bisphosphonates.


Role of Bisphosphonates in Controlling Bone Pain


The ASCO 2003 guidelines state that pamidronate or zoledronic acid when used in conjunction with systemic chemotherapy and/or hormonal therapy may be beneficial in relieving pain caused by bone metastases.17 The standard of care in pain management should be instituted, using modalities such as analgesics, steroids, anti-inflammatory agents, local radiation therapy, and systemic radiopharmaceuticals.


Duration of Bisphosphonates


The ASCO 2003 guidelines suggest continuing bisphosphonates until evidence of substantial decline in the patient’s clinical status, based on clinical judgment.17 However, there are no data to address the consequences of stopping bisphosphonates after prior SREs. In an ongoing clinical trial to address the duration question, patients who have had at least 9 doses of a bisphosphonate (pamidronate or zoledronic acid) are randomized to receive either no further therapy, zoledronic acid monthly for a year, or zoledronic acid every 3 months for a year.26 The endpoints are to evaluate the rate of SRE as well as adverse events including osteonecrosis of the jaw (ONJ).


The etiology of ONJ is unclear and likely multifactorial. There is a significant association between dental and jaw trauma and ONJ, with about 60% of cases occurring after dental surgery.26 The risk of ONJ seems to be dose and duration dependent.26 Actinomyces has been frequently found in lesions of ONJ, suggesting possible osteomyelitis at the sites of dental trauma.27 It is not unknown how long to withhold bisphosphonate when a dental procedure is considered. The optimal duration of bisphosphonate use is not clear, but hopefully the ongoing clinical trial can answer this question.

Fatigue Management

Fatigue is one of the most common symptoms experienced by cancer patients, whether the pain is related to the disease or the treatment or both. Fatigue often begins before the cancer diagnosis, increases during the course of cancer treatment, and usually persists after treatment is completed.28 The National Comprehensive Cancer Network Fatigue Guidelines Committee defined cancer-related fatigue (CRF) as “an unusual, persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual function.”29


Fatigue has both subjective and objective components and may cause dysfunctions in physical symptoms, mood, cognition, and social functions. There is some evidence that potential causes of CRF include anemia, vagal afferents, cytokines, circadian rhythm, and the function of the hypothalamic-pituitary-adrenal axis.30 In treating the cancer itself, these other potential causes of fatigue should be taken into account and appropriate treatments offered for anemia, infection, pain, sleep disorders, and psychological disorders such as depression and anxiety. When fatigue persists despite treating the potential culprits, consider nonpharmacologic approaches such as improved nutritional management and exercise.


Since the cause of fatigue is usually multifactorial, the management of fatigue is a challenging problem often viewed by caregivers as an inevitable consequence of cancer and its treatments. Nevertheless, we should do our best to recognize CRF and treat identifiable causes.

Pain Management

Pain is another symptom that is extremely common and usually chronic in cancer patients. About 33% of cancer patients experience some form of pain during active treatment for cancer and more than 75% have pain during the last stages of the disease.31

There are different forms of pain and many can be controlled with traditional analgesics such as opioids and nonsteroidal anti-inflammatory agents. Adjuvant analgesics are also available and are often used as first-line treatment in nonmalignant chronic pain and as second-line treatment when opioid therapy has been optimized.32


Indications for these adjuvant analgesics are:


  • bone pain-steroids, calcitonin (Calcimar, Cibacalcin, Miacalcin), bisphosphonates, radiopharmaceuticals;

  • neuropathic pain-anticonvulsants, local anesthetics, topical anesthetics;

  • musculoskeletal pain-muscle relaxants, benzodiazepines; and

  • pain from bowel obstruction-octreotide (Sandostatin), anticholinergics, steroids.33

Thus, there are a variety of drugs available to treat pain associated with cancer and cancer treatment, and we should do our best to optimize pain management to improve patients’ quality of life.

Psychological Care

The diagnosis of cancer is a frightening experience with fears that life itself is threatened. Patients often have a complexity of physical symptoms associated with cancer and its treatment (fatigue, pain, nausea, anorexia), psychological stress of the cancer illness (depression, anxiety), and the social interaction with family, friends, and the work environment (Figure 1).


Click to enlarge

Psycho-oncology is a defined subspecialty of oncology that deals with several psychological dimensions of cancer, including the psychological impact of cancer on patients and their families and the clinical staff.34 The continuum of cancer illness extends from the diagnosis, to curative treatment, and to survivorship and in many cases, also to disease recurrence with chronic therapies and to end-of-life care. These last phases of treatment are palliative and focused primarily on maximizing comfort measures such as managing pain, depression, and anxiety.


A psycho-oncology service may be available in some cancer centers and community hospitals and can be a valuable resource throughout all phases of care, including end-of-life. Palliative care may be the most emotionally difficult phase of cancer treatment not only for the patients and families, but also for the clinical staff.


The management of metastatic breast cancer has improved in recent years through the introduction of improved therapeutics and supportive care. This E-Update highlighted some of the important areas, as summarized below:

Erythropoiesis-Stimulating Agents (ESAs)

  • Epoetin and darbepoetin are equivalent in terms of hematologic response rates, transfusion rates, and thromboembolic risks.

  • ESA may be initiated for chemotherapy-induced anemia when Hgb is approaching or < 10 g/dL. ESA may be initiated for milder anemia with Hgb > 10 g/dL and < 12 g/dL based on clinical circumstances (ie, elderly patients with limited cardiopulmonary reserve or significantly reduced exercise capacity, energy, or ability to carry out activities of daily living). Dose adjustments may be made according to Hgb response (Table 1).

  • ESAs are administered only to avoid red blood cell transfusions in cancer patients. ESAs do not improve the outcome of cancer treatment.

  • Do not use ESAs to target Hgb to > 12 g/dL.

  • ESAs are not indicated for patients not undergoing chemotherapy or radiation therapy. ESAs increased the risk of death in this patient population.



  • Bisphosphonates (pamidronate or zoledronic acid) are recommended for patients with lytic bone lesions. Both are equally efficacious.

  • There is a small risk of renal dysfunction with bisphosphonates, so the standard infusion time should be followed (4 mg zoledronic acid at 15-minute infusion time and 90 mg pamidronate at 2-hour infusion time). Serum creatinine should be monitored prior to each infusion. Full doses of bisphosphonates may be used in patients with creatinine clearance > 60 mL/minutes. Dose adjustments should be made for those with a lower creatinine clearance (Table 2).

  • The duration of bisphosphonate therapy is unclear. A clinical trial is ongoing to answer this question.

While life-extending treatments (with chemotherapy, hormonal therapy, or biologic and targeted therapies) and adjunctive treatments (with ESAs and bisphosphonate) are important, it is equally important to optimize management of fatigue and pain and provide psychological support to our patients.


CME Post-Test and Evaluation





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  • Rizzo JD, Lichtin AE, Woolf SH, et al: Use of epoetin in patients with cancer: Evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 20:4083-4107, 2002.

  • Rizzo JD, Somerfield MR, Hagerty KL, et al: American Society of Clinical Oncology/American Society of Hematology 2007 Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin. J Clin Oncol 25:1-17, 2007.

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  • Crawford J, Robert F, Perry MC, et al: A randomized trial comparing immediate versus delayed treatment of anemia with once-weekly epoetin alfa in patients with non-small cell lung cancer scheduled to receive first-line chemotherapy. J Thorac Oncol 2:210-220, 2007.

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  • Rearden TP, Charu V, Saidman B, et al: Results of a randomized study of every three-week dosing (Q3W) of darbepoetin alfa or chemotherapy-induced anemia (CIA) (abstract 8064). J Clin Oncol 22:745a, 2004.

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  • Henke M, laszig R, Rube C, et al: Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: Randomized, double-blind, placebo-controlled trial. Lancet 362:1255-1260, 2003.

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  • Berenson JR, Rosen LS, Howell A, et al: Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 91:1191-1200, 2001.

  • Rosen LS, Gordon D, Kaminski M, et al: Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: A randomized, double-blind, multicenter, comparative trial. Cancer 98:1735-1744, 2003.

  • Zometa® (zoledronic acid) US summary of product characteristics. East Hanover, NJ: Novartis Pharmaceuticals Corporation, 2004.

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  • Body JJ, Coleman R, Clezardin P, et al: International Society of Geriatric Oncology (SIOG) clinical practice recommendations for the use of bisphosphonates in elderly patients. Eur J Cancer 43:852-858, 2007.

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