Complications of Multiple Myeloma Therapy, Part 1: Risk Reduction and Management of Peripheral Neuropathy and Asthenia

Peripheral neuropathy (PN) and asthenia (fatigue) occur as both disease- and treatment-related complications in patients with multiple myeloma (MM). Risk factors for treatment-related PN, which has an estimated incidence of 37% to 83% among patients with MM, include therapy duration, dose intensity, cumulative dose, and the presence of preexisting neuropathy. Asthenia is the most common adverse effect of treatment, occurring in approximately 76% to 96% of patients receiving therapy. The severity of PN and asthenia can range from mild to potentially debilitating. These conditions can be dose limiting; they may interfere with optimizing duration of therapy and may also substantially affect patient quality of life. Regular screening and monitoring, combined with patient education and effective management strategies, can reduce the risk of these treatment-related complications, as well as their consequences.

Abstract

Peripheral neuropathy (PN) and asthenia (fatigue) occur as both disease- and treatment-related complications in patients with multiple myeloma (MM). Risk factors for treatment-related PN, which has an estimated incidence of 37% to 83% among patients with MM, include therapy duration, dose intensity, cumulative dose, and the presence of preexisting neuropathy. Asthenia is the most common adverse effect of treatment, occurring in approximately 76% to 96% of patients receiving therapy. The severity of PN and asthenia can range from mild to potentially debilitating. These conditions can be dose limiting; they may interfere with optimizing duration of therapy and may also substantially affect patient quality of life. Regular screening and monitoring, combined with patient education and effective management strategies, can reduce the risk of these treatment-related complications, as well as their consequences.

Peripheral neuropathy (PN) and asthenia (fatigue) are among the most commonly seen complications in patients undergoing multiple myeloma (MM) therapy. These potentially debilitating adverse effects are frequently dose limiting, and they may interfere with optimal therapy and substantially affect patient quality of life as well as outcome. Effective strategies for preventing and managing these complications of MM therapy are thus critical.

Peripheral Neuropathy
Overview

PN occurs in MM both as a disease-related complication in newly diagnosed patients and as a side effect of MM therapy. The reported incidence is 1% to 20% in untreated patients with MM and 37% to 83% in previously treated individuals; neurophysiologic evidence of neuropathy may be detected in 11% to 52% and 39% to 46% of these populations, respectively.16 Risk factors for PN include treatment-specific characteristics, such as therapy duration, dose intensity, and cumulative dose, and patient-specific factors, such as age, comorbidities (e.g., diabetes mellitus, alcoholism), and the presence of preexisting neuropathy.4,611

Clinical Features

Treatment-related PN depends on the agents used, as described subsequently, and is typically a length-dependent, axonal, sensory, or mixed sensorimotor neuropathy with symmetric, distal, and progressive signs and symptoms. Clinical manifestations are usually agent-specific but range from temporary numbness, paresthesia, dysesthesia, hyperesthesia, loss of deep tendon reflexes, and muscle weakness or cramps to burning pain, muscle wasting, and paralysis. Autonomic involvement may result in orthostatic hypotension, constipation/ileus, and urinary bladder or sexual dysfunction. In the most extreme cases, the manifestations of treatment-related PN can be life-threatening but this is, fortunately, very rare.7,9,12

Thalidomide-Induced PN (TiPN)

Thalidomide has been shown to produce a small- and large-fiber sensory PN with distal symmetric loss of all modalities, primarily affecting the lower limbs. Associated clinical signs and symptoms typically include tingling or painful paresthesias and numbness in the feet and sometimes the hands.1,5,7,9,13 Motor neuropathy occurs infrequently with thalidomide treatment; if present, it is usually mild in severity.9,14 Autonomic manifestations are common, and include gastrointestinal (e.g., constipation, anorexia, nausea) as well as cardiovascular (e.g., hypotension, bradycardia) effects.1517 Although the symptoms of thalidomide-induced PN are usually reversible after dose reduction or treatment stoppage, some effects may be permanent.15,17

Table 1

National Cancer Institute Common Toxicity Criteria (Version 3) for Peripheral Neuropathy

Table 1

The incidence of thalidomide-induced PN varies among different patient populations, treatment regimens, and diagnostic criteria, but estimates range from 37% to 83%.1,5,9,13,1521 Most cases are mild to moderate, classified as grades 1 to 2 (Table 1).22 Evidence from numerous studies indicates that the risk and severity of thalidomide-induced PN increases with cumulative dose or treatment duration, particularly when therapy extends beyond 6 months,1,5,7,1517,19,23 although neurotoxicity can also occur with short-term exposure.

Bortezomib-Induced PN (BiPN)

Bortezomib-induced PN is predominantly a small-fiber sensory neuropathy, characterized by distal symmetric loss of all modalities in the lower limbs.3,9,24,25 Clinical signs and symptoms include burning dysesthesia, numbness, hyperesthesia, and pain; effects are typically more pronounced in the lower limbs.9,25 Motor involvement is less likely with bortezomib than with thalidomide, but it may result in mild distal lower limb weakness.9 Autonomic dysfunction is frequently observed with bortezomib-induced PN; clinical manifestations include gastrointestinal adverse effects (e.g., diarrhea, nausea, constipation, vomiting, anorexia) and hypotension.25,26 The neurotoxic effects of bortezomib therapy are generally reversible with dose reduction or treatment discontinuation.3,4,11,14,24,2731

The distinctive clinical features of bortezomib-associated neuropathy suggest fundamental differences in its pathogenesis compared with thalidomide and other agents.9,24,25,28 Findings from recent in vitro and in vivo studies suggest that proteasome inhibitor-induced PN may be mechanism-based (a consequence of proteasome inhibition itself), with dorsal root ganglia identified as a primary target leading to secondary peripheral nerve degeneration.32 However, a seperate preclinical study suggested that the dorsal root ganglia lesions seen with bortezomib administration did not occur with carfilzomib, a second-generation proteasome inhibitor currently being investigated for the treatment of MM, although other studies have suggested carfilzomib, and agents in its class do in fact cause dorsal root ganglion abnormality.32,33 Further research is necessary to determine whether the mechanism underlying bortezomib-induced PN represents a class effect of proteasome inhibitors. However, clinical studies to date suggest this to be true, but with the degree of PN being less with carfilzomib.34

The reported incidence of treatment-emergent PN with bortezomib is 31% to 64%, with severe (grade 3 or 4) symptoms seen in 3% to 22% of patients.3,4,6,11,2731,3537 Evidence of the dose-related and cumulative nature of bortezomib-induced neurotoxicity has been provided in several phase II and III studies, with reversibility also demonstrated in each of these.4,11,24,2729,35,38

Assessment/Monitoring

A comprehensive neuropathy assessment may involve a combination of patient history, clinical neurologic examination, and neurophysiologic testing. Diagnosis of any underlying conditions or comorbidities that may increase the risk of treatment-related PN is a critical part of this evaluation. PN severity should be characterized at each assessment to monitor neuropathy progression and determine whether a regimen change or some other type of intervention is indicated. Patient education is important for improving awareness and encouraging the reporting of symptoms. Neurotoxicity assessment tools (see an example in Figure 1) may be useful for quantifying PN severity based on patient self-reports.12

Patients should be evaluated for evidence of neuropathy at baseline, before initiating a change in therapeutic regimen, in conjunction with new or worsening signs or symptoms, and periodically throughout treatment. Patient- or agent-specific risk factors may necessitate more aggressive or targeted assessments. For example, because the incidence of thalidomide-induced PN has been reported to increase with longer duration of administration; monthly evaluation of patients is recommended during the first 3 months of treatment and regularly thereafter.15 In addition, neurophysiologic testing is suggested (e.g., sensory nerve action potential amplitudes) every 6 months for the detection of asymptomatic PN.15

Management Strategies

Dose Reduction and Schedule Modification: For patients with grade 1 PN, thalidomide therapy may be continued with a 50% dose reduction, particularly if no other treatment options are available.17 For grade 2 PN, thalidomide therapy should be discontinued until neuropathy has returned to baseline or less than a grade 1 severity; treatment may subsequently be resumed with dosage levels reduced by half.17 Some recommend restricting thalidomide therapy to short-term use (e.g., < 6 months) or low-dose regimens (e.g., 50 mg/d).5,18 In general, a conservative PN management approach is recommended for newly diagnosed MM patients, especially when treatment alternatives exist.17 Bortezomib dose modifications should be made according to the directions in the prescribing information,25 which are based on PN severity and the degree of associated neuropathic pain or impaired function (Table 2). The benefits of dose modification were shown in the pivotal phase III trial of bortezomib, with resolution or improvement of grade 2 or higher PN observed in 68% of patients who underwent a prespecified dose-reduction protocol, compared with 47% of those who did not.28

Therapeutic Intervention: Nonpharmacologic management of sensory PN symptoms or neuropathic pain may involve the use of daily vitamins and nutritional supplements (e.g., multi-B complex vitamins [B1, B6, B12], folic acid, magnesium, potassium, vitamin E, acetyl l-carnitine, α-lipoic acid, l-glutamine; see Table 3 for dosing), emollient creams (e.g., cocoa butter, menthol, and eucalyptus-based creams), and physical therapy, as well as therapeutic massage.12,3943 These recommendations are largely based on anecdotal evidence, and controlled studies are needed to confirm their efficacy. Moreover, use of supplements on the day of bortezomib administration is not recommended based upon preclinical data suggesting the possibility of antagonism, although this has not been confirmed clinically.44

If symptoms are inadequately controlled with nonpharmacologic intervention alone, pharmacologic therapy is advised. Because response is likely to vary substantially for each individual, a stepwise process may be necessary.41,45 Evidence of the therapeutic benefits of many pharmacologic agents used in the treatment of neuropathic pain comes primarily from short-term clinical studies, so the long-term efficacy of such therapy has not yet been established.45

Figure 1
Figure 1

Tool for assessing severity of peripheral neuropathy. Republished with permission from Oncology Nursing Society. Tariman JD, Love G, McCullagh E, Sandifer S. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs 2008;12(3 Suppl):29–36; permission conveyed through Copyright Clearance Center, Inc.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, Suppl_1; 10.6004/jnccn.2010.0115

Among the pharmacologic agents recommended for the treatment of grade 1 or higher sensory PN or neuropathic pain are gabapentin, pregabalin, nortriptyline, duloxetine, and topical lidocaine. Gabapentin, an anticonvulsant approved by the FDA for the treatment of neuropathic pain associated with postherpetic neuralgia, may be administered at an initial dose of 300 mg, 3 times daily, with titration as tolerated up to 1200 mg, 3 times daily.3

For additional symptomatic relief, the tricyclic antidepressant nortriptyline may be added at an initial dose of 25 mg every night at bedtime; dosing may be increased to 50 mg after 2 weeks, with further dose escalation of 25 mg monthly (as tolerated), up to a maximum of 100 mg every night at bedtime. If patient response remains inadequate, duloxetine, an antidepressant FDA approved for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, may be prescribed at a dose of 20 to 60 mg every day. Topical lidocaine, which is FDA approved for postherpetic neuralgia, is sometimes helpful for the control of neuropathic pain in the feet and hands.

Table 2

Bortezomib Dose Modification Based on Severity of Bortezomib-Induced Peripheral Neuropathy

Table 2
Future Directions

The use of newer MM agents with improved neurotoxicity profiles can reduce the risk of treatment-related PN. Phase III trials have shown that with the potent thalidomide analogue lenalidomide, the incidence of grade 3 or 4 PN is less than 3%.46,47 The risk of treatment-emergent PN also appears to be decreased with the second-generation proteasome inhibitors carfilzomib (PR-171)48 and salinosporamide A (NPI-0052).49

The risk of treatment-related PN may also be reduced by combining agents that have synergistic or neuroprotective effects. For example, a number of investigations have provided evidence of the potential synergy between proteasome inhibitors and immunomodulatory agents in terms of anti-tumor effect.50 Importantly, while neuropathy as a treatment-related side effect is a concern with this combination, the severity of PN has been less than expected. Specifically, studies have shown that the incidence of grade 3 PN is 5% to 10% with bortezomib/thalidomide/dexamethasone combination therapy.31,5153 Importantly, no occurrences of grade 4 PN and only 1 case of grade 3 PN have been seen in a phase I/II study of lenalidomide/bortezomib/dexamethasone (RVD) in 66 subjects with newly diagnosed MM.52 In a phase II trial of RVD treatment in 64 patients with relapsed and/or refractory MM, only 1 case of grade 3 PN was seen, which occurred despite bortezomib reduction and required treatment discontinuation but subsequent improvement followed.54 This suggests that such combinations may favorably influence at least the severity of PN, perhaps through an anti-inflammatory mechanism, as well as allowing dose reduction without loss of therapeutic effect.

Initial findings suggest that the heat shock protein inhibitor tanespimycin may exhibit both synergistic and neuroprotective effects when combined with bortezomib for treatment of MM. In a phase I/II study, no cases of grade 3/4 treatment-emergent PN were detected in 72 patients treated with bortezomib plus tanespimycin for relapsed and refractory MM.55

Asthenia

Asthenia, commonly referred to as fatigue, has been defined as a “distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion” that is not proportional to recent activity, interferes with usual functioning, and is not relieved by rest.56,57 Its symptoms can also include generalized weakness, lack of energy, and malaise. Many MM patients with asthenia have comorbidities such as depression, anxiety, and impaired psychosocial functioning, which can be exacerbated by medication effects, especially in combination with glucocorticoids.

Asthenia is a highly prevalent condition among patients with cancer in general and the most common side effect of cancer treatment.58 Clinical trial data suggest that asthenia of any grade affects approximately 40% to 75% of patients with newly diagnosed disease, 60% to 93% of individuals treated with radiotherapy, and 76% to 96% of patients treated with chemotherapy, depending on the type of primary neoplasia and treatment regimen.5862 Examples of MM-specific rates in phase III trials are grade 3/4 asthenia has been reported by 15% of newly diagnosed patients receiving thalidomide/dexamethasone,20 by about 6% of patients with relapsed–refractory disease receiving bortezomib,29 by 6% of patients with relapsed–refractory disease receiving bortezomib/liposomal doxorubicin,63 and by 10% of newly diagnosed patients receiving lenalidomide/low-dose dexamethasone.64 The results of patient surveys suggest that asthenia exerts a more negative and longer-lasting effect on patients than pain, nausea, or depression, but that treatment is prescribed in as few as 14% to 40% of cases.59,62 This is true even though asthenia may persist for months or even years after treatment is completed.

Table 3

Suggested Doses of Some Commonly Used Vitamins/Supplements for PN*

Table 3

According to the NCCN Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue (to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org), every cancer patient should be screened for asthenia at regular intervals, in conjunction with other vital-sign monitoring.56 During the initial screening, patients should be asked to assess their level of fatigue during the previous 7-day period, using a predefined scale. A comprehensive primary asthenia examination is recommended for all patients reporting moderate to severe fatigue. No standardized guidelines for diagnosis of asthenia have been established, but the Tenth Revision of the International Classification of Disease (ICD-10) includes a proposed set of diagnostic criteria (Table 4).65

Management approaches for asthenia include 1) treatment of contributing factors (e.g., anemia, pain, depression/anxiety, systemic disorders, such as hypothyroidism, sleep disturbances, nutritional deficiencies, and medication side effects); 2) patient education regarding the causes of asthenia and general strategies for fatigue self-management; 3) nonpharmacologic interventions, including counseling, occupational therapy, cognitive behavioral therapy, exercise, dietary changes, and stress management; and 4) pharmacologic symptomatic therapy.56 Clinical trial data and anecdotal evidence suggest that psychostimulants, low-dose corticosteroids, and antidepressants may be helpful,66 but psychostimulants are investigational for this purpose and should be used with caution only after treatment- and disease-specific morbidities have been characterized or excluded. The optimal dose and schedule have not been established for use of psychostimulants in cancer patients. Specific measures in MM patients include attention to hydration, evaluation of novel-agent specific–effects (such as those seen with bortezomib, thalidomide, and lenalidomide); exclusion of important co-morbidities (e.g., thyroid deficiency, amyloidosis), and care regarding the possibility of progressive disease.67

Table 4

ICD-10 Criteria for Cancer-Related Fatigue

Table 4
Conclusions

Peripheral neuropathy and asthenia are frequent complications of MM treatment. These complications interfere with optimum therapy and adversely affect patient outcomes as well as quality of life. Among novel therapies associated with significant PN are bortezomib and thalidomide, both agents that have transformed the MM treatment paradigm through improvements in response rates, time-to-progression, and survival. Novel combination therapies for MM have the potential to reduce side effects, as well as enhance activity, thus improving the therapeutic index.68 In addition, effective management strategies are critical to reduce the risk of further treatment-related toxicities and improve the benefits of therapy in this otherwise incurable malignancy.

The authors thank Kimberly Cohen for medical writing assistance and Katherine Redman for administrative support. The authors also gratefully acknowledge the input of Kathleen Colson, RN, and Deborah Doss, RN.

Supported by an educational grant from Millennium Pharmaceuticals, Inc.

References

  • 1.

    PlasmatiRPastorelliFCavoM. Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology2007;69:573581.

  • 2.

    ChaudhryVCornblathDRPolydefkisM. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst2008;13:275282.

    • Search Google Scholar
    • Export Citation
  • 3.

    RichardsonPGXieWMitsiadesC. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol2009;27:35183525.

    • Search Google Scholar
    • Export Citation
  • 4.

    RichardsonPGBriembergHJagannathS. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol2006;24:31133120.

    • Search Google Scholar
    • Export Citation
  • 5.

    MileshkinLStarkRDayB. Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol2006;24:45074514.

    • Search Google Scholar
    • Export Citation
  • 6.

    BadrosAGoloubevaODalalJS. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer2007;110:10421049.

    • Search Google Scholar
    • Export Citation
  • 7.

    WickhamR. Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clin J Oncol Nurs2007;11:361376.

    • Search Google Scholar
    • Export Citation
  • 8.

    WolfJRichardsonPGSchusterM. Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series. Clin Adv Hematol Oncol2008;6:755760.

    • Search Google Scholar
    • Export Citation
  • 9.

    WindebankAJGrisoldW. Chemotherapy-induced neuropathy. J Peripher Nerv Syst2008;13:2746.

  • 10.

    PalumboARajkumarSV. Treatment of newly diagnosed myeloma. Leukemia2009;23:449456.

  • 11.

    MateosMVRichardsonPSchlagR. Peripheral neuropathy with VMP resolves in the majority of patients and shows a rate plateau [abstract]. Presented at the XII International Myeloma Workshop; February 26–March 1 2009; Washington D.C. Abstract 172.

    • Search Google Scholar
    • Export Citation
  • 12.

    TarimanJDLoveGMcCullaghESandiferSfor the IMF Nurse Leadership Board. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs2008;12(3 Suppl):2936.

    • Search Google Scholar
    • Export Citation
  • 13.

    MileshkinLPrinceHM. The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma2006;47:22762279.

  • 14.

    KannarkatGLasherEESchiffD. Neurologic complications of chemotherapy agents. Curr Opin Neurol2007;20:719725.

  • 15.

    Thalomid package insert. Summit, NJ: Celgene Corporation; 2007.

  • 16.

    PalumboAFaconTSonneveldP. Thalidomide for treatment of multiple myeloma: 10 years later. Blood2008;111:39683977.

  • 17.

    GhobrialIMRajkumarSV. Management of thalidomide toxicity. J Support Oncol2003;1:194205.

  • 18.

    OffidaniMCorvattaLMarconiM. Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy. Eur J Haematol2004;72:403409.

    • Search Google Scholar
    • Export Citation
  • 19.

    RichardsonPSchlossmanRJagannathS. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc2004;79:875882.

    • Search Google Scholar
    • Export Citation
  • 20.

    RajkumarSVBloodEVesoleD. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol2006;24:431436.

    • Search Google Scholar
    • Export Citation
  • 21.

    RajkumarSVRosiñolLHusseinM. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol2008;26:21712177.

    • Search Google Scholar
    • Export Citation
  • 22.

    National Cancer Institute. Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. Version 3.0 [Web page]. August 9 2006. Available at: http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed August 28 2009.

    • Search Google Scholar
    • Export Citation
  • 23.

    CavalettiGBeronioAReniL. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study. Neurology2004;62:22912293.

  • 24.

    RichardsonPJagannathSColsonK. Optimizing the efficacy and safety of bortezomib in relapsed multiple myeloma. Clin Adv Hematol Oncol2006;4(5 Suppl 13):18.

    • Search Google Scholar
    • Export Citation
  • 25.

    Velcade package insert. Cambridge, MA: Millennium Pharmaceuticals, Inc; 2008.

  • 26.

    CrocchioloRFerrariSCalbiV. Effect of bortezomib on the autonomic nervous system [abstract]. Presented at the 2006 American Society of Hematology Annual Meeting; December 9–12 2006; Orlando Florida. Abstract 5101.

    • Search Google Scholar
    • Export Citation
  • 27.

    RichardsonPGBarlogieBBerensonJ. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med2003;348:26092617.

  • 28.

    RichardsonPGSonneveldPSchusterMW. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol2009;144:895903.

    • Search Google Scholar
    • Export Citation
  • 29.

    RichardsonPGSonneveldPSchusterMW. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med2005;352:24872498.

    • Search Google Scholar
    • Export Citation
  • 30.

    El-CheikhJStoppaAMBouabdallahR. Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma. Clin Lymphoma Myeloma2008;8:146152.

    • Search Google Scholar
    • Export Citation
  • 31.

    CaravitaTPetrucciMTSpagnoliA. Neuropathy in multiple myeloma patients treated with bortezomib: a multicenter experience [abstract]. Presented at the 2007 American Society of Hematology Annual Meeting; December 8–11 2007; Atlanta Georgia. Abstract 4823.

    • Search Google Scholar
    • Export Citation
  • 32.

    SilvermanLCsizmadiaVBrewerK. Proteasome inhibitor associated neuropathy is mechanism based [abstract]. Annual Meeting of the American Society of Hematology. 2008. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 2646.

    • Search Google Scholar
    • Export Citation
  • 33.

    KirkCJJiangJMuchamuelT. The selective proteasome inhibitor carfilzomib is well tolerated in experimental animals with dose intensive administration [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 2765.

    • Search Google Scholar
    • Export Citation
  • 34.

    JagannathSVijRStewartAK. The Multiple Myeloma Research Consortium (MMRC). Initial results of PX-171-003, an open-label, single-arm, phase II study of carfilzomib (CFZ) in patients with relapsed and refractory multiple myeloma (MM) [abstract]. Blood2008;112:Abstract 864.

    • Search Google Scholar
    • Export Citation
  • 35.

    JagannathSBarlogieBBerensonJ. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol2004;127:165172.

    • Search Google Scholar
    • Export Citation
  • 36.

    RichardsonPGHideshimaTMitsiadesCAndersonK. Proteasome inhibition in hematologic malignancies. Ann Med2004;36:304314.

  • 37.

    DhawanRDelforgeMDe SamblanxH. Peripheral neuropathy as assessed in an international observational study of bortezomib [abstract]. Presented at the XII International Myeloma Workshop; February 26–March 1 2009; Washington D.C. Abstract 134.

    • Search Google Scholar
    • Export Citation
  • 38.

    San MiguelJFSchlagRKhuagevaNK. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med2008;359:906917.

    • Search Google Scholar
    • Export Citation
  • 39.

    ColsonKDossDSSwiftRTarimanJ. Expanding role of bortezomib in multiple myeloma: nursing implications. Cancer Nurs2008;31:239249.

  • 40.

    SmithGG. Proteasome inhibition in cancer therapy. J Infus Nurs2005;28:258264.

  • 41.

    DworkinRHO'ConnorABBackonjaM. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain2007;132:237251.

  • 42.

    JensenTSFinnerupNB. Management of neuropathic pain. Curr Opin Support Palliat Care2007;1:126131.

  • 43.

    ColvinLAJohnsonPRMitchellR. From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J Clin Oncol2008;26:45194520.

    • Search Google Scholar
    • Export Citation
  • 44.

    PerroneGHideshimaTIkedaT. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia2009;23:16791686

  • 45.

    ZinCSNissenLMSmithMT. An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy. CNS Drugs2008;22:417442.

    • Search Google Scholar
    • Export Citation
  • 46.

    WeberDMChenCNiesvizkyR. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med2007;357:21332142.

    • Search Google Scholar
    • Export Citation
  • 47.

    DimopoulosMSpencerAAttalM. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med2007;357:21232132.

    • Search Google Scholar
    • Export Citation
  • 48.

    JagannathSVijRStewartK. Final results of PX-171-003-A0 part 1 of an open-label single-arm phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8504.

    • Search Google Scholar
    • Export Citation
  • 49.

    HofmeisterCCRichardsonPZimmermanT. Clinical trial of the novel structure proteasome inhibitor NPI-0052 in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8505.

    • Search Google Scholar
    • Export Citation
  • 50.

    MitsiadesNMitsiadesCSPoulakiV. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood2002;99:45254530.

    • Search Google Scholar
    • Export Citation
  • 51.

    WangMGiraltSDelasalleK. Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple myeloma. Hematology2007;12:235239.

    • Search Google Scholar
    • Export Citation
  • 52.

    ZangariMBarlogieBBurnsMJ. Velcade-thalidomide-dexamethasone for advance and refractory multiple myeloma: long-term follow-up of phase I-II trial UARK 2001-37: superior outcome in patients with normal cytogenetics and no prior thalidomide [abstract]. Presented at the 2005 American Society of Hematology Annual Meeting; December 10–13 2005; Atlanta Georgia. Abstract 2552.

    • Search Google Scholar
    • Export Citation
  • 53.

    RichardsonPLonialSJakubowiakA. Lenalidomide bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma: encouraging efficacy in high risk groups with updated results of a phase I/II study [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 92.

    • Search Google Scholar
    • Export Citation
  • 54.

    RichardsonPJagannathSJakubowiakA. Lenalidomide bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma: encouraging response rates and tolerability with correlation of outcome and adverse cytogenetics in a phase II study [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 1742.

    • Search Google Scholar
    • Export Citation
  • 55.

    RichardsonPGChanan-KhanALonialS. Tanespimycin plus bortezomib in patients with relapsed and refractory multiple myeloma: final results of a phase I/II study [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8503.

    • Search Google Scholar
    • Export Citation
  • 56.

    BergerAMAbernethyAPAtkinsonA. NCCN clinical practice guidelines in oncology: cancer-related fatigue version 1.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Accessed May 12 2009.

    • Search Google Scholar
    • Export Citation
  • 57.

    MorrowGRShelkeARRoscoeJA. Management of cancer-related fatigue. Cancer Invest2005;23:229239.

  • 58.

    StasiRAbrianiLBeccagliaP. Cancer-related fatigue: evolving concepts in evaluation and treatment. Cancer2003;98:17861801.

  • 59.

    CurtGABreitbartWCellaD. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist2000;5:353360.

    • Search Google Scholar
    • Export Citation
  • 60.

    MorrowGR. Cancer-related fatigue: causes, consequences, and management. Oncologist2007;12(Suppl 1):13.

  • 61.

    HofmanMRyanJLFigueroa-MoseleyCD. Cancer-related fatigue: the scale of the problem. Oncologist2007;12(Suppl 1):410.

  • 62.

    VogelzangNJBreitbartWCellaD. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. Semin Hematol1997;34(3 Suppl 2):412.

    • Search Google Scholar
    • Export Citation
  • 63.

    OrlowskiRZNaglerASonneveldP. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol2007;25:38923901.

    • Search Google Scholar
    • Export Citation
  • 64.

    RajkumarSVJacobusSCallanderN. A randomized trial of lenalidomide plus high-dose dexamethasone vs lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. Presented at the 2007 American Society of Hematology Annual Meeting; December 8–11 2007; Atlanta Georgia. Abstract 74.

    • Search Google Scholar
    • Export Citation
  • 65.

    BreitbartWAlici-EvcimenY. Update on psychotropic medications for cancer-related fatigue. J Natl Compr Canc Netw2007;5:10811091.

  • 66.

    BreitbartWAliciY. Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. Clin J Oncol Nurs2008;12(5 Suppl):2736.

    • Search Google Scholar
    • Export Citation
  • 67.

    LaubachJPMitsiadesCSMahindraA. Novel therapies in the treatment of multiple myeloma. J Natl Compr Cancer Netw2009;7:947960.

  • 68.

    RichardsonPGMitsiadesCSchlossmanR. New drugs for myeloma. Oncologist2007;12:664689.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Paul G. Richardson, MD, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Dana 1B02, Boston, MA 02115. E-mail: paul_richardson@dfci.harvard.edu

Dr. Richardson reports having participated in funded research for Celgene Corporation and Millennium and having participated as an advisory board member or consultant for Celgene Corporation; Millennium Pharmaceuticals, Inc.; and Johnson & Johnson. Dr. Laubach reports no potential conflicts of interest. Dr. Schlossman reports having served as a speakers' bureau member for Celgene Corporation and Millennium Pharmaceuticals, Inc. Dr. Mitsiades reports having participated in funded research for OSI Pharmaceuticals, Inc.; Amgen, Inc.; AVEO Pharmaceuticals, Inc.; EMD Serono, Inc.; and Sunesis Pharmaceuticals, Inc., and having participated as an advisory board member for Millennium Pharmaceuticals, Inc.; Novartis International AG; Merck & Co.; and Pharmion Corporation. Dr. Anderson reports having received preclinical and clinical research support from Millennium Pharmaceuticals, Inc., Celgene Corporation, and Novartis, and having served as an advisory board member for Millennium Pharmaceuticals, Inc., Celgene Corporation, Novartis, and Merck & Co.

Article Sections

Figures

  • View in gallery

    Tool for assessing severity of peripheral neuropathy. Republished with permission from Oncology Nursing Society. Tariman JD, Love G, McCullagh E, Sandifer S. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs 2008;12(3 Suppl):29–36; permission conveyed through Copyright Clearance Center, Inc.

References

  • 1.

    PlasmatiRPastorelliFCavoM. Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology2007;69:573581.

  • 2.

    ChaudhryVCornblathDRPolydefkisM. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst2008;13:275282.

    • Search Google Scholar
    • Export Citation
  • 3.

    RichardsonPGXieWMitsiadesC. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol2009;27:35183525.

    • Search Google Scholar
    • Export Citation
  • 4.

    RichardsonPGBriembergHJagannathS. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol2006;24:31133120.

    • Search Google Scholar
    • Export Citation
  • 5.

    MileshkinLStarkRDayB. Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol2006;24:45074514.

    • Search Google Scholar
    • Export Citation
  • 6.

    BadrosAGoloubevaODalalJS. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer2007;110:10421049.

    • Search Google Scholar
    • Export Citation
  • 7.

    WickhamR. Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clin J Oncol Nurs2007;11:361376.

    • Search Google Scholar
    • Export Citation
  • 8.

    WolfJRichardsonPGSchusterM. Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series. Clin Adv Hematol Oncol2008;6:755760.

    • Search Google Scholar
    • Export Citation
  • 9.

    WindebankAJGrisoldW. Chemotherapy-induced neuropathy. J Peripher Nerv Syst2008;13:2746.

  • 10.

    PalumboARajkumarSV. Treatment of newly diagnosed myeloma. Leukemia2009;23:449456.

  • 11.

    MateosMVRichardsonPSchlagR. Peripheral neuropathy with VMP resolves in the majority of patients and shows a rate plateau [abstract]. Presented at the XII International Myeloma Workshop; February 26–March 1 2009; Washington D.C. Abstract 172.

    • Search Google Scholar
    • Export Citation
  • 12.

    TarimanJDLoveGMcCullaghESandiferSfor the IMF Nurse Leadership Board. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs2008;12(3 Suppl):2936.

    • Search Google Scholar
    • Export Citation
  • 13.

    MileshkinLPrinceHM. The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma2006;47:22762279.

  • 14.

    KannarkatGLasherEESchiffD. Neurologic complications of chemotherapy agents. Curr Opin Neurol2007;20:719725.

  • 15.

    Thalomid package insert. Summit, NJ: Celgene Corporation; 2007.

  • 16.

    PalumboAFaconTSonneveldP. Thalidomide for treatment of multiple myeloma: 10 years later. Blood2008;111:39683977.

  • 17.

    GhobrialIMRajkumarSV. Management of thalidomide toxicity. J Support Oncol2003;1:194205.

  • 18.

    OffidaniMCorvattaLMarconiM. Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy. Eur J Haematol2004;72:403409.

    • Search Google Scholar
    • Export Citation
  • 19.

    RichardsonPSchlossmanRJagannathS. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc2004;79:875882.

    • Search Google Scholar
    • Export Citation
  • 20.

    RajkumarSVBloodEVesoleD. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol2006;24:431436.

    • Search Google Scholar
    • Export Citation
  • 21.

    RajkumarSVRosiñolLHusseinM. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol2008;26:21712177.

    • Search Google Scholar
    • Export Citation
  • 22.

    National Cancer Institute. Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. Version 3.0 [Web page]. August 9 2006. Available at: http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed August 28 2009.

    • Search Google Scholar
    • Export Citation
  • 23.

    CavalettiGBeronioAReniL. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study. Neurology2004;62:22912293.

  • 24.

    RichardsonPJagannathSColsonK. Optimizing the efficacy and safety of bortezomib in relapsed multiple myeloma. Clin Adv Hematol Oncol2006;4(5 Suppl 13):18.

    • Search Google Scholar
    • Export Citation
  • 25.

    Velcade package insert. Cambridge, MA: Millennium Pharmaceuticals, Inc; 2008.

  • 26.

    CrocchioloRFerrariSCalbiV. Effect of bortezomib on the autonomic nervous system [abstract]. Presented at the 2006 American Society of Hematology Annual Meeting; December 9–12 2006; Orlando Florida. Abstract 5101.

    • Search Google Scholar
    • Export Citation
  • 27.

    RichardsonPGBarlogieBBerensonJ. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med2003;348:26092617.

  • 28.

    RichardsonPGSonneveldPSchusterMW. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol2009;144:895903.

    • Search Google Scholar
    • Export Citation
  • 29.

    RichardsonPGSonneveldPSchusterMW. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med2005;352:24872498.

    • Search Google Scholar
    • Export Citation
  • 30.

    El-CheikhJStoppaAMBouabdallahR. Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma. Clin Lymphoma Myeloma2008;8:146152.

    • Search Google Scholar
    • Export Citation
  • 31.

    CaravitaTPetrucciMTSpagnoliA. Neuropathy in multiple myeloma patients treated with bortezomib: a multicenter experience [abstract]. Presented at the 2007 American Society of Hematology Annual Meeting; December 8–11 2007; Atlanta Georgia. Abstract 4823.

    • Search Google Scholar
    • Export Citation
  • 32.

    SilvermanLCsizmadiaVBrewerK. Proteasome inhibitor associated neuropathy is mechanism based [abstract]. Annual Meeting of the American Society of Hematology. 2008. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 2646.

    • Search Google Scholar
    • Export Citation
  • 33.

    KirkCJJiangJMuchamuelT. The selective proteasome inhibitor carfilzomib is well tolerated in experimental animals with dose intensive administration [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 2765.

    • Search Google Scholar
    • Export Citation
  • 34.

    JagannathSVijRStewartAK. The Multiple Myeloma Research Consortium (MMRC). Initial results of PX-171-003, an open-label, single-arm, phase II study of carfilzomib (CFZ) in patients with relapsed and refractory multiple myeloma (MM) [abstract]. Blood2008;112:Abstract 864.

    • Search Google Scholar
    • Export Citation
  • 35.

    JagannathSBarlogieBBerensonJ. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol2004;127:165172.

    • Search Google Scholar
    • Export Citation
  • 36.

    RichardsonPGHideshimaTMitsiadesCAndersonK. Proteasome inhibition in hematologic malignancies. Ann Med2004;36:304314.

  • 37.

    DhawanRDelforgeMDe SamblanxH. Peripheral neuropathy as assessed in an international observational study of bortezomib [abstract]. Presented at the XII International Myeloma Workshop; February 26–March 1 2009; Washington D.C. Abstract 134.

    • Search Google Scholar
    • Export Citation
  • 38.

    San MiguelJFSchlagRKhuagevaNK. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med2008;359:906917.

    • Search Google Scholar
    • Export Citation
  • 39.

    ColsonKDossDSSwiftRTarimanJ. Expanding role of bortezomib in multiple myeloma: nursing implications. Cancer Nurs2008;31:239249.

  • 40.

    SmithGG. Proteasome inhibition in cancer therapy. J Infus Nurs2005;28:258264.

  • 41.

    DworkinRHO'ConnorABBackonjaM. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain2007;132:237251.

  • 42.

    JensenTSFinnerupNB. Management of neuropathic pain. Curr Opin Support Palliat Care2007;1:126131.

  • 43.

    ColvinLAJohnsonPRMitchellR. From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J Clin Oncol2008;26:45194520.

    • Search Google Scholar
    • Export Citation
  • 44.

    PerroneGHideshimaTIkedaT. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia2009;23:16791686

  • 45.

    ZinCSNissenLMSmithMT. An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy. CNS Drugs2008;22:417442.

    • Search Google Scholar
    • Export Citation
  • 46.

    WeberDMChenCNiesvizkyR. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med2007;357:21332142.

    • Search Google Scholar
    • Export Citation
  • 47.

    DimopoulosMSpencerAAttalM. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med2007;357:21232132.

    • Search Google Scholar
    • Export Citation
  • 48.

    JagannathSVijRStewartK. Final results of PX-171-003-A0 part 1 of an open-label single-arm phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8504.

    • Search Google Scholar
    • Export Citation
  • 49.

    HofmeisterCCRichardsonPZimmermanT. Clinical trial of the novel structure proteasome inhibitor NPI-0052 in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8505.

    • Search Google Scholar
    • Export Citation
  • 50.

    MitsiadesNMitsiadesCSPoulakiV. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood2002;99:45254530.

    • Search Google Scholar
    • Export Citation
  • 51.

    WangMGiraltSDelasalleK. Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple myeloma. Hematology2007;12:235239.

    • Search Google Scholar
    • Export Citation
  • 52.

    ZangariMBarlogieBBurnsMJ. Velcade-thalidomide-dexamethasone for advance and refractory multiple myeloma: long-term follow-up of phase I-II trial UARK 2001-37: superior outcome in patients with normal cytogenetics and no prior thalidomide [abstract]. Presented at the 2005 American Society of Hematology Annual Meeting; December 10–13 2005; Atlanta Georgia. Abstract 2552.

    • Search Google Scholar
    • Export Citation
  • 53.

    RichardsonPLonialSJakubowiakA. Lenalidomide bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma: encouraging efficacy in high risk groups with updated results of a phase I/II study [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 92.

    • Search Google Scholar
    • Export Citation
  • 54.

    RichardsonPJagannathSJakubowiakA. Lenalidomide bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma: encouraging response rates and tolerability with correlation of outcome and adverse cytogenetics in a phase II study [abstract]. Presented at the 2008 American Society of Hematology Annual Meeting; December 6–9 2008; San Francisco California. Abstract 1742.

    • Search Google Scholar
    • Export Citation
  • 55.

    RichardsonPGChanan-KhanALonialS. Tanespimycin plus bortezomib in patients with relapsed and refractory multiple myeloma: final results of a phase I/II study [abstract]. Presented at the 2009 American Society of Clinical Oncology Annual Meeting; May 29–June 2 2009; Orlando Florida. Abstract 8503.

    • Search Google Scholar
    • Export Citation
  • 56.

    BergerAMAbernethyAPAtkinsonA. NCCN clinical practice guidelines in oncology: cancer-related fatigue version 1.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Accessed May 12 2009.

    • Search Google Scholar
    • Export Citation
  • 57.

    MorrowGRShelkeARRoscoeJA. Management of cancer-related fatigue. Cancer Invest2005;23:229239.

  • 58.

    StasiRAbrianiLBeccagliaP. Cancer-related fatigue: evolving concepts in evaluation and treatment. Cancer2003;98:17861801.

  • 59.

    CurtGABreitbartWCellaD. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist2000;5:353360.

    • Search Google Scholar
    • Export Citation
  • 60.

    MorrowGR. Cancer-related fatigue: causes, consequences, and management. Oncologist2007;12(Suppl 1):13.

  • 61.

    HofmanMRyanJLFigueroa-MoseleyCD. Cancer-related fatigue: the scale of the problem. Oncologist2007;12(Suppl 1):410.

  • 62.

    VogelzangNJBreitbartWCellaD. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. Semin Hematol1997;34(3 Suppl 2):412.

    • Search Google Scholar
    • Export Citation
  • 63.

    OrlowskiRZNaglerASonneveldP. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol2007;25:38923901.

    • Search Google Scholar
    • Export Citation
  • 64.

    RajkumarSVJacobusSCallanderN. A randomized trial of lenalidomide plus high-dose dexamethasone vs lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. Presented at the 2007 American Society of Hematology Annual Meeting; December 8–11 2007; Atlanta Georgia. Abstract 74.

    • Search Google Scholar
    • Export Citation
  • 65.

    BreitbartWAlici-EvcimenY. Update on psychotropic medications for cancer-related fatigue. J Natl Compr Canc Netw2007;5:10811091.

  • 66.

    BreitbartWAliciY. Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. Clin J Oncol Nurs2008;12(5 Suppl):2736.

    • Search Google Scholar
    • Export Citation
  • 67.

    LaubachJPMitsiadesCSMahindraA. Novel therapies in the treatment of multiple myeloma. J Natl Compr Cancer Netw2009;7:947960.

  • 68.

    RichardsonPGMitsiadesCSchlossmanR. New drugs for myeloma. Oncologist2007;12:664689.

Article Information

Cited By

PubMed

Google Scholar

Related Articles

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 176 176 11
PDF Downloads 23 23 5
EPUB Downloads 0 0 0