Clinical assessment of CIPN should include patient history, a detailed description of symptoms, and clinical measures of nerve function. Preexisting medical conditions such as diabetes, alcoholic neuropathy, or Charcot Marie Tooth disease will increase the likelihood of significant neuropathy.50,54 Questioning patients about symptoms of CIPN is an important component of the evaluation because CIPN symptoms are often underreported. Hence, clinicians must rely on active questioning rather than patient-volunteered information.38,55,56 Physical assessment should include examination of light touch and vibration thresholds, pin-prick sensitivity, distal muscle strength, and deep tendon reflexes. Tools, such as the clinical version of the Total Neuropathy Scale and the modified Total Neuropathy Scale exist that compile these individual findings into a composite score.57,58 Since neuropathic pain is not a major component of these scales, using a specific self-reported measure of this disabling symptom such as the Neuropathic Pain Scale or the Leeds Assessment of Neuropathy Symptoms and Signs may be warranted.59 A combination of the above-mentioned tools can assist the practitioner in both assembling the appropriate set of clinical assessments and monitoring for changes in nerve function over time.
Determining the contribution of CIPN to activity limitations and participation restrictions is an important part of the screening of these patients. Balance deficits and gait abnormalities have been reported in patients with CIPN, placing this population at greater risk of falls.58 The Berg Balance test, the Tinetti, and simple fall assessment tools may be used to document these restrictions.60,61 In addition, decreased hand function may limit participation in activities of daily living such as handwriting, dressing, and grooming, making both the screening for such deficits and referring to occupational therapy vitally important.51
Possible treatments for CIPN are diverse and, unfortunately, there is no conclusive evidence that available medical treatments are helpful in preventing CIPN or effective in treating persistent CIPN.62 Likewise, there is no conclusive evidence that physical therapy interventions can prevent or reverse peripheral nerve impairments due to CIPN. However, descriptive studies suggest that aerobic exercise or laser therapy may help those with peripheral neuropathy from diabetes and carpal tunnel compression.63–65 Other treatment possibilities include addressing balance and gait restrictions; an integrative balance-retraining program; patient education in how to manage neuropathic pain symptoms, allodynia, and hyperalgesia; and fine motor retraining of the hand.50,66
Treatment interventions for persistent or worsening CIPN are generally tailored toward limiting activity limitations caused by gait and balance impairments. Improvement in distal muscle strength and range can often assist in improving gait abnormalities, but assistive devices and orthotics may be necessary. Balance training and teaching protective household adaptations are indicated to reduce the risk of falls in this population.50
Extravasation of infused chemotherapeutic agents can occur when the needle punctures the vein. Older patients are at particular risk because of their brittle veins. Immediate effects include local inflammation, pain, tightness at the site of the injection; phlebitis in the infused vein (vesicants), and necrosis (vesicants) of the surrounding tissue. Long-term effects can include skin damage and scarring of the epidermis and underlying tissue. The use of a Power Port or Hickman line allows long-term access to larger veins, thus reducing peripheral vein stress and risk for extravasation. Irritants may induce local sclerosis or hyperpigmentation. Vesicants may induce tissue necrosis with severe acute and often long-term injury.70,75
Hyperpigmentation and discoloration of the skin, mucous membranes, nails, or hair may occur with chemotherapy administration and are likely the result of toxic effects of the chemotherapy agent on melanocytes. Nail changes also include ridging of and premature separation of the nail plate.70,76 Changes may be acute or permanent.68,70,71
Radiation recall reaction is an adverse skin reaction (inflammation) that occurs at a site of previous radiation exposure (months to years before) and in response to recent chemotherapy therapy. Recall reactions also occur at sites of previous chemotherapy extravasation or at previously used infusion sites.69,77,78
Adverse effects of cancer and/or its treatment can last long after a cure has been achieved and treatment has ended or may only emerge long after treatment has ended. In either case, these late effects have the potential for complicating a patient's clinical picture, making it necessary for a treating PT to clearly understand both the patient's cancer history and the current ramifications of past cancer treatments. Using appropriate, valid, and reliable screening tools will allow the PT to quickly rule in or out late effects of cancer and chemotherapy, thus allowing for optimal treatment intervention from a multidisciplinary approach. This brief monograph has attempted to identify chemotherapy-specific late effects and methods of screening for those effects. Our hope is that this information will enhance PT services provided to this complex patient population.
1. Balis FM, Holcenberg JS, Blaney SM. General principles of chemotherapy
. In: Pizzo PA, Poplack DG eds. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia, PA: Lippincott-Raven; 2002:237.
2. Kaste SC, Metzger ML, Minhas A, et al. Pediatric Hodgkin lymphoma survivors at negligible risk for significant bone mineral density deficits. Pediatr Blood Cancer. 2009;52(4):516–521.
3. Majhail NS, Flowers ME, Ness KK, et al. High prevalence of metabolic syndrome after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2009;43(1):49–54.
4. Meacham LR, Chow EJ, Ness KK, et al. Cardiovascular risk factors in adult survivors of pediatric cancer'a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 2010;19(1):170–181.
5. Nathan PC, Ford JS, Henderson TO, et al. Health behaviors, medical care, and interventions to promote healthy living in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2009;27(14):2363–2373.
6. Ness KK, Hudson MM, Ginsberg JP, et al. Physical performance limitations in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2009;27(14):2382–2389.
7. Ness KK, Leisenring WM, Huang S, et al. Predictors of inactive lifestyle among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2009;115(9):1984–1994.
8. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for primary prevention of cardiovascular disease and stroke: 2002 update'consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002;106(3):388–391.
9. National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) version 4.0. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicology Criteria (CTC) Web site. http://ctep.info.nih.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40
. Published May 28, 2009. Updated 2010. Accessed October 20, 2010.
11. Ness KK, Leisenring WM, Huang S, et al. Predictors of inactive lifestyle among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2009;115(9):1984–1994.
12. Marchese VG, Chiarello LA, Lange BJ. Effects of physical therapy
intervention for children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2004;42(2):127–133.
13. Marchese VG, Connolly BH, Able C, et al. Relationships among severity of osteonecrosis, pain, range of motion, and functional mobility in children, adolescents, and young adults with acute lymphoblastic leukemia. Phys Ther. 2008;88(3):341–350.
14. Marchese VG, Rai SN, Carlson CA, et al. Assessing functional mobility in survivors of lower-extremity sarcoma: reliability and validity of a new assessment tool. Pediatr Blood Cancer. 2007;49(2):183–189.
15. Marchese VG, Spearing E, Callaway L, et al. Relationships among range of motion, functional mobility, and quality of life in children and adolescents after limb-sparing surgery for lower-extremity sarcoma. Pediatr Phys Ther. 2006;18(4):238–244.
16. Laack SJ PA. Respiratory and cardiovascular drug actions. In: Frownfelter DL, Dean E eds. Cardiovascular and Pulmonary Physical Therapy
. 4th ed. St. Louis, MO: Mosby/Elsevier; 2006:848.
17. Huber GM. Special tests. In: Frownfelter DL, Dean E eds. Cardiovascular and Pulmonary Physical Therapy
: Evidence and Practice. 4th ed. St. Louis, MO: Mosby/Elsevier; 2006:848.
18. Scherer SA, Noteboom JT, Flynn TW. Cardiovascular assessment in the orthopaedic practice setting. J Orthop Sports Phys Ther. 2005;35(11):730–737.
19. Balady GJ, Chaitman B, Driscoll D, et al. Recommendations for cardiovascular screening, staffing, and emergency policies at health/fitness facilities. Circulation. 1998;97(22):2283–2293.
20. Thompson WR, Gordon NF, Pescatello LS, American College of Sports Medicine. ACSM's Guidelines for Exercise Testing and Prescription. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:380.
21. Fogelman I, Blake GM, Blamey R, et al. Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporos Int. 2003;14(12):1001–1006.
22. Hijiya N, Ness KK, Ribeiro RC, Hudson MM. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer. 2009;115(1):23–35.
23. Spanik S, Spanikova B. Bone mineral density in early breast cancer patients. Bratisl Lek Listy. 2010;111(1):27–32.
24. Ghazi M, Roux C. Hormonal deprivation therapy-induced osteoporosis in postmenopausal women with breast cancer. Best Pract Res Clin Rheumatol. 2009;23(6):805–811.
25. Alibhai SM, Duong-Hua M, Cheung AM, et al. Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men. J Urol. 2010;184(3):918–923.
26. Shim K, MacKenzie MJ, Winquist E. Chemotherapy
-associated osteonecrosis in cancer patients with solid tumours: a systematic review. Drug Saf. 2008;31(5):359–371.
27. Salaffi F, Silveri F, Stancati A, Grassi W. Development and validation of the osteoporosis prescreening risk assessment (OPERA) tool to facilitate identification of women likely to have low bone density. Clin Rheumatol. 2005;24(3):203–211.
28. Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25(25):3877–3883.
29. Dixon D, Johnston M, McQueen M, Court-Brown C. The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) can measure the impairment, activity limitations and participation restriction constructs from the International Classification of Functioning, Disability and Health (ICF). BMC Musculoskelet Disord. 2008;9:114.
30. Hawker G, Melfi C, Paul J, Green R, Bombardier C. Comparison of a generic (SF-36) and a disease specific (WOMAC) (Western Ontario and McMaster Universities Osteoarthritis Index) instrument in the measurement of outcomes after knee replacement surgery. J Rheumatol. 1995;22(6):1193–1196.
31. Demark-Wahnefried W, Aziz NM, Rowland JH, Pinto BM. Riding the crest of the teachable moment: promoting long-term health after the diagnosis of cancer. J Clin Oncol. 2005;23(24):5814–5830.
32. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15(6):556–565.
33. Irwin ML, Ainsworth BE. Physical activity interventions following cancer diagnosis: methodologic challenges to delivery and assessment. Cancer Invest. 2004;22(1):30–50.
34. O'Connell BO, Baker L, Gaskin CJ, Hawkins MT. Risk items associated with patient falls in oncology and medical settings. J Nurs Care Qual. 2007;22(2):130–137.
35. Syrjala KL, Langer SL, Abrams JR, Storer BE, Martin PJ. Late effects of hematopoietic cell transplantation among 10-year adult survivors compared with case-matched controls. J Clin Oncol. 2005;23(27):6596–6606.
36. Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005;104(9):1998–2005.
37. Gralow JR, Biermann JS, Farooki A, et al. NCCN task force report: bone health in cancer care. J Natl Compr Canc Netw. 2009;7 (suppl 3):S1–S32; quiz S33-S35.
38. Jensen MP, Chang HY, Lai YH, Syrjala KL, Fann JR, Gralow JR. Pain in long-term breast cancer survivors: frequency, severity, and impact. Pain Med. 2010;11(7):1099–1106.
39. King NA, Caudwell P, Hopkins M, et al. Metabolic and behavioral compensatory responses to exercise interventions: barriers to weight loss. Silver Spring. 2007;15(6):1373–1383.
40. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy
: a multicenter randomized controlled trial. J Clin Oncol. 2007;25(28):4396–4404.
41. Galantino ML, Cannon N, Hoelker T, Quinn L, Greene L. Effects on Iyengar yoga on measures of cognition, fatigue, quality of life, flexibility, and balance in breast cancer survivors: a case series. Rehabil Oncol. 2008;26(1):18–27.
42. Freeman JR, Broshek DK. Assessing cognitive dysfunction in breast cancer: what are the tools? Clin Breast Cancer. 2002;3(suppl 3):S91–99.
43. Paganini-Hill A, Clark LJ. Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2000;64(2):165–176.
44. Ahles TA, Saykin AJ. Breast cancer chemotherapy
-related cognitive dysfunction. Clin Breast Cancer. 2002;3(suppl 3):S84–90.
45. Ahles TA, Saykin AJ, Furstenberg CT, et al. Neuropsychologic impact of standard-dose systemic chemotherapy
in long-term survivors of breast cancer and lymphoma. J Clin Oncol. 2002;20(2):485–493.
46. Hurria A, Goldfarb S, Rosen C, et al. Effect of adjuvant breast cancer chemotherapy
on cognitive function from the older patient's perspective. Breast Cancer Res Treat. 2006;98(3):343–348.
47. Vardy J, Rourke S, Tannock IF. Evaluation of cognitive function associated with chemotherapy
: a review of published studies and recommendations for future research. J Clin Oncol. 2007;25(17):2455–2463.
48. Vardy J, Wong K, Yi QL, et al. Assessing cognitive function in cancer patients. Support Care Cancer. 2006;14(11):1111–1118.
49. Galantino ML, Brown DC, Stricker CT, Farrar JT. Development and testing of a cancer cognition questionnaire. Rehabil Oncol. 2006;24(2):15–22.
50. Stubblefield MD, Burstein HJ, Burton AW, et al. NCCN task force report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7(suppl 5):S1–S26; quiz S27-S28.
51. Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004;109(1/2):132–142.
52. Ramchandren S, Leonard M, Mody RJ, et al. Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. J Peripher Nerv Syst. 2009;14(3):184–189.
53. Siegal T, Haim N. Cisplatin-induced peripheral neuropathy. Frequent off-therapy deterioration, demyelinating syndromes, and muscle cramps. Cancer. 1990;66(6):1117–1123.
54. Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy
: clinical and electrophysiological studies. Ann Neurol. 1994;35(3):304–311.
55. Basch E, Iasonos A, McDonough T, et al. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006;7(11):903–909.
56. Markman M. Chemotherapy
-induced peripheral neuropathy: underreported and underappreciated. Curr Pain Headache Rep. 2006;10(4):275–278.
57. Cavaletti G, Jann S, Pace A, et al. Multi-center assessment of the Total Neuropathy Score for chemotherapy
-induced peripheral neurotoxicity. J Peripher Nerv Syst. 2006;11(2):135–141.
58. Wampler MA, Topp KS, Miaskowski C, Byl NN, Rugo HS, Hamel K. Quantitative and clinical description of postural instability in women with breast cancer treated with taxane chemotherapy
. Arch Phys Med Rehabil. 2007;88(8):1002–1008.
59. Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology. 1997;48(2):332–338.
60. Berg KO, Maki BE, Williams JI, Holliday PJ, Wood-Dauphinee SL. Clinical and laboratory measures of postural balance in an elderly population. Arch Phys Med Rehabil. 1992;73(11):1073–1080.
61. Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc. 1986;34(2):119–126.
62. Gutiérrez-Gutiérrez G, Sereno M, Miralles A, Casado-Sáenz E, Gutiérrez-Rivas E. Chemotherapy
-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies. Clin Transl Oncol. 2010;12(2):81–91.
63. Balducci S, Iacobellis G, Parisi L, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications. 2006;20(4):216–223.
64. Nathan PA. Effects of an aerobic exercise program on median nerve conduction and symptoms associated with carpal tunnel syndrome. J Occup Environ Med. 2002;44(4):303–304.
65. Leonard DR, Farooqi MH, Myers S. Restoration of sensation, reduced pain, and improved balance in subjects with diabetic peripheral neuropathy: a double-blind, randomized, placebo-controlled study with monochromatic near-infrared treatment. Diabetes Care. 2004;27(1):168–172.
66. Wampler MA, Hamolsky D, Hamel K, Melisko M, Topp KS. Case report: painful peripheral neuropathy following treatment with docetaxel for breast cancer. Clin J Oncol Nurs. 2005;9(2):189–193.
67. Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol. 2002;14(2):212–216.
68. Heidary N, Naik H, Burgin S. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol. 2008;58(4):545–570.
69. Hood AF. Cutaneous side effects of cancer chemotherapy
. Med Clin North Am. 1986;70(1):187–209.
70. Sanborn RE, Sauer DA. Cutaneous reactions to chemotherapy
: commonly seen, less described, little understood. Dermatol Clin. 2008;26(1):103–119, ix.
71. Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy
. J Am Acad Dermatol. 1999;40(3):367–98; quiz 399–400.
72. Waltzer JF, Flowers FP. Bullous variant of chemotherapy
-induced acral erythema. Arch Dermatol. 1993;129(1):43–45.
73. Baack BR, Burgdorf WH. Chemotherapy
-induced acral erythema. J Am Acad Dermatol. 1991;24(3):457–461.
74. Demirçay Z, Gürbüz O, Alpdogan TB, et al. Chemotherapy
-induced acral erythema in leukemic patients: a report of 15 cases. Int J Dermatol. 1997;36(8):593–598.
75. Ener RA, Meglathery SB, Styler M. Extravasation of systemic hemato-oncological therapies. Ann Oncol. 2004;15(6):858–862.
76. Slee PH. Images in clinical medicine. Nail changes after chemotherapy
. N Engl J Med. 1997;337(3):168.
77. Smith KJ, Germain M, Skelton H. Histopathologic features seen with radiation recall or enhancement eruptions. J Cutan Med Surg. 2002;6(6):535–540.
78. Ee HL, Yosipovitch G. Photo recall phenomenon: an adverse reaction to taxanes. Dermatology. 2003;207(2):196–198.