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The following module was designed to supplement medical students’ learning in the clinic. Please take the time to read through each module by clicking the headings below. Information on how to diagnose and manage common chronic complications of cancer treatment, and appropriate follow-up plans for patients after curative cancer treatment is provided.

Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared adverse effects of chemotherapy feared by patients [1]. CINV can be prevented in up to 70 to 80% of patients [1,4]. Therefore, it is important for all clinicians to understand and manage CINV.


Adapted from the National Comprehensive Cancer Network Clinical Practice Guidelines for Neuroendocrine and Adrenal Tumors [5]

Risk Factors

  1. Emetogenicity of chemotherapy agent
  2. Female sex
  3. Patient age less than 55
  4. History of previous CINV
  5. Anxiety or depression
  6. History of alcohol or recreational drug use [3, 4]


As alluded to earlier, the overarching principle of management of CINV is to prevent the nausea and vomiting from developing in the first place. Antiemetic prophylaxis should be administered anytime where the risk of CINV is > 10% [3]. The risk is determined by the emetogenicity of the chemotherapy agent, as well as several patient factors, such as the ones listed above [2,3]. When delivering radiation to the abdomen or pelvis one may also consider prophylactically giving medications to prevent nausea or vomiting [3].

Non-pharmacologic management

It is important to maintain hydration and nutrition [4]. This can be done by eating small meals staggered throughout the day [4]. It may also help to have patients only eat a light meal prior to treatment [4]. Encourage the patient to drink lots of fluids. Cool beverages sipped on throughout the day may help [4]. There are some studies that have shown that ginger may reduce nausea [4].

Pharmacologic management

Serotonin (5-HT3) Receptor Antagonists

The 5-HT3 receptor antagonists are the main drug class used for CINV, as they have the highest therapeutic index for the prevention of CINV [3, 4]. The main prototype for this class is ondansetron. In fact, it has been shown that a single dose of ondansetron prior to the administration of chemotherapy is equivalent to a multiple-dose regimen of ndansetron after the development of nausea and vomiting [26]. One of the largest adverse effects to be aware of for ondansetron is QT prolongation. Generally, this QT prolongation is quite small, and will return to baseline approximately 24 hours after administration [4]. However, if the patient already has a risk of prolonged QT syndrome, whether its genetic or due to other drugs, the clinician must use caution in administrating the 5-HT3 antagonists [4].

Neurokinin-1 Receptor (NK1R) Antagonists

The neurokinin-1 receptor (NK1R) antagonists are also highly effective agents in the prevention of chemotherapy-induced nausea and vomiting [3]. These are especially indicated when the patient is receiving the chemotherapy through IV and it is highly emetogenic [4]. The main prototype for this drug class is Aprepitant. So far, it is only available for oral use. Although NK1R antagonists have not been directly compared to other antiemetics for CINV, the evidence suggests that the NK1R antagonists are similar in efficacy to the 5-HT3 antagonists for CINV [3].


Glucocorticoids, given in short doses and intervals, are also highly used in CINV [3, 4]. Generally, dexamethasone is the agent of choice. Dexamethasone is primarily given in combination with either a 5-HT3 receptor antagonist or a NK1R antagonist. On their own, glucocorticoids alone are insufficient to control CINV [4].


Olanzapine is a new addition to the arsenal of drugs recognized for use of CINV. Olanzapine is a second-generation antipsychotic is very useful in the prevention of CINV [3, 4].


Many patients experience diarrhea while undergoing chemotherapy treatment. Both chemotherapy and radiotherapy are possible etiologies for diarrhea in a cancer patient. Chemotherapy-induced diarrhea (CID) can occur in up to 50-80% of patients receiving chemotherapy, depending on the regimen [6].

It is important for health practitioners to know how to recognize and manage this, as it can lead to severe complications [6, 7]. CID can be debilitating, and in some cases, even be life-threatening [6]. CID can cause malnutrition and depletion of fluids and electrolytes [6]. Thus, it can lead to hospitalization, renal and cardiovascular compromise, and death [6, 8].


First, it is important to rule out other causes of diarrhea, such as infectious causes and ischemic colitis [31]. Management of chemotherapy-induced diarrhea begins with assessment of the patient to rule out significant volume depletion or other comorbidities that may require hospitalization [6].

Non-pharmacologic management

Mild diarrhea can be managed with dietary changes [7, 8]. This includes the avoidance of foods and beverages that can make diarrhea worse, such as milk, coffee, alcohol, fried/greasy foods, and spicy foods [7, 8]. A BRAT diet (bananas, rice, applesauce, and toast) may be helpful, as these are easily digested foods [7, 8]. It is also important to increase the consumption of clear fluids to replace any volume losses that may have occurred.

Pharmacologic management


Loperamide is a synthetic opioid that functions by decreasing intestinal motility by inhibiting peristalsis of the smooth muscle [7]. This slows transit time, and allows for more absorption of water from the GI lumen [8]. Unlike other opioids, it has no systemic effects due to its limited absorption [7].

Loperamide is a good first-line agent for mild to moderate (grade 1 or 2) CID [7]. The standard dose of loperamide is 4 mg followed by 2 mg every four hours or after each unformed stool, with a maximum dose being 16 mg/day [7]. A more aggressive regimen (4 mg followed by 2 mg every two hours) is also recommended at the onset of diarrhea with a chemotherapy regimen that includes high-dose irinotecan [7].


Octreotide is a synthetic somatostatin analog, which acts via several mechanisms [7]. It decreases the secretion of several GI hormones (such as VIP, serotonin, and gastrin), prolongs GI transit time, and increased absorption of fluid and electrolytes [7]. For loperamide-refractory diarrhea, octreotide subcutaneously can be administered [30]. The recommended dose is 100-150 mcg subcutaneously, three times per day [8]. The duration of treatment should be individualized, and can be discontinued 24 hours after the end of the diarrhea [8].

Radiation Dermatitis and Fibrosis

Radiation therapy is an integral component of cancer treatment, which uses high energy rays to kill cancer cells and shrink tumors. As a side effect of this, nearby healthy cells, such as the skin, can be damaged as a result, leading to radiation dermatitis. This is a skin condition that is very common to patients receiving radiation therapy, occurring in up to 95% of cases [9].

Fibrosis can occur in any tissue exposed to radiation, with the initial presentation of symptoms typically occurring within 4 to 12 months after treatment. The degree of fibrosis varies based on several factors including the total dose, the volume of tissue treated and the fractionation schedule, as well as other important but less contributory factors like other concurrent or previous therapies, presence of comorbidities such as diabetes mellitus and genetic susceptibility [10, 11].  


In radiation-induced dermatitis and fibrosis, the radiated tissue undergoes a process similar to any process of inflammation and wound healing [10]. Increased inflammatory infiltrates, increased extracellular matrix protein and collagen deposition, and abnormal vascular changes all contribute to the fibrotic transformation that occurs gradually and continues over several months to years after the exposure.

Risk Factors

  1. Obesity
  2. Advanced age
  3. Female sex
  4. Chronic sun exposure
  5. Total dose of radiation
  6. Fractionation schedule
  7. Surface area exposed to radiation
  8. Connective tissue diseases

Classification of Radiation Dermatitis

Grading of radiation dermatitis [9, 12].

Clinical Manifestations of Fibrosis

Most common clinical manifestations of radiation-induced fibrosis by body site (10)

Prevention and Management

The best way to manage radiation dermatitis and fibrosis is to prevent its occurrence. This is especially important for patients who have risk factors [12 ,13]. New radiation delivery techniques are limiting exposure to surrounding tissues and have become much more targeted, which has helped reduce the area of fibrosis post-treatment [11]. In addition, the following preventative measures are helpful:

General protective measures:
o Wearing loose-fitting clothes [12, 13].
o Washing skin with lukewarm water with mild soaps [12, 13].
o Using unscented, lanolin-free, water-based moisturizers [13]. These should be avoided immediately before treatment, as they can alter the effective radiation dose.

Topical corticosteroids:
o Low to medium potency topical corticosteroid used once to twice daily after each radiation treatment session [14]. Results in slower progression to acute radiation dermatitis and helpsdecrease severity of symptoms [14, 15]

Pentoxifylline (often in combination with vitamin E) has been shown to have some benefit for prevention as well as treatment of fibrosis [10, 16].  This drug inhibits platelet aggregation, increases microvascular blood flow and may inhibit fibroblast proliferation thereby reducing production of extracellular matrix [10]  In practice, pentoxifylline is not that commonly used, but can be a potential consideration.  While there are some cell-based therapies in clinical trials that target the molecular mechanisms of the inflammatory pathway that result in fibrosis, current treatment options are generally supportive and are aimed at addressing symptoms [17].

Below are general guidelines on the management of radiation dermatitis.

Management of radiation dermatitis by grade [9, 12, 18].

In addition to the above, physiotherapy, along with a regular exercise routine, can help increase range of motion, improve muscle strength and lessen progressive muscle atrophy [17]. Massage therapy, including fascial techniques and myofascial relaxation, can improve blood flow, reduce lymphedema and help to loosen tense soft tissue [17].

Virtual Patient Case

Use your mouse to click through the slides and answer each question in the text box provided.
Note: This case can be completed on an iPad. To do this download the (free) Articulate Mobile Player for the iPad by clicking here.


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  2. Hesketh PJ. UpToDate: Pathophysiology and prediction of chemotherapy-induced nausea and vomiting. 2017. Available at: http://www.uptodate.com. Accessed March 24 2019.
  3. Hesketh PJ. UpToDate: Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. 2018. Available at: http://www.uptodate.com. Accessed March 24 2019.
  4. Natale, JJ. Overview of the prevention and management of CINV. Am J Manag Care. 2018; 24-S0.
  5. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed July 22, 2018.
  6. Stein, A., Voigt, W., & Jordan, K. (2010). Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Therapeutic advances in medical oncology, 2(1), 51–63.
  7. Gibson R.J., Stringer A.M. (2009) Chemotherapy-induced diarrhoea. Curr Opin Support Palliat Care 3: 31–35
  8. Krishnamurthi SS, Macaron C. UpToDate: Management of acute chemotherapy-related diarrhea. 2017. Available at: http://www.uptodate.com. Accessed March 24 2019.
  9. Hymes SR, Strom EA, Fife C. Radiation dermatitis: Clinical presentation, pathophysiology and treatment 2006. J Am Acad Dermatol 2006; 54:28-46.
  10. Weiss E. Clinical manifestations, prevention, and treatment of radiation-induced fibrosis - UpToDate [Internet]. 2019 [cited 2019 May 15]. Available from: https://www.uptodate.com/contents/clinical-manifestations-prevention-and-treatment-of-radiation-induced-fibrosis
  11. Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy HHS Public Access. J Cancer Res Clin Oncol [Internet]. 2015 [cited 2019 May 15];141(11):1985–94. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573901/pdf/nihms713339.pdf
  12. Bray, F. N., Simmons, B. J., Wolfson, A. H., & Nouri, K. (2016). Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. Dermatology and therapy, 6(2), 185–206.
  13. Wolf JR. UpToDate: Radiation dermatitis. 2018. Available at: http://www.uptodate.com. Accessed March 24 2019.
  14. Mehrara B. Clinical features and diagnosis of peripheral lymphedema - UpToDate [Internet]. 2019 [cited 2019 May 14]. Available from: https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-peripheral-lymphedema?topicRef=882&source=see_link
  15. Lymphedema [Internet]. [cited 2019 May 14]. Available from: http://www.bccancer.bc.ca/health-info/types-of-cancer/breast-cancer/lymphedema
  16. Okunieff P, Augustine E, Hicks JE, Cornelison TL, Altemus RM, Naydich BG, et al. Pentoxifylline in the Treatment of Radiation-Induced Fibrosis. J Clin Oncol [Internet]. 2019 [cited 2019 May 16];22:2207–13. Available from: www.jco.org
  17. Hojan K, Milecki P. Opportunities for rehabilitation of patients with radiation fibrosis syndrome. 2014 [cited 2019 May 15]; Available from: www.sciencedirect.com
  18. Schmuth M, Wimmer MA, Hofer S, et al. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study. Br J Dermatol. 2002;146(6):983–99.

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