Editors: Skeel, Roland T.
Title: Handbook of Cancer Chemotherapy, 7th Edition
Copyright 2007 Lippincott Williams & Wilkins
> Table of Contents > Section IV - Selected Aspects of Supportive Care of Patients with Cancer > Chapter 27 - Side Effects of Cancer Chemotherapy
Side Effects of Cancer Chemotherapy
Janelle M. Tipton
Systemic cancer chemotherapy agents play a valuable role in cancer treatment; however, there are undesirable effects both to normal replicating and quiescent cells. Rapidly dividing normal cells that are vulnerable to damage include cells of the bone marrow, hair follicles, and mucous membranes, and reproductive system. Other toxicities may occur that are unrelated to cell growth and are particular to individual agents. The side effects of cancer chemotherapy agents may be acute, self-limited, and mild or can be chronic, permanent, and potentially life threatening in nature. Many advances have been made in the last 10 to 15 years in the management of side effects of chemotherapy. Although much progress has been made, the management of side effects continues to be of utmost importance for the tolerability of therapy and effect on overall quality of life. The implementation of evidence-based interventions has received increased emphasis and is critical in making appropriate clinical decisions for the management of side effects.
I. Acute reactions
Extravasation is defined as the leakage or infiltration of drug into the subcutaneous tissues. Vesicant drugs that extravasate are capable of causing tissue necrosis or sloughing. Irritant drugs cause inflammation or pain at the site of extravasation. Common vesicant and irritant agents and potential antidotes are listed in Table 27.1.
Risk factors for peripheral extravasation include small, fragile veins, venipuncture technique, site of venipuncture, drug administration technique, presence of superior vena cava syndrome, peripheral neuropathy, limited vein selection due to lymph node dissection, and concurrent use of medications that may cause somnolence, altered-mental status, excessive movements, vomiting, and coughing.
Table 27.1. Common vesicant and irritant drugs and potential antidotes
The incidence of extravasation for vesicant chemotherapy is recorded as 1% to 6% in the literature for peripheral chemotherapy. Extravasation may also occur with central venous catheters. Potential causes for central venous catheter extravasation include backflow secondary to fibrin sheath or thrombosis in the central venous catheter, needle dislodgement from a venous access port, central venous catheter damage, breakage, or separation, and displacement or migration of the catheter from the vein.
Common signs and symptoms of extravasation are pain or burning at the IV site, redness, swelling, inability to obtain a blood return, and change in the quality of the infusion. Any of these complaints or observations should be considered a symptom of extravasation until proved otherwise.
Procedures to manage peripheral extravasation are imperative to have in place, including guidelines or orders for extravasation management of vesicant and irritant agents before administration. If an extravasation is suspected, the following actions should be taken:
Stop administration of the chemotherapy agent.
Leave the needle/catheter in place and immobilize the extremity.
Attempt to aspirate any residual drug in the tubing, needle, or suspected extravasation site.
Notify the physician.
Administer the appropriate antidote, as shown in Table 27.1. This may include instillation of a drug antidote or application of heat or cold to the site. Of note, hyaluronidase was not commercially available from2001 to late 2004. It is now available as Amphadase (hyaluronidase injection, Amphastar Pharmaceuticals, Rancho Cucamonga, CA).
Provide the patient and/or caregiver with instructions, including the need to elevate the site for 48 hours and the continuation of antidote measures as appropriate.
Discuss the need for further intervention with the physician, and photograph if indicated.
Document extravasation occurrence according to institutional guidelines.
Continued monitoring of extravasation site at 24 hours, 1 week, 2 weeks, and additionally as guideline recommends. Secondary complications such as infection and pain may occur. Follow-up photographs at these periods, if possible, are helpful in monitoring extent of injury and progress in healing.
Procedures for central extravasation are also critically important to follow, as extravasation of chemotherapeutic agents in the upper torso or neck area is difficult to manage and may result in extensive defects, requiring reconstructive surgery. Extreme caution should be taken by nurses administering chemotherapy by this route. Procedures followed in central extravasation are similar to peripheral extravasation. Assessment of lack of blood return, patient reports in changes of sensation, pain, burning, or
B. Hypersensitivity and anaphylaxis
Specific drugs with the potential for hypersensitivity with or without an anaphylactic response should be administered under constant supervision of a competent and experienced nurse and with a physician readily available, preferably during the daytime. Important preassessment data to be documented include the patient's allergy history, though this information may not predict an allergic reaction to chemotherapy. Other risk factors include previous exposure to the agent and failure to administer effective prophylactic medications. Drugs with the highest risk of immediate hypersensitivity reactions are asparaginase, murine monoclonal antibodies (e.g., ibritumomab tiuxetan), the taxanes (paclitaxel and docetaxel), and platinum compounds (cisplatin, carboplatin, oxaliplatin). Drugs with a low to moderate risk include the anthracyclines, bleomycin, IV melphalan, etoposide, and humanized (e.g., trastuzumab) or chimeric (e.g., rituximab) monoclonal antibodies. Test doses or skin tests may be performed if there is an increased suspicion for hypersensitivity. In specific occasions, this is generally done with carboplatin, bleomycin and asparaginase. A skin testing protocol for carboplatin skin testing is shown in Table 27.2.
Type 1 hypersensitivity reactions are the most common chemotherapy-induced type of reactions. These reactions characteristically occur within 1 hour of receiving the drug; however, with paclitaxel, the hypersensitivity reactions often occur within the first 10 minutes of the start of the infusion. Common manifestations of a type 1 reaction
Table 27.2. Sample carboplatin skin testing protocol
Retreatment and rechallenge of patients who have experienced paclitaxel-associated hypersensitivity reactions are supported in the literature. If rechallenge is considered, paclitaxel should be administered in the appropriate setting where immediate emergency situations may be handled. The decision to reinstitute paclitaxel should be based on the clinical importance of using the drug in
Table 27.3. Sample standing orders for hypersensitivity reactions to chemotherapy agents
Reinstitution of paclitaxel after experiencing a hypersensitivity reaction includes immediate discontinuation of the paclitaxel infusionat the onset of symptoms and rapid administration of additional diphenhydramine and methylprednisolone. Following stabilization of the patient and waiting approximately for 30 minutes, the paclitaxel infusion is reinitiated, with initial infusion rates of 10% to 25% of the total infusion rate. If tolerated, the rate can be gradually increased over the next several hours. Nursing care would also include vital signs every 5 minutes or continuous observation for the first 15 minutes, then every 15 minutes through the first hour, then hourly until the infusion is completed. An alternative is to pretreat the patient for 24 hours with dexamethasone 10 mg three times orally and to restart the infusion at the rate indicated earlier on the second day.
Desensitization approaches. Rechallenge after a severe hypersensitivity reaction of the second episode of hypersensitivity reaction to paclitaxel and carboplatin are documented in the literature; however, planning for the desensitization is necessary. Regimens including dexamethasone 20 mg orally at 36 and 12 hours before chemotherapy and on the morning of chemotherapy have been studied. A full 30minutes before the chemotherapy, other IV premedications such as dexamethasone 20 mg, diphenhydramine 50 mg, and H2-histamine antagonist are given. For paclitaxel, the desensitization procedure continues with the administration of a test dose of 2 mg in 100 mL of normal saline over 30 minutes. If there is no reaction, 10 mg in 100 mL of normal saline is given over 30 minutes, followed by the remaining full dose in 500 mL of normal saline over 3 hours if still no reaction. If a reaction is experienced, the usual diphenhydramine and methylprednisolone medications are given.
II. Nausea and vomiting
Patients who are about to begin chemotherapy are often concerned and apprehensive about nausea and vomiting. Nausea and vomiting can be distressing enough to the patient to cause extreme physiologic and psychological discomfort, culminating in withdrawal from therapy. With the advent of more effective antiemetic regimens in the last 15 years, many improvements in the prevention and control of nausea and vomiting have led to a better quality of life for patients receiving chemotherapy. The goal of therapy is to prevent the three phases of nausea and vomiting: that which occurs before treatment is administered (anticipatory), that which follows within the first 24 hours after treatment (acute), and that which occurs more than 24 hours after treatment (delayed). It is also important to assess nausea and vomiting separately because they are different events and may have different causes. Factors related to the chemotherapy that can affect the likelihood and severity of symptoms include the specific agents used, the doses of the drugs, and the schedule and route of administration. Other
A. Emetic potential of the drug
To plan an effective approach to control nausea and vomiting, the chemotherapeutic agents are grouped according to their emetic potential (Table 27.4). This type of categorization is helpful in making decisions regarding possible antiemetics to be used and how aggressive the antiemetic regimen should be for patients receiving chemotherapy for the first time or in subsequent treatments. It is important to select appropriate antiemetics from the various antiemetic classes, and not to under treat the patient for nausea and vomiting in the initial chemotherapy cycle. Failure to control nausea and/or vomiting may result in a conditioned response and subsequent anticipatory nausea and vomiting.
B. Antiemetic drugs
Agents that have been effective in preventing and treating nausea and vomiting (Table 27.5) come from various pharmacologic classes. They work by different mechanisms that may relate to the pathophysiologic processes causing nausea and vomiting. For many years, the mainstays of antiemetic therapy have been agents that block dopamine receptors. These agents have been somewhat effective but have limited value for highly emetogenic agents and, in escalating doses, have caused problematic side effects. Within the last 15 years, it was discovered that agents that block predominately the serotonin (5-hydroxytryptamine) subtype 3 (5-HT3) receptors, rather than the dopamine receptors, have greater efficacy in the prevention of nausea and vomiting. More recent research indicates that the tachykinins, including a peptide called substance P, play an important role in emesis. Substance P binds to the neurokinin type 1 (NK-1) receptor. Thus, the NK-1-receptor antagonists are now validated in their role in inhibiting nausea and vomiting with moderately and highly emetogenic chemotherapy. OralNK-1-receptor antagonists are thought to improve acute nausea and vomiting associated with chemotherapy when combined with standard regimens (i.e., dexamethasone and 5-HT3 receptor antagonists) and to have additional effect during the period of delayed nausea and vomiting, alone or in combination with dexamethasone.
C. Combination antiemetic therapy
Several antiemetic regimens are effective, but their design should be based on two general principles:
Combinations of antiemetics are more effective than single agents. It is common to use two or more antiemetics to prevent or manage nausea and vomiting.
Preemptive treatment and scheduled administration are more effective than reactive therapy to prevent nausea and vomiting early in therapy and to manage potential delayed nausea and vomiting in the days following treatment.
Table 27.6 shows examples of antiemetic regimens that may be used when the chemotherapy has a high, moderate, and low emetic potential.
D. Nonpharmacologic interventions
Patients who are likely to experience or who have experienced anticipatory
Table 27.4. Emetogenic potential for commonly used chemotherapeutic agentsa
Table 27.5. Agents used for chemotherapy-induced nausea and vomiting
Table 27.6. Examples of antiemetic regimens for prevention and management of chemotherapy-induced nausea and vomiting
E. Herbal remedies: ginger
There have long been anecdotally based recommendations for the use of ginger to help prevent and minimize chemotherapy-induced nausea and vomiting. Few randomized controlled trials have been done to evaluate ginger as an intervention in this patient population. Although early studies show safety and little toxicity, it is difficult to recommend the use of ginger because of the lack of evidence, particularly with respect to dosages and schedules.
III. Other short-term complications related to cancer chemotherapy
A. Stomatitis and other oral complications
The oral mucosa is vulnerable to the effects of chemotherapy and radiotherapy because of its rapid growth and cell turnover rate. Radiotherapy also interferes with the production of saliva and may increase oral complications because of a consequent reduction in the protective effect of the saliva. It is crucial to manage oral complications effectively because patients may experience considerable discomfort or develop secondary infections from the disruption of the oral mucosa. The likelihood of the development of stomatitis from a drug is dependent on the agent, the dose, and the schedule of administration. Continuous rather than intermittent administration is more likely to cause stomatitis with the antimetabolites.
Specific chemotherapy agents that may cause stomatitis include the following:
Antimetabolites: methotrexate, fluorouracil (particularly continuous infusion), capecitabine, cytarabine, irinotecan
Antitumor antibiotics: doxorubicin, idarubicin, dactinomycin, mitomycin, bleomycin
Plant alkaloids: vincristine, vinblastine, vinorelbine
Taxanes: docetaxel, paclitaxel Alkylating agents: high doses of busulfan, cyclophosphamide
Biologic agents: interleukins, lymphokine-activated killer cell therapy
Prevention and early detection. If oral complications are anticipated, it is important to implement a good oral hygiene program before the initiation of therapy. Dental consultation is recommended in specific groups of patients, including those undergoing bone marrow transplant and those with leukemia or head and neck malignancies. Maintaining good nutrition and dental hygiene is also a primary preventive measure. Normal saline is the preferred mouth rinse. Alternative rinsing agents such as sodium bicarbonate or nonalcoholic mouthwashes, if preferred by patients, may be used. Chlorhexidine and hydrogen peroxide mouth rinses should not be used. For patients receiving bolus fluorouracil, it is recommended that patients perform oral cryotherapy. This involves holding ice chips in the mouth starting 5 minutes before the bolus of fluorouracil and for 30 minutes after the administration of the drug. This intervention is effective for bolus administration only, and should not be done when oxaliplatin is also given because of the potential for increase in acute neurotoxicity. Systematic oral assessments should be integrated into the physical examination at regular intervals. Special attention should be given to the tongue, the gingiva, the buccal mucosa, the soft palate, and the lips. It is also important to assess the patient for soreness, functional ability to swallow, and any effects on eating.
Management of oral complications. Although the primary goal is prevention, once oral complications develop, the focus of care should shift to the continuation of good oral hygiene and treatment of symptoms. Agents used for oral care are categorized according to function: cleansing agents, lubricating agents, analgesic agents, and preventive agents. Table 27.7 lists several commonly used agents. Commercial mouthwashes and lemon glycerin swabs are not recommended for use because of their irritating and drying effects. If painful ulcerations do develop, topical relief may be best obtained by using single agent topical analgesics such as UlcerEase (Med-Derm Pharmaceuticals, Johnson City, TN) or lidocaine. Compounded analgesic mouth rinses such as magic mouthwash consisting of various components such as lidocaine, diphenhydramine, antacids, and/or sodium bicarbonate do not have established data to recommend in practice. Systemic pain control measures such as oral or parenteral narcotics should be implemented if topical analgesics are ineffective.
Xerostomia that follows radiation therapy to the mouth area may require treatment with artificial saliva. It may also be benefited by the administration of pilocarpine 5 to 10 mg PO t.i.d. before meals. Before the initiation of radiation therapy to the head and neck area, dental consultation is necessary to evaluate oral hygiene, the state of repair of the teeth, and the health of the gums. Amifostine shows promise as a protective agent for xerostomia and is used concurrently with radiation to the head and neck.
Secondary oral infections should be treated promptly and as accurately as possible. Fungal infections may be treated with nystatin suspension, clotrimazole troches, or
Table 27.7. Agents for oral care
Patients with dentures may be encouraged to remove them during the period after chemotherapy when they are at risk for infection, except at mealtime. In addition, the dentures should be cleansed before use. Although removal of the dentures may be detrimental to the patient's selfesteem, irritation of the dentures may lead to inflammation, ulceration, and secondary infection.
Chemotherapy-induced hair loss is not necessarily a serious physiologic complication, but psychologically, it can be one of the most devastating side effects. Partial or total hair loss can contribute to a perceived negative body image owing to the emphasis placed on the hair and overall appearance in society. The hair loss from chemotherapy, which often occurs 2 to 3 weeks after chemotherapy, is usually temporary. Hair growth begins in approximately 1 to 2 months after the treatment is completed, but it may be approximately 4 to 5 months before the patient will feel comfortable not wearing a wig. The new hair may have a different texture or color from its pretreatment characteristics. In addition to scalp hair loss, it is important to remind patients of the hair loss that may occur in other areas such as the eyebrows, eyelashes, axilla, pubis, and other fine hair.
Specific chemotherapy agents with a high potential of causing alopecia include doxorubicin, cyclophosphamide, ifosfamide, vincristine, and paclitaxel. Other drugs capable of causing alopecia include bleomycin, dactinomycin, daunorubicin, etoposide, vinblastine, methotrexate, and mitoxantrone. The extent of alopecia depends on the mechanism of the drug, the dose, the serum half-life, the infusion technique (bolus vs. continuous infusion), and the use of combinations of drugs.
Nursing interventions start with informing and preparing the patient for the possibility of alopecia. It is helpful to encourage purchasing wigs and other head wear before the alopecia occurs so that the hair color and style may be used in selecting a wig as well as allowing time for adjustment. It is important to encourage discussion of feelings regarding the hair loss for both men and women and to recognize their concerns and fears. The American Cancer Society's program Look Good, Feel Better is helpful in providing guidance about wigs, makeup, and skin care. Scalp hypothermia has been used in the past as an attempt to restrict the circulation to the scalp, with the goal of minimizing alopecia. Because of the concern for scalp metastases and sanctuary sites, scalp hypothermia is no longer recommended.
Among the many causes of diarrhea in patients with cancer are chemotherapy, radiotherapy, the cancer itself, medications, supplemental feeding, and anxiety. Osmotic
Chemotherapy and biologic agents may contribute to the development of diarrhea and most commonly include the antimetabolites such as fluorouracil, capecitabine, methotrexate, cytarabine, and irinotecan. In addition, agents such as dactinomycin, floxuridine, hydroxyurea, idarubicin, the nitrosoureas, and paclitaxel cause diarrhea relatively frequently. When diarrhea from fluorouracil, floxuridine, or irinotecan is present while on therapy, it is a sign of toxicity that must be monitored closely and that could escalate to severe levels at which the drug might need to be held or discontinued. With the increased use of biologic agents, diarrhea has been noted with interferon- and interleukin-2. High-dose chemotherapy regimens used in stem cell transplantation may also be associated with severe diarrhea and may be caused by acute graft-versus-host disease.
Assessment of a patient experiencing diarrhea should begin with a baseline history of usual elimination patterns, pattern of symptoms, and concurrent medications. The duration of the diarrhea and frequency of stool passage should be noted with reference to a stool diary if indicated. Physical examination may disclose abdominal tenderness, signs of dehydration, and disruption in perianal or peristomal skin integrity. Laboratory data may be obtained to assess serum chemistries, complete blood count, and stool samples for Clostridium difficile toxin and other enteropathic bacteria.
Management of treatment-related diarrhea is often symptomatic and requires little or no alteration in cancer therapy. Agents that decrease bowel motility should not be used for longer than 24 hours unless significant infections have been excluded. In the absence of obvious inflammation and infection, it is appropriate to treat most patients with nonspecific treatment for diarrhea, including opioids (loperamide, diphenoxylate, and codeine), anticholinergics (atropine, scopolamine), or both. More recently, it has been recognized that octreotide is often effective in
Table 27.8. Pharmacologic management strategies for diarrhea
In patients whose cancer has resulted in debility or immobility or in those who require narcotic analgesics, constipation can be a particular problem. Constipation may also develop in patients who have received neurotoxic chemotherapy agents including the vinca alkaloids, etoposide, and cisplatin, each of which may cause autonomic dysfunction. Decreased bowel motility due to intra-abdominal disease,
Docusate sodium 100 mg b. i.d. alone or with casanthranol (Peri-Colace), 1 capsule b.i.d.
If no bowel movement, add:
Senna at bedtime (dose varies with the preparation), or
Milk of magnesia 30 mL at bedtime
If no bowel movement with the above, the following may be added:
Bisacodyl one to three tablets or one 10-mg suppository, at bedtime, or
Lactulose one to four tablespoons daily
Other more aggressive alternatives, if there is no impaction, include the following:
Magnesium citrate 1 bottle
E. Altered nutritional status
Patients with cancer often experience progressive loss of appetite and sometimes severe malnutrition during the course of the disease and treatment. Malnutritionmay result from a side effect of the therapy or a direct effect of the cancer (e.g., gut obstruction or hepatic or brain metastases). The resulting effects of malnutrition are a poorer response to therapy, increased incidence of infections, and an overall worsening of patient well-being. Many times, one of the presenting signs that lead to the diagnosis of cancer is weight loss; therefore, the patient is most likely experiencing some alteration already in nutritional status. Malnutrition is reported to occur in 50% to 80% of patients with advanced disease. Nutritional management of the patient with cancer involves early intervention using a supportive health care team.
Effects of chemotherapy and radiation therapy on nutrition. Chemotherapy has a major effect on nutritional status because of the direct insult on the gastrointestinal tract. Among the gastrointestinal effects are anorexia, nausea, vomiting, taste alterations, stomatitis, esophagitis, colitis, constipation, and diarrhea. Not only are the effects physiologic in nature, but also the added psychologic impact of the disease and therapy can result in anxiety and depression, which can contribute to the lack of interest in food.
Nutritional assessment. Early in the patient's treatment, a thorough nutritional assessment should be completed by the health care team. The assessment should include diet history, nutrient intake, anthropometric measurements (height, weight, and skin-fold thickness and midarm circumference, if possible), laboratory tests for
Nutritional intervention. Nutritional intervention should be considered during the initial and ongoing assessments. Situations that warrant nutritional intervention include involuntary weight loss (more than 10% within the last 6 months, especially when combined with weakness and fatigue), history of recent physiologic stress, serum albumin below 3.2 g/dL, or severe immunocompromise. Nurses, dietitians, and even family members can identify problems and may be the first to act to promote weight gain. Various approaches that help increase weight are changes in diet; symptomatic treatment of nausea and vomiting, stomatitis, and other gastrointestinal effects of chemotherapy, and supplemental nutrition.
Nutritional supplements. Several nutritional supplements are commercially available for oral use. One benefit of nutritional supplements is that they are a concentrated form of nutrition for protein and calories. Some of the disadvantages are the unappealing taste and the high cost to the consumer. Some patients and their families are able to develop some creative highprotein and high-calorie supplements using household items with some suggestions from the health care team.
Tube feedings. Enteral nutrition through a nasogastric or gastrostomy tube may be an alternative if oral intake is not possible. Enteral feedings are the recommended route if the gastrointestinal tract is functional. Advantages of enteral feeding include lower cost and fewer complications than with parenteral feedings and maintenance of normal gastrointestinal function. Some care and maintenance are involved with feeding tubes, and patients and their families need to be given information regarding available options for feeding.
Total parenteral nutrition (TPN). Parenteral nutrition should be considered in patients who do not have a functioning gastrointestinal tract or in those for whom supplemental nutrition is anticipated for a short period of time. Patients who receive TPN usually require the insertion of a central venous catheter, which may result in other iatrogenic complications such as pneumothorax, vein thrombosis, and catheter-related infections. In many situations, TPN used in the patient with cancer increases morbidity, especially from infection, without improving survival. Thus, TPN has considerable economic, ethical, and medical consequences that must be evaluated in conjunction with the patient's overall prognosis.
Pharmacologic interventions. A recent area of interest is pharmacologic appetite stimulation. One of the agents currently used is megestrol acetate oral suspension
The incidence of neurotoxicity associated with chemotherapy is increasing, potentially because of the greater use of high-dose chemotherapy and newer drugs causing neurotoxicity used in combination. In many cases, early detection and treatment of neurotoxicity (i.e., reduction of drug dose or discontinuation) allow for the reversal of symptoms. The neurotoxic symptoms may manifest as altered level of consciousness or coma, cerebellar dysfunction, ototoxicity, or peripheral neuropathy, which may be temporary but can cause significant changes in functional ability that persist as a long-term effect. It is also important to assess renal function because poor renal function may reduce clearance of the chemotherapy agent, leading to increased neurotoxicity.
Chemotherapy and biologic agents with known potential for neurotoxicity include high-dose cytarabine, high-dose methotrexate, vincristine, vinblastine, vinorelbine, ifosfamide, cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, procarbazine, bortezomib, thalidomide, interleukin 2, and the interferons.
Prevention and early detection of neurotoxicity is key to prevention of permanent neurologic damage. Assessment of symptoms of neurotoxicity should be documented on a routine basis. In certain treatment regimens, altering the drug sequence can markedly decrease the symptoms.
Management of peripheral neurotoxicity is being studied, with the goal of slowing, halting, and reversing the neuropathy. One agent that has shown some activity with mixed results is the cytoprotectant amifostine. Pyroxidine or vitamin B6 may also be used, 100 mg b.i.d., in an attempt to minimize peripheral neuropathy. Glutamine has been shown to reduce peripheral neuropathy associated with paclitaxel. If pain becomes a major concern, anticonvulsants (gabapentin or carbamazepine) or tricyclic antidepressants (amitriptyline) may also be used. The drug pregabalin (Lyrica), similar to gabapentin, has shown promise in postherpetic neuralgia and in diabetic neuropathy, and has increasing attention in chemotherapy-induced neuropathy. Dosages of 75 mg b.i.d. have been effective, with improvements observed within 1 week of starting pregabalin. Whether there is any advantage over gabapentin is not clear. Topical analgesics and opioids may also be effective. Conventional nondrug interventions with some report of effectiveness include exercise, physical therapy, massage, and transcutaneuous electric nerve stimulation (TENS).
G. Palmar plantar erythrodysesthesia or hand foot syndrome
Palmar plantar erythrodysesthesia (PPE) is not a new side effect due to cancer chemotherapy. It has been seen with continuous-infusion fluorouracil in the past but has captured attention recently because of a high incidence with some newer chemotherapeutic drugs such as capecitabine and liposomal doxorubicin. PPE is a toxic drug reaction that begins
Prevention or minimization of PPE has been observed through regional cooling during the infusion of pegylated liposomal doxorubicin by having patients keep ice packs around the wrists and ankles, and consume iced liquids. These interventions were continued for 24 hours after completion of the chemotherapy. In this study, regional cooling decreased the frequency and severity of PPE in 94% of the patients in the intervention group. Although this is a single study, the minimal cost, relatively simple procedure, and well-tolerated intervention may be helpful.
Chemotherapeutic agents with a known potential for the development for PPE include fluorouracil (primarily with continuous infusions), capecitabine, doxorubicin, and liposome-encapsulated doxorubicin.
Clinical findings of PPE include tingling, numbness, pain, dryness, erythema, swelling, rash, blister formation, and pruritus of the hands and feet. Clinical knowledge of the potential for PPE and early assessment is imperative for adjustments of dose or withholding of therapy. Table 27.9 shows a staging scale that can be utilized to evaluate functional and clinical criteria for dose modification.
Management of PPE and symptomatic treatment result from prompt identification of symptoms. At the first sign of PPE, the drug should be stopped, or the interval between doses should be increased, or the drug dose should be reduced. If identified at grade 2 toxicity, symptoms typically improve within a few days of stopping the drug. If
Table 27.9. Hand foot syndrome (palmar plantar erythrodysesthesia) grading scale
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