HORMONE REFRACTORY PROSTATE CANCER
`
`0094-0143/99 $8.00 + .OO
`
`SUPPORTIVE CARE, PAIN
`MANAGEMENT, AND QUALITY OF
`LIFE IN ADVANCED PROSTATE
`CANCER
`
`Peg Esper, MSN, RN, CS, AOCN, and Bruce G. Redman, DO
`
`Of the 184,500 patients anticipated to be
`diagnosed with prostate cancer in 1998, ap-
`proximately 20% will have metastatic disease
`at the time of diagnosis.46, s1 Although re-
`search continues to identify new treatment
`options for this population, the fact remains
`that most patients will be affected to some
`degree by pain and other symptoms with a
`subsequent effect on the quality of life. Health
`care providers who take care of patients with
`advanced prostate cancer need to develop
`strategies in the area of pain and symptom
`management to care effectively for these pa-
`tients and improve their quality of life. Cur-
`rent concepts and reports of ongoing research
`in each of these three areas are the focus of
`this article.
`
`SUPPORTIVE CARE
`
`Supportive care for the patient with ad-
`vanced prostate cancer involves the manage-
`ment of symptoms that are experienced by
`individuals with cancer in general as well as
`those unique to the individual with advanced
`prostate cancer. The following sections dis-
`
`cuss management strategies for the following
`manifestations: fatigue, anemia, anorexia,
`lymphedema, urinary dysfunction, rectal ob-
`struction, hot flashes, spinal cord compres-
`sion, and depression.
`
`Fatigue
`
`Fatigue can be one of the most distressing
`cancer-related phenomena. Some reports have
`estimated the prevalence of fatigue to be as
`high as 99% in the cancer population.h Re-
`search in the area of cancer-related fatigue
`has shown it to be multidimensional in etiol-
`ogy. In advanced prostate cancer, fatigue has
`been attributed to several factors. Anemia is
`common in prostate cancer and is a known
`contributing cause for fatigue.sn Other poten-
`tial sources for fatigue include those induced
`by chemotherapy or radiotherapy. Greenberg
`
`and ~ o - w o r k e r s ~ ~ reported increased fatigue
`in patients receiving local radiotherapy,
`which seemed to be associated with increased
`interleukin-1 beta levels.32 Patients with rap-
`idly progressive disease experience a cata-
`bolic state of unclear etiology. These states are
`
`From the University of Michigan Comprehensive Cancer Center, AM Arbor, Michigan
`
`UROLOGIC CLINICS OF NORTH AMERICA
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`VOLbME 26 - YUMBER 2 0 MAY 1999
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`ESPER & REDMAN
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`generally associated with the production of
`glycoproteins such as tumor necrosis factor
`alpha and can lead to a debilitating fatigue as
`well.’x The management of fatigue in individ-
`uals with cancer has been an area of greater
`focus in oncology research over the last sev-
`eral years. Although recognition of this phe-
`nomenon is undebated, the management of
`fatigue remains an elusive goal in supportive
`care. For each of the other symptoms ad-
`dressed herein, one or more therapies have
`demonstrated effectiveness in their manage-
`ment; however, fatigue has no prescribed al-
`gorithm for management. Each situation must
`be reviewed and evaluated for contributing
`factors. If anemia is present, attempts can be
`made to correct it. Fatigue associated with the
`side effects of analgesics or antiemetics can
`be addressed by changes in medication. Im-
`proving hydration can be of benefit in fatigue
`associated with the byproducts of catabolic
`wasting. Most frequently, the etiology of an
`individual’s fatigue is multidimensional in
`nature, and several approaches, both pharma-
`ceutical and nonpharmaceutical, may be nec-
`essary to provide effective support for what
`is a challenging problem.
`
`Anemia
`
`The anemia of advanced prostate cancer
`has been discussed in regards to its associa-
`tion with fatigue. Anemia also contributes to
`complaints of weakness, shortness of breath,
`hypersensitivity to cold, and tachycardia. The
`presence of prostate cancer cells in the bone
`marrow replaces the normal marrow respon-
`sible for red blood cell production. Anemia in
`prostate cancer has also been tied to complete
`androgen blockade. Strum and co-workers66
`found that of 133 evaluable patients undergo-
`ing complete androgen blockade, 13% experi-
`enced a decline in hemoglobin of 25% or
`greater. The usual normochromic normocytic
`anemia reversed after discontinuation of com-
`plete androgen blockade. A similar study by
`Asbell and co-workers4 found that combined
`androgen blockade led to anemia in 75% of
`patients treated for 2 months in comparison
`with less than 5% of patients treated with
`goserelin acetate alone.
`
`For patients with hormone-refractory dis-
`ease, maintaining a luteinizing hormone-
`releasing hormone agonist without a periph-
`eral androgen blocker may be beneficial in
`limiting anemia owing to complete androgen
`blockade. For patients in whom anemia is
`more directly related to marrow depression,
`failure, or both, supportive treatment may be
`necessary. Blood transfusions can help im-
`prove the quality of life for individuals in
`whom anemia causes physiologic symptoms.
`Most institutions have a standard related to
`the minimal hemoglobin/hematocrit level
`that must be met to prescribe blood transfu-
`sions. The general principle followed at the
`authors’ center is to base the decision to trans-
`fuse more on patient symptomatology than
`on laboratory values alone. Individuals with
`a very gradual decline in hemoglobin levels
`may be able to compensate physiologically
`and will not note significant benefit from
`blood transfusions, whereas patients with the
`same hemoglobin levels who have experi-
`enced a more rapid decline from baseline may
`be very symptomatic and experience less-
`ening of symptoms following transfusion.
`The use of erythropoietin in this setting is
`becoming increasingly popular. Strum and
`co-workersh6 found that subcutaneous admin-
`istration of recombinant human erythropoie-
`tin was effective in correcting anemia and its
`associated symptoms. Similar results regard-
`ing the use of erythropoietin in the anemia of
`prostate cancer are reported by Beshara and
`co-workers.5, 6 h For patients with advanced
`prostate cancer, the cost-benefit ratio of this
`therapy should be taken into consideration
`prior to the initiation of treatment.
`
`Anorexia
`
`Anorexia was one of the ten most fre-
`quently described symptoms in patients with
`advanced cancer in a study conducted by
`Donnelly and Walsh.2’ It was also found to
`be associated with reduced survival. The
`pathophysiology of anorexia is thought to be
`related to tumor-induced metabolic effects,
`such as increased plasma-free tryptophan and
`plasma ammonia, as well as various immune
`responses.”, No significant benefit has been
`
`

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`CARE, PAIN MANAGEMENT, AND QUALITY OF LIFE IN ADVANCED PROSTATE CANCER
`
`377
`
`reported with the use of aggressive parenteral
`nutrition to increase survival or provide im-
`provement in symptoms for these patients";
`however, several pharmaceutical agents have
`been shown to help increase caloric intake
`and weight gain. Megestrol acetate (standard
`dose of 800 mg/20 mL per day) has been
`found to be an effective agent in the manage-
`ment of cancer-related anorexia in several
`studies.', -I7, ;'I Other agents such as dronabinol
`and corticosteroids have demonstrated posi-
`tive effects in appetite stimulation and weight
`gain. The doses required for a sustained bene-
`fit, however, can result in unwanted side ef-
`fects, such as mood alteration, dizziness, and
`fluid retenti~n.~',"'' Other agents such as pen-
`toxifylline, hydrazine sulfate, and cyprohep-
`tadine, initially thought to be effective agents
`in this setting, have failed to produce desired
`31, 45, '*
`results in clinical
`
`Lymphedema
`
`The lymphedema associated with prostate
`cancer is generally referred to as a secondary
`type. It is an accumulation of lymph fluid in
`the interstitial spaces that is generally caused
`by obstruction of the lymphatic system as a
`result of malignancy or scar tissue (such as
`that sometimes seen with radiotherapy).
`In mild forms, simple directions to keep
`the limb elevated above the heart, avoid con-
`strictive stockings, and monitor for signs of
`infection may be adequate. As lymphedema
`becomes more severe, measures such as cus-
`tom-fitted, graded pressure garments or se-
`quential pneumatic compression pumps may
`be warranted. Most pharmaceutical attempts
`at control (with the exception of antibiotic
`treatment in patients with cellulitis) offer little
`or no benefit and may have undesired side ef-
`fects.'
`Patients with advanced prostate cancer and
`lower-extremity edema may also experience
`protein deficiency secondary to anorexia and
`cachexia syndromes. In this setting, fluids
`may pass into interstitial tissue as a result of
`their higher colloidal osmotic pressure. Pa-
`tients should be encouraged to maintain diets
`high in protein to help maintain adequate
`levels of serum albumin. The potential for
`
`deep vein thrombosis should be included in
`the differential diagnosis, especially in indi-
`viduals exhibiting unilateral edema.
`
`Urinary Symptoms
`
`Urinary sequelae in advanced prostate can-
`cer can include incontinence, hematuria, and
`obstruction. The incidence of ureteric obstruc-
`tion ranges from 2% to 51Yi7' This event can
`occur secondary to tumor invasion of the tri-
`gone region or by compression as a result of
`local adenopathy. Resultant deleterious ef-
`fects on kidney function can occur, and an
`evaluation of renal function should be carried
`out on a regular basis to help prevent irre-
`versible complications.
`The onset of acute urinary retention may
`be drug-related, tumor-related, or indirectly
`caused by tumor compression on the spinal
`cord. Steps should be taken to isolate the
`cause of acute retention problems prior to the
`initiation of treatment.
`Multiple methods have been studied to ad-
`dress the problem of ureteral obstruction
`within the growing field of endourology.
`Chefchaouni and co-workers'3 have described
`a procedure whereby endoscopic ureteroneo-
`cystostomy is performed to obtain a patent
`ureteral orifice. In 76% of the 31 operations
`performed, continuity was restored.I3 Lopez-
`Martinez and colleagues5" described the use
`of metallic stents to bypass malignant ureteral
`obstruction in a cohort of eight patients, with
`the average duration of stent patency lasting
`19 months.
`The use of dexamethasone to relieve ure-
`teric obstruction in acute renal failure has
`been shown to eliminate the immediate need
`for urinary diversion in patients with bilateral
`
`ureteric obstr~ction.~~ Percutaneous nephros-
`tomy should still be considered in these indi-
`viduals as a reasonable alternative in the pres-
`ence of obstruction.
`Hematuria typically is the result of internal
`growth of the prostate into the urethral me-
`atus or of metastatic deposits within the wall
`of the bladder. Hematuria can be an ex-
`tremely frightening event for patients and
`caregivers. The presence of a small amount of
`blood in the urine can make it appear as
`
`

`
`378
`
`ESPER & REDMAN
`
`though the patient is actively hemorrhaging.
`Attempts to manage hematuria include three-
`way Foley catheter irrigation with the instal-
`lation of agents such as alum, silver nitrate,
`and ethamsylate.22 Cystoscopy may be bene-
`ficial to visualize and treat the source of
`bleeding. Clot formation as a result of hema-
`turia can lead to urinary retention, and con-
`tinuous irrigation may become necessary.
`Urinary incontinence can be a residual ef-
`fect of prior surgery or radiotherapy or may
`be a new manifestation of advanced disease.
`Inability to control urine flow can be very
`distressing for patients and can interfere with
`their participation in family and social activi-
`ties. The degree of incontinence should be
`assessed; in situations in which incontinence
`is in excess of either the patient's or caregiv-
`er's standards, alternatives should be consid-
`ered.
`Transurethral resection of the prostate
`(TURP) can sometimes be of assistance when
`urinary incontinence is the result of incom-
`plete bladder emptying secondary to an en-
`larged prostate; however, TURP can carry a
`risk of incontinence as well. Urinary diver-
`sions in advanced disease are generally not
`believed to be appropriate secondary to the
`decreased time of patient survival at this
`stage. In some instances, the simple measure
`of applying a Texas condom catheter to a leg
`bag can be used to help patients continue
`participation in activities they would other-
`wise avoid.
`In all cases of altered urinary elimination,
`efforts should be made to determine the
`cause. It is critical that the potential for spinal
`cord compression be assessed and given im-
`mediate attention if warranted.
`
`untreated, complete obstruction of the rectum
`is possible. A planned colostomy is a much
`better alternative than a delay that results in
`an emergency procedure to treat a complete
`obstruction. Chen and colleagues" have pro-
`posed transanal endoscopic resections of the
`prostate as a simple surgical palliation that
`can prevent the need for a colostomy. Periodic
`digital rectal examinations continue to be a
`required component of follow-up examina-
`tions even in patients with advanced prostate
`cancer to assist in early detection of im-
`pending obstruction. Patients who have never
`received prostatic irradiation may be candi-
`dates for palliative radiotherapy in this set-
`ting. In patients who present with urinary
`obstruction symptoms secondary to prostate
`enlargement at the same time as rectal ob-
`struction, TURP should be performed with
`caution to prevent urethroperineal or urethro-
`rectal fistulas.72
`
`Hot Flashes
`
`Hot flashes are one of the undesired out-
`comes of surgical or pharmacologic androgen
`blockade. These can be severe enough to af-
`fect a patient's quality of life significantly.
`This vasomotor syndrome can be treated with
`progestational agents, which have the effect
`of releasing opioid peptides at the hypothala-
`mic level, leading to a decrease in cate-
`cholamine levels. Some of the agents used
`successfully in this setting include medroxy-
`progesterone acetate, cyproterone acetate, and
`megestrol acetate.", 61 In a recent report, hot
`flashes were relieved with the serotonin-spe-
`cific reuptake inhibitor sertraline.M
`
`Rectal Obstruction
`
`Spinal Cord Compression
`
`Rectal obstruction may be the first clinical
`symptom of disease in as many as 50% of
`patients with advanced prostate cancer.72 In-
`dividuals may present with severe obstruc-
`tive symptoms, such as pain, tenesmus, and
`rectal hemorrhage, or may be almost totally
`asymptomatic. Many patients will have al-
`ready failed hormonal therapy, and addi-
`tional treatment will need to be considered. If
`
`In approximately 7% of patients diagnosed
`with prostate cancer, a spinal cord compres-
`sion will develop.ss Spinal cord compression
`is considered an oncologic emergency and
`should be treated immediately. The hallmark
`symptom of spinal cord compression is back
`pain. This may be found as an isolated symp-
`tom or may be seen in conjunction with par-
`esthesias, bowel or bladder dysfunction, or
`
`

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`CARE, PAN MANAGEMENT, AND QUALITY OF LIFE IN ADVANCED PROSTATE CANCER
`
`379
`
`weakness in an extremity. Any suspicion of
`potential spinal cord compression should be
`investigated by performing MR imaging of
`the area in question.
`Once the diagnosis of compression is con-
`firmed, steroid therapy should be initiated.
`Individuals who have not had prior hormonal
`blockade should begin androgen-deprivation
`therapy. The option of surgery versus radio-
`therapy is largely dependent on tumor loca-
`tion, size, and the patient’s general health
`status. Functional prognosis has been found
`to be correlated with the patient’s ability to
`ambulate pretreatment.h2 Early return of mo-
`tor function has been shown to be a predictor
`of long-term functional improvement.3h
`
`able or is unfamiliar with the management of
`patients with these symptoms. Referral for
`psychiatric consultation should also be made
`for patients who appear acutely suicidal or if
`initiated treatment measures provide no ben-
`efit following 2 to 4 weeks of treatment.2”
`A variety of agents exist for the treatment
`of cancer-related depression. Their selection
`is greatly dependent on the type of symptoms
`experienced by the patient and the health
`status of the individual. One must consider
`the agent’s onset of effect, potential side ef-
`fects, and the specific symptoms being tar-
`geted.40 Table 1 lists some of the common
`antidepressant agents along with advantages
`and disadvantages of their use.
`
`Depression
`
`PAIN MANAGEMENT
`
`Although not all individuals with ad-
`vanced cancer experience depression, an esti-
`mated 15% to 25% of patients sustain a clini-
`cal depression that would benefit from some
`form of t~eatment.~’.
`63 Symptoms of depres-
`sion beyond the normal adjustment to illness
`can include feelings of hopelessness, suicidal
`ideations, loss of pleasure in activities, and
`inappropriate guilt. Symptoms, unless jeop-
`ardizing patient safety, should be of at least 2
`weeks’ duration, and direct connection with
`the illness or side effects of treatment should
`be ruled out prior to considering treatment.
`The patient experiencing depression may
`need to be referred for psychiatric counseling
`if the primary care physician is not comfort-
`
`Approximately 75% of patients with any
`advanced cancer will experience pain.42
`Twenty-five percent of all patients with can-
`cer die without adequate pain relief.73 Al-
`though not all patients with advanced pros-
`tate cancer will experience pain, because
`prostate cancer has a propensity for metasta-
`sis to bone, many patients unfortunately ex-
`perience varying degrees of discomfort, with
`pain management being a significant problem
`of care.2
`Pain syndromes are classified as somatic,
`visceral, or neuropathic. In the bony metasta-
`sis of prostate cancer, patients experience a
`somatic type of pain that is characterized as
`dull, gnawing, or sharp. An inflammatory
`
`Table 1. COMMONLY USED ANTIDEPRESSANTS
`
`Classification
`
`Advantages
`
`Disadvantages
`
`Tricyclic antidepressants
`(amitriptyline, imipramine,
`nortriptyline, doxepin)
`
`Second generation (bupropion,
`trazodone)
`
`Sleep and appetite may improve
`immediately
`
`Fewer anticholinergic effects
`
`Selective serotonin reuptake
`inhibitors (SSRls) (fluoxetine,
`sertraline, piroxetine)
`Psychostimulants
`(dextroamphetamine,
`methylphenidate)
`
`Fewer anticholinergic and
`cardiac effects
`Safer in regard to overdose
`Can promote sense of well-
`being, increase appetite, and
`decrease fatigue
`
`Sedating, all can cause cardiac
`arrhythmias, anticholinergic
`Require several weeks for
`maximum effect
`Very sedating, higher doses of
`bupropion associated with
`increased risk of seizures
`Insomnia, nausea, and diarrhea
`(especially with sertraline)
`
`Starting
`Dosage
`25 mg daily
`
`50-75 mg
`daily
`
`20-50 mg
`daily
`
`Nightmares, insomnia, and
`psychosis are possible side
`effects
`
`2.5 mg twice
`. daily
`
`

`
`380
`
`EWER & REDMAN
`
`process is usually the underlying cause of this
`type of pain.” The physiology of the pain can
`be explained in several ways. Tumor growth
`within the bone can result in increased pres-
`sure in the marrow space, activating pain re-
`ceptors by stress on the periosteum.2‘ Pain is
`also attributed to the release of growth factors
`and the synthesis of prostaglandins, particu-
`larly, prostaglandin E2 and cytokines from in-
`creased tumor growth.5‘, 57 Pain may be a di-
`rect result of pathologic fractures associated
`with bone metastasis.
`Visceral pain may be felt by patients with
`advanced prostate cancer who have meta-
`static disease outside the bone (i.e., retroperi-
`toneal lymph node or liver metastases). This
`type of pain generally results in vague pres-
`sure sensations or deferred pain. Diaphrag-
`matic pressure from an enlarged liver may
`result in pain experienced in the right shoul-
`der.
`Many patients with advanced prostate can-
`cer experience neuropathic pain, which is
`probably one of the most difficult and under-
`treated of the pain syndromes. This type of
`pain can be caused by tumor growth ex-
`tending into nerve roots or compression of
`nerves, resulting in abnormal signaling of
`nerve impulses.’’
`
`Baseline Evaluation
`
`Critical to satisfactory management of pain
`is an adequate assessment of the individual’s
`level of pain. Essential questions include the
`locations of pain, the intensity, the duration,
`associated or precipitating factors, and the
`quality of pain. A multitude of instruments
`currently exist to measure pain in patients
`with tumors. In the absence of a given instru-
`ment, a comprehensive assessment includes
`the following questions:
`Where are you having pain?
`How long have you had this pain?
`Can you describe the pain (quality, that
`is, dull, burning)?
`Does this pain wake you at night?
`What are you currently taking for the
`pain? How often have you taken this
`medication in the last 24 hours?
`
`Is there anything else you do that helps
`decrease the pain?
`On a scale of 0 to 10 with ”0” being no
`pain and ”10” being the worst pain you
`can imagine, what has been your average
`pain level over the last 24 hours?
`It is also helpful to ask patients what types of
`pain medicines they have taken in the past
`and how beneficial they have been.
`A variety of pharmacologic and nonphar-
`macologic approaches can be taken to provide
`patients with effective pain management.
`More often than not, a combination of strate-
`gies will provide the best pain control.
`A well-accepted guideline in pain manage-
`ment is that suggested by the World Health
`Organization, which has established an ”anal-
`gesic ladder.” Pain management begins with
`a nonopioid with or without an adjuvant at
`step one, followed by an opioid for mild-
`to-moderate pain plus a nonopioid with or
`without an adjuvant at step two, and, finally,
`at the third or top step, an opioid with or
`without a nonopioid with or without an adju-
`vant for moderate-to-severe pain.74
`
`Nonsteroidal Anti-Inflammatory
`Drugs
`
`Because a large percentage of the pain asso-
`ciated with bone metastasis in prostate cancer
`is the result of inflammation within the peri-
`osteum of the bone, use of a nonsteroidal
`anti-inflammatory drug (NSAID) is an excel-
`lent starting point. NSAIDs work by affecting
`signal transduction proteins in inflammatory
`cells. They act to inhibit cyclo-oxygenase and,
`as a result, block biosynthesis of prostaglan-
`d i n ~ . ~ ?
`The duration of effect, cost of drug, suit-
`ability for long-term use, and associated side
`effects can all be issues to consider in NSAID
`selection. Table 2 provides a summary of
`some of the more commonly prescribed
`NSAIDs.
`In considering duration of effect, patient
`compliance should be evaluated. Patients
`who have a tendency to forget to take medica-
`tion may do better with a longer-acting
`NSAID such as nabumetone or naproxen
`
`

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`CARE, PAIN MANAGEMENT, AND QUALITY OF LIFE IN ADVANCED PROSTATE CANCER
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`381
`
`Table 2. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
`
`Generic Name
`
`Trade Name
`
`Dosing
`
`Choline magnesium
`trisalicylate
`Ibuprofen
`
`Trilisate
`
`Motrin, Advil, others
`
`Kctolorac trometharnine Toradol
`Ketoprofen
`Orudis
`Naproxen
`Naprosyn
`
`Nahumctonc
`
`Relafen
`
`1000-1500 mg, twice
`daily
`400-800 mg q 4 4 hours
`
`10 mg 96 hours
`50 mg q6 hours
`250-500 mg, twice
`daily
`1000 rng daily to twice
`daily
`
`Wholesale
`Cost Per
`Month74
`
`$60
`
`$35
`
`$1 50
`$190
`$65
`
`$65
`
`Comments
`
`Has some platelet-
`sparing effect
`Thrombocytopenia with
`long-term use
`NOT for long-term use
`-
`-
`
`-
`
`rather than one that requires every 4- to 6-
`hour dosing. Although some of the newer
`NSAIDs may seem to have a better side effect
`profile and increased efficacy, the ability of
`the patient to incur the cost of the medication
`must also be taken into account. Newer
`agents tend to be more expensive and, for
`patients without prescription coverage, may
`be cost prohibitive.
`Many patients may take a NSAID for a
`long duration. Even when additional analge-
`sic support is required, it is often beneficial
`to continue use of the NSAID to augment
`narcotic analgesics by maintaining the anti-
`inflammatory effect that those agents lack.
`For this reason, agents with a tendency to
`cause more severe long-term side effects, such
`as gastrointestinal irritation, may need to be
`avoided. Other side effects associated with
`NSAIDs include thrombocytopenia, de-
`creased renal perfusion, anxiety, confusion,
`and fluid retention.
`Although NSAIDs are often an adequate
`starting point in pain management, their con-
`tinued effectiveness as a single agent must be
`monitored. Recommendations from the
`Agency for Health Care Policy and Research
`call for the addition of an opioid to the
`NSAID when pain persists or increases. Un-
`less contraindicated, the NSAID should be
`continued as an adjuvant medication.42
`
`Opioid Analgesics
`
`Opioid analgesics should be included in
`the pain management armamentarium when
`
`nonopioid alternatives are no longer effective.
`Opioids work by binding to opiate receptors
`in the peripheral and central nervous system.
`Once the addition of an opioid analgesic is
`necessary, a short-acting agent is generally
`initiated first. In selecting a short-acting opi-
`oid, the same factors discussed in the section
`on NSAIDs can be applied. A wide variety of
`agents are available with their own unique
`side effect profiles. A “trial and error” ap-
`proach may be required to determine the best
`tolerated and most effective agent.
`Patients should be encouraged to keep
`track of the frequency with which they take
`pain medication. It is also helpful to have
`patients rate how their pain is affected by the
`analgesic being taken. For instance, following
`the administration of a short-acting opioid, a
`patient may note that the pain level decreases
`from 8 to 3 on a scale of 0 to 10.
`Once patients require multiple doses of a
`short-acting analgesic on a regular basis, the
`move to a longer-acting opioid may be war-
`ranted. In general, patients who continue to
`experience inadequate pain management or
`who require more than four to five doses of
`a short-acting opioid per 24 hours are appro-
`priate candidates for the addition of a longer-
`acting opioid.
`The most commonly used long-acting opi-
`oids in the authors’ practice are sustained
`release oral morphine and transdermal fen-
`tanyl. Both of these agents can become finan-
`cially burdensome for patients. Patients who
`anticipate difficulty in affording long-term
`use should be directed to the pharmaceutical
`companies manufacturing the opioid who
`
`

`
`382
`
`ESPER & REDMAN
`
`may offer financial assistance to qualified in-
`dividuals. Several factors need to be consid-
`ered in the selection of a long-term opioid.
`An oral agent requires every 12-hour dosing,
`whereas a transdermal patch is changed ev-
`ery 48 to 72 hours. The ability to obtain relief
`without the need to take oral agents may be
`a significant benefit for some patients. The
`authors’ anecdotal experience has been that
`the transdermal system provides more opti-
`mal pain relief at lower doses of narcotics for
`patients with bone metastasis. The side effect
`of urinary retention sometimes seen with
`morphine use may be a reason to select a
`transdermal system in patients at risk for uri-
`nary obstructive problems; however, skin
`temperature and moisture can affect medica-
`tion absorption. Patients who sustain persis-
`tent hot flashes, tumor fevers, or night sweats
`(often seen in advanced prostate cancer) may
`experience ineffective adherence of the patch,
`resulting in drying or more rapid absorption
`and oversedation.
`Patients given long-acting opioids should
`still have access to shorter-acting opioids for
`breakthrough pain and should be maintained
`on a nonsteroidal agent whenever possible.
`The dosing of long-acting opioids should be
`titrated based on the amount of breakthrough
`medication required. Patients who continue
`to require a significant amount of break-
`through medication should have an increase
`made in the dose of their long-acting opiate.
`Because optimal blood levels may not be ob-
`tained until 12 to 48 hours following the initi-
`ation of a long-acting opioid, dose adjustment
`during this interval should be avoided or
`made with caution.I5
`It is imperative to provide consistent fol-
`low-up and evaluation of the adequacy of
`the pain management regimen. The patient’s
`level of pain may increase or decrease sig-
`nificantly depending on disease progression
`or other treatments being employed. Caregiv-
`ers involved in the ongoing management and
`titration of narcotic analgesics must be aware
`of the dose equivalents between agents. Table
`3 lists equianalgesic doses for some of the
`commonly used opioid analgesics.
`A concern of the practitioner prescribing
`treatment as well as of many patients is that
`increasing amounts of analgesic will result in
`
`Table 3. EQUIANALGESIC TABLE
`
`Aaent
`
`Dose
`
`Hydrocodone
`Hydromorphone
`
`Methadone
`
`Morphine
`
`Morphine
`(sustained release)
`Oxycodone
`Transdermal fentanyl
`
`30 mg
`7.5 mg, oral
`1.5 mg, intravenous
`20 mg, oral
`10 mg, intravenous
`30 mg, oral
`10 mg, intravenous
`9&120 mg
`
`30 mg
`50 Pg
`
`Dosing
`Schedule
`q3-4 hours
`q3-4 hours
`q3-4 hours
`q6-8 hours
`q6-8 hours
`q3-4 hours
`q3-4 hours
`q12 hours
`
`q3-4 hours
`q72 hours
`
`addiction to narcotic medications. This con-
`cern is not warranted. True addiction does
`not occur in individuals who are using medi-
`cation for actual pain relief but is a behavior
`and psychologic disorder in which drug seek-
`ing is present. Opioid treatment for cancer
`pain does not result in addiction unless a
`history of narcotic addiction is present.49
`
`Management of Side Effects Related
`to Analgesic Administration
`
`As a result of the mechanism of action by
`which narcotic analgesics reduce pain, they
`can produce a variety of side effects. Some of
`the side effects seen most frequently include
`constipation, oversedation, and nausea. Many
`additional agent-specific side effects are pos-
`sible, and the patient should be monitored for
`these changes.
`Patients who are on a schedule of narcotic
`analgesic use must be placed on a bowel regi-
`men. The type of agents used and the fre-
`quency of administration will be determined
`by the patient’s bowel elimination history. At
`a minimum, most patients require a once-
`daily to twice-daily stool softener with the
`addition of a laxative such as magnesium hy-
`droxide as needed. Untreated constipation
`will often lead to increased pain (resulting
`from increased abdominal pressure), an-
`orexia, and early satiety. Bulk laxatives can
`sometimes worsen constipation because the
`fluid required for their effectiveness is often
`in excess of that taken in by patients with
`advanced disease and therefore should be rec-
`ommended with caution.
`
`

`
`CARE, PAIN MANAGEMENT, AND QUALITY OF LIFE IN ADVANCED PROSTATE CANCER
`
`383
`
`Oversedation may occur when opioids are
`titrated rapidly or when the patient changes
`from one analgesic to another. This can be
`avoided by using equianalgesic doses when
`switching routes of administration and by
`careful selection of the agent used. If ade-
`quate analgesia is being obtained, the dose
`If
`of the opiate may be decreased by 25'/0.''
`somnolence is excessive in the presence of
`inadequate pain control, a trial of a psycho-
`stimulant such as dextroamphetamine or
`methylphenidate may be indicated. Some pa-
`tients may require the use of a different opi-
`oid.25
`Nausea in patients with advanced cancer
`can be multicausal. In many cases, it may be
`related to opiate analgesic use. Administra-
`tion of an antinausea agent on a fixed sched-
`ule for a duration of several days followed
`by a decrease to an as needed basis may
`be sufficient for control in most patients.4z If
`regular scheduling or trials of various anti-
`emetics do not provide adequate relief, the
`use of a different opioid may be necessary.
`
`Anticonvulsant and Antidepressant
`Agents
`
`As mentioned previously, neuropathic pain
`may be felt by patients with advanced pros-
`tate cancer. This pain may result from injury
`to peripheral nerves by tumor invasion. The
`resulting pain syndromes may be less respon-
`sive to conventional opio