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Dying Of Lung Cancer

Key words: chemotherapy; hospice; lung cancer; pain management; palliation; radiation therapy

   One of the worse aspects of cancer pain is that it is a constant reminder
   of the disease and of death. Many fear the pain will become unbearable
   before death, and those of us involved in support networks have seen these
   fears proven true ... My dream is for a medication that can relieve my pain
   while leaving me alert and with no side effects. (1)

   Jeanne Stover, panel member, Clinical Practice Guideline Management of
   Cancer Pain, 1991-92

**********

The Agency for Health Care Policy and Research published guidelines (1) on management of cancer pain and dedicated the document to Jeanne Stover, a member of the panel that developed the guidelines. She had breast cancer for 23 years, 9 of them with metastatic disease, and died during her tenure as a panel member. She was like many others with similar problems. Approximately 1 million Americans will be receive a diagnosis of cancer this year. Nearly 8 million Americans have cancer or a history of cancer; half of these cases were diagnosed within the past 5 years. Cancer is the cause of death in approximately 1 of 10 people worldwide and 1 of 5 Americans. Fourteen hundred patients died of cancer each day in 1994. (1)

Lung cancer is the leading cause of cancer death worldwide. An estimated 180,000 new cases of lung cancer will be diagnosed in the United States this year, and there will be 160,000 deaths as a result of lung cancer. (2) Some patients will have disease amenable to treatment with curative intent. Most will have disease too extensive to propose treatment for cure. Some will be too ill, because of comorbid illness, to undergo treatment with curative intent for their cancer. At some time, the majority of those who receive initial treatment intended for cure will have a relapse of their cancer and eventually die as a result of it.

But dealing with lung cancer is more than just living or dying. Lung cancer is often associated with uncomfortable symptoms. Central tumors are often associated with cough, hemoptysis, dyspnea, and postobstructive pneumonia, while peripheral tumors frequently have symptoms resulting from infiltration of surrounding tissues. In patients with locally advanced disease, involvement of the pleura, chest wall, vertebrae, and brachial plexus frequently cause pain. Pancoast syndrome refers to a superior sulcus tumor characterized by pain, Horner syndrome, destruction of bone, and atrophy of small muscles of the hand. (3)

The care of patients with lung cancer requires decisions about treatment of disease for curative intent as well as treating the symptoms the patient has as a result of the disease. It involves the use of a variety of therapeutic modalities with different goals. A multidisciplinary approach, with the input of specialists in radiation oncology, medical oncology, hospice nursing, pastoral care, and social services, is often necessary to provide optimal care. In this article, we will provide an overview of several therapeutic modalities used in palliative care, including radiation therapy, chemotherapy, medications, neural blocks, and bronchoscopic techniques. We will describe the hospice benefit and provide an overview of how to integrate these palliative techniques from the time of diagnosis.

DEFINITION OF PALLIATIVE CARE

Palliative care is defined by the World Health Organization as "the act of total care of patients whose disease is not responsive to curative treatment. Control of pain, of other symptoms, and of psychological, social, and spiritual problems is paramount. The goal of palliative care is achievement of the best quality of life for patients and their families." As the goal of palliation is to relieve symptoms, the therapy should not be worse than the disease. Palliative care is therapy meant to relieve symptoms; although therapy may prolong life, this is not a requirement. Therefore, the recommended treatment should be as brief and effective as possible while minimizing untoward effects.

One question that is often asked is: "When in the course of disease does palliation begin?" The prevailing model has been one in which intent to cure or life-extending treatment is administered until very late in the disease course, when either the treatment is not having the desired effect or the patient refuses further therapy. This is followed by an abrupt shift toward palliative therapy (4) (Fig 1). This "either/or" model may not utilize palliative resources such as will be described here to provide symptom control. A better model is depicted in Figure 2, where the either/or model is replaced by a "both/and" model. (5) In this model, consideration of palliative needs is made at the time of diagnosis and throughout the disease course. Decisions regarding the proportion of treatment that is life extending vs palliative are made jointly between patients and their caregivers after careful considerations of the risks and benefits of the different treatment options. Patients may still accept life-extending treatments, such as oral antibiotics for treatment of infection near the end of life, while at the same time declining hospitalization and IV antibiotics for treatment of infection. This model introduces the concept we would like to outline below, that is "aggressive palliation." This approach would provide symptom relief much earlier in the course of the disease, even while the patient is undergoing treatment with curative intent.

[FIGURES 1-2 OMITTED]

TREATMENT OF LOCAL AIRWAY SYMPTOMS

Centrally located bronchogenic cancer is frequently associated with symptoms such as cough, hemoptysis, and, if large enough, postobstructive pneumonia. Radiation therapy has been used for palliation of such symptoms since x-rays were discovered in the late 19th century. The use of radiation for these symptoms is generally effective, with reported relief of cough in 48 to 65% and resolution of hemoptysis in 72 to 95%. (6-15) Greater doses of radiation may be more effective at treating the specific problem but are also associated with complications at a higher rate and of greater severity, namely pneumonitis and esophagitis. Severe, life-threatening pneumonitis has been reported as high as 7%, and esophagitis, of varying severity, is reported to occur in 0 to 81% of patients. (9-15)

Published trials do not reveal the optimal treatment regimens that both palliate the patients' symptoms and minimize the toxicity of treatment. This is likely because there were multiple variables that may have influenced the outcome, including the extent of disease, the presence of comorbid disease, the performance status of the patient, and treatment variables such as dose, number of treatments, and portal size. Although the studies have failed to demonstrate clearly an advantage of one regimen over another, they suggest that the use of fewer fractions in larger doses may have greater toxicity.

Current treatment regimens in the United States provide 30 Gy in 10 fractions over 2 weeks as a broad palliative regimen for ambulatory patients. Canadians commonly have used an abbreviated 20 Gy in 1 week. Europeans typically follow a regimen of 17 Gy in two fractions over 2 weeks. All of these regimens are less intensive than the standard 60 Gy in 30 fractions that is used for curative intent. Treatment that aims only at defined disease limits exposure of normal tissues and organs and minimizes toxicity. The main toxicities of radiotherapy, esophagitis and radiation pneumonitis, can be rare in patients receiving palliative radiotherapy, especially if the ports are sharply defined.

MANAGEMENT OF CANCER PAIN

Pain is a significant problem for patients with advanced lung cancer. The three main causes of malignancy-related pain are skeletal metastatic disease (34%), Pancoast tumor (31%), and chest wall disease (21%). (16) Cleeland et al (17) reported that 75% of patients with advanced cancer reported pain at some point in their course of their illness and 16% percent reported pain in the week prior to their interview. The pain was severe enough to impair function in more than one third of patients.

Between 20% and 50% of patients with lung cancer develop bone metastases, with nearly 10% suffering pathologic fractures. However, patients with bone metastases often have pain even in the absence of fractures. A careful history is often sufficient to detect patients with bone involvement with lung cancer. Frequently, patients can point to the area of involvement with great accuracy, but this is not always true, especially with rib and vertebral metastases with radiculopathy. The serum alkaline phosphatase level is generally elevated. A bone scan may confirm the diagnosis. Plain radiography may reveal lytic bone lesions and is valuable at assessing the need for prophylactic orthopedic stabilization and to define the extent of radiotherapy fields. Occasionally MRI might be needed to distinguish benign bone changes (eg, osteoarthritis) from malignant changes. In cases where there is any question, a bone biopsy can be performed.

Radiation Therapy

Radiation therapy is an excellent treatment for bone pain, with 80 to 90% of patients experiencing partial relief and 50% having complete resolution of their pain. (18-20) The most common schedule for this therapy is 30 Gy administered in 10 fractions over 2 weeks, although abbreviated courses may be used.

While radiotherapy is effective in controlling pain for isolated sites of bone metastasis, treatment of widespread skeletal disease poses a challenge for effective palliation. Bisphosphonates like clodronate and palmidronate inhibit osteoclastic bone resorption and already have an established role in the treatment of hypercalcemia associated with malignancies. Studies (21-27) have also shown that the use of bisphosphonates reduces both skeletal events and pain in patients with multiple myeloma or bone metastases from breast cancer. Data for patients with lung cancer are fewer but are also suggestive of benefit in pain management for bone metastases. (21)

Radiopharmaceutical Treatment

In recent years, there has been increasing interest in the use of therapeutic radionuclides for the management of pain from bone metastases. These agents localize at metastatic sites in the skeletal system and selectively irradiate these areas. Studies assessing the use of strontium-89 in this setting show that 60 to 90% of patients with painful osteoblastic bone metastases respond with complete or partial relief of pain, for an average duration of 3 to 6 months. (28,29) Myelosuppression is the main toxicity, with 30 to 40% reduction in baseline leukocyte and thrombocyte count, occurring usually by the sixth week. (30) Samarium-153 has provided up to 70% of patients some degree of pain relief; the majority achieve benefit within the first 2 weeks after administration. (31,32)

Pharmacologic Therapy: Oral and parenteral analgesics remain the mainstay of treatment for pain in patients with advanced lung cancer. Nevertheless, the study by Cleeland et al (17) reported that 90% of patients could have had their pain controlled with simple measures, yet 42% of those said they were not administered adequate analgesia. There were several predictors of inadequate pain management, including minorities, female subjects, and the elderly. The reality is inadequate pain relief. For some patients, the physician did not attribute the reported pain to the cancer, perhaps because these patients had a good performance status. The simple message is that pain is being undertreated.

The World Health Organization has devised a simple three-step schema, serving as a widely used guideline for pain management. (4) Step 1 involves the use of nonopioid analgesics (eg, acetaminophen or nonsteroidal anti-inflammatory drugs) for mild-to-moderate pain. These drugs may be combined with adjuvant drugs for specific indications (eg, anticonvulsants, antidepressants, and neuroleptic drugs for neuropathic pain; bisphosphonates and calcitonin for bone pain; corticosteroids). For step 2, when pain persists or is not adequately treated, a moderately potent opioid (eg, codeine, hydrocodone, oxycodone, propoxyphene) is used. These opioids are typically combined with a nonopioid analgesic and may be administered concomitantly with an adjuvant drug. In step 3, patients with uncontrolled or severe pain should receive stronger opioids, like fentanyl or morphine. Nonopioid analgesics and adjuvant drugs again may be added. Treatment guided by this strategy has demonstrated effective palliation of pain in up to 88% of patients with cancer and > 75% of cancer patients who are terminally ill. (33,34)

There are many opioid analgesics with different pharmacodynamic and pharmacokinetic properties. They are classified broadly as full agonists, partial agonists, or mixed agonist-antagonists. The equi-analgesic doses of commonly used opioids are listed in Table 1. Opioids should be administered on a regular basis with the interval between doses based on duration of analgesic effect. (1,35) The addition of immediate-release analgesics is also frequently required for treatment of breakthrough pain. The efficacy of the regimen should be assessed after steady-state dosing has been reached. The dose titration, schedule, and route of administration should be tailored to the needs of the individual patient. In general, there is no analgesic ceiling for most full opioid agonists, and dosage is limited only by the development of side effects. (1,35)

Respiratory depression is a serious side effect that occasionally occurs when pain is relieved abruptly and the sedative effects of opioids are no longer opposed by the stimulatory effects of pain (36); this can be managed by careful use of naloxone. Constipation is common with the use of opioids and may worsen with time. The discomfort associated with narcotic-induced constipation can be as debilitating to the patient as the pain itself. Prophylactic use of mild laxatives should be incorporated routinely into the patient's pain regimen. Moderate-to-severe constipation may be managed by the use of senna, bisacodyl, or lactulose (Table 2). Nausea and vomiting is another common side effect that frequently improves with time. Metoclopramide, prochlorperazine, chlorpromazine, and scopolamine are often useful in the treatment of nausea and vomiting associated with use of opioids. If the problem persists, however, an alternative route of opioid administration or the use of alternative drugs may have to be considered. Other side effects include dry mouth, urinary retention, pruritus, myoclonus, altered cognitive function, euphoria, and sleep disturbance.

The oral route is the preferred mode for delivery of opioid analgesics. If patients are not able to receive medications orally, transdermal or rectal routes may be tried. Transdermal administration (eg, fentanyl patch) that contains a 72-h depot supply of medication is a useful alternative to enteral or parenteral medication. IV or subcutaneous routes may also be used in this situation and in patients with persistent nausea or vomiting. Morphine by continuous infusion has the additional advantage of providing continuous analgesia. Changing the infusion rate will also allow rapid adjustment of analgesic effect. It can be administered in the outpatient setting by the use of a portable pump. In addition to the continuous infusion, small doses can be delivered at intervals for breakthrough pain as determined by the patient (patient-controlled analgesia). Several commonly used pain regimens are shown in Table 3.

In the event that pain cannot be controlled because dose escalation of opioids is limited by systemic side effects, epidural or intrathecal opioid therapy may be considered. Expertise in administration and stringent monitoring are required for such treatment, and it is most useful for intractable pain occurring in the lower part of the body. It involves the placement of a delivery system consisting of a catheter and a port or a pump that can be internalized for prolonged use. Intraventricular opioid, however, is useful for recalcitrant pain due to head and neck tumors or tumors affecting the brachial plexus, and it requires the placement of a ventricular catheter connected to a subcutaneous reservoir that can be accessed. (1)

The use of adjuvant drugs complements opioid and nonopioid analgesics for specific types of pain. Commonly used adjuvant medications are listed in Table 4. Of particular interest is the use of corticosteroids. Dexamethasone is the frequently used form, and it has a wide range of effects that are useful in symptom management in patients with advanced lung cancer. In a study by Robertson et al, (37) 20 lung cancer patients were administered oral dexamethasone, 8 mg bid. Ninety percent of the patients required pain medications at baseline. Twenty-four hours after commencement of dexamethasone therapy, there was significant improvement in pain. Less is known about the long-term side effects of steroid therapy in this patient population; however, if the patient's disease is terminal, the risk/benefit ratio appears to be acceptable.

Neuroablative Techniques

Neural blockade, in experienced hands, can sometimes control intractable pain when all other therapies fail. Temporary block with a local anesthetic is usually applied prior to a planned neurolytic block to assess side effects as well as to predict the likely outcome. Neurolytic block using phenol or alcohol can be applied to peripheral nerves, nerve plexus, or nerve roots in the spinal canal; 50 to 80% of patients receiving such treatment may derive benefit. (1) For patients with chest wall pain due to tumor invasion from lung cancer, neurolysis of intercostal nerves, or chemical rhizotomy (by injecting small volumes of a neurolytic agent into the epidural or intrathecal space) may provide significant pain relief for a period of time. It is exceedingly rare for someone to need this type of pain management. One survey reported that only 16 of 1,205 patients required intraspinal treatment to control pain. (38)

Neurosurgical intervention is sometimes considered for patients in whom more conservative approaches have failed. In a small series of 14 patients with chest wall pain due to malignancy, Arbit et al (39) demonstrated excellent results in 64% after neurectomy at multiple levels. Anterolateral cordotomy selectively blocks pain and temperature sensation from the respective levels on the contralateral side of the body. (This can also be achieved by using radiofrequency ablation.) When there is bilateral pain, commissural myelotomy, which aims to disrupt crossing afferent fibers, may be considered. Surgical or chemical hypophysectomy is sometimes used for diffuse bone pain that is resistant to other therapies, but long-term pituitary hormone replacement is required after the procedure. (1)

Other techniques of pain management include the use of heat and cold therapy, transcutaneous electrical nerve stimulation, acupuncture, and psychological interventions (eg, hypnosis, relaxation, and distraction techniques). These all may serve to supplement and enhance the treatment methods already discussed. (40-43)

TREATMENT OF DYSPNEA

Dyspnea, or the uncomfortable sensation associated with breathing, is a frequent symptom in the lung cancer patient. A partial list of the reasons for dyspnea related to lung cancer or its treatment includes pulmonary embolism, superior vena caval syndrome, deconditioning, reactive airway disease, radiation pneumonitis, drug-induced pneumonitis, endobronchial obstruction, postobstructive pneumonia, hemoptysis, hemorrhage, and progression of disease. An aggressive search for the cause of dyspnea should be undertaken, for many can be effectively treated. A multidisciplinary approach is often required to both diagnose and treat the disorders that cause dyspnea in this patient population.

Advances have been made in the interventional treatment of endobronchial disease. (44) The use of endobronchial laser resection, photodynamic therapy, cryotherapy, and electrocautery followed by stent placement can relieve dyspnea and improve quality of life in the patient with endobronchial tumor obstruction. (45-57) Silicone stents can be placed through a rigid bronchoscope; self-expanding, covered metal stents can be placed through a flexible bronchoscope. The use of these technologies is now commonplace and is no longer limited to academic centers. In properly trained hands, electrocautery with tumor ablation followed by stent placement can be accomplished using the flexible bronchoscope under conscious sedation.

Pharmacologic therapy to reduce the sensation of breathlessness should also be considered. Opiates (in both controlled and uncontrolled studies) (58-61) have been shown to reduce dyspnea in patients with lung cancer. The side effects of the medications discussed earlier must be weighed against their benefits. Another commonly used class of drugs to relieve breathlessness is benzodiazepines. Although some authors have reported that the use of benzodiazepines reduced dyspnea in their patients, controlled trials (62-65) have not shown any benefit while demonstrating significant side effects. Thus, benzodiazepines are not recommended for relief of breathlessness in patients with terminal lung cancer. Oxygen is commonly used to treat dyspnea associated with lung cancer. Though this would seem obvious for the patient with hypoxia, there may also be relief of symptoms in patients without hypoxia, perhaps because of stimulation of nasal or facial receptors. Clinicians are familiar with the findings that patients with COPD report relief of their shortness of breath when sitting in front of a fan. (66) There is an increased cost associated with oxygen therapy in these patients; thus, it is recommended that a therapeutic trial of oxygen should be considered in terminal patients with lung cancer who do not respond to simple measures such as sitting in front of a fan.

TREATMENT OF CNS INVOLVEMENT

Brain metastases are common in patients with bronchogenic carcinoma. Ten percent of patients with lung cancer present with metastatic disease to the brain, and at some point during the course of their disease, 25 to 35% of patients will have brain metastases develop. (6) Half of these patients have multiple lesions. Patients can present with headaches, seizures, focal weakness, or difficulty with gait and balance. (67) Therefore, the care of these patients requires prompt intervention. Radiotherapy is often effective; two thirds of patients with serious neurologic dysfunction and one third of patients with moderate neurologic dysfunction will improve. (6) Overall, symptoms are improved between 70 to 90%. The most common radiotherapy technique is whole-brain radiation with 20 to 30 Gy in 5 to 10 fractions over 1 to 2 weeks.

Corticosteroids are often used to reduce cerebral and spinal cord edema in the presence of cerebral metastases and spinal cord compression, respectively. Treatment with steroids, which reduce edema, uses doses comparable to dexamethasone, 4 to 6 mg po qid.

ROLE OF ANTINEOPLASTIC TREATMENT

The role of chemotherapy in the treatment of advanced non-small cell lung cancer has expanded dramatically over the past several years. Chemotherapy should not only be considered for patients for whom there is an attempt to cure disease. There is now a place for chemotherapy as a palliative agent to improve quality of life in patients with lung cancer. In trials using cisplatin-based chemotherapy demonstrated only a modest survival benefit while the toxicity was significant. (68) Some clinicians may interpret these results such that treatment with chemotherapy reduces quality of life without prolongation of life, which has probably led many clinicians away from the use of cytotoxics for palliation of symptoms associated with advanced disease. In truth, the use of chemotherapy for progressive lung cancer may improve quality of life to a degree that more than offsets the negative impact of chemotherapy-associated toxicity. The newer cytotoxic agents (ie, vinorelbine, gemcitabine, paclitaxel, docetaxel, and irinotecan) became available in the 1990s and offer enhanced efficacy in terms of improved response rates and are significantly better tolerated.

Vinorelbine, a semisynthetic vinca alkaloid, was compared to supportive care alone in patients [greater than or equal to] 70 years old with advanced non-small cell lung cancer. (69) A quality-of-life analysis was performed, and functional scales were consistently superior for the vinorelbine-treated patients compared to the control patients. Gemcitabine, a pyrimidine antimetabolite, has been demonstrated in the treatment of advanced non-small cell lung cancer to ameliorate major disease symptomatology. (27,70) The taxane docetaxel has been extensively studied in non-small cell lung cancer. Two phase III studies have demonstrated effective palliation as documented by quality-of-life assessments. (71-73) When docetaxel was compared with best supportive care in patients who had previously received platinum-based chemotherapy, all of the quality-of-life parameters favored the docetaxel-treated patients, with statistically significant differences noted on the pain and fatigue scales. (71,73) Significantly fewer docetaxel-treated patients required tumor-related medication in general, and morphine or morphine-equivalent medication specifically. (71,73)

In summary, the use of chemotherapy for the treatment of non-small cell lung cancer has evolved considerably since the release of several active and well-tolerated cytotoxic agents. The favorable toxicity profiles associated with these new agents has allowed chemotherapy to assume a very prominent role in the palliation of patients with advanced disease.

HOSPICE BENEFIT

Hospice care has been available for > 50 years in Europe but was not introduced in the United States until the early 1970s. There are > 3,000 licensed hospice programs that serve a half of a million patients each year in the United States. Hospice provides palliative care, defined as treatment that enhances comfort and improves the quality of the patient's life. (74) It is perhaps the most underutilized benefit available to patients with terminal illness. The Hospice benefit is appealing to patients and caregivers because care can be delivered in the home rather than the hospital, thereby allowing death to take place in surroundings that are comforting to patients. The specialized training of the hospice staff may provide greater recognition and optimal treatment of pain. Patients and families are extremely satisfied with this benefit.

Medicare beneficiaries, who make up 80% of the hospice clientele, receive noncurative medical and support services that otherwise would not be covered. These include at-home nursing care, physician services, medical appliances, medications, short-term hospitalization, home health aides, homemakers, physical therapy, psychological therapy, speech therapy, and social services. To be eligible for hospice, the patient must be deemed terminally ill with an expected survival of [less than or equal to] 6 months. However, the patient is not denied the benefit if they live longer. In a study of > 6,000 patients entering hospice, of which 21% had lung cancer, the average survival is about 30 days and 14% of the lung cancer patients died within 7 days of being enrolled in hospice. (75) If the benefit is available to patients for 6 months, why are patients enrolled so close to death? This may be because patients resist being told their illness is terminal or physicians may want to preserve hope. Medicare regulations may discourage physicians from enrolling patients until they are "sure" that the patient is terminal. Physicians may want to continue life-extending treatments and palliate the patient at the same time, which is not allowed under current hospice regulations. Changes in the patterns of enrollment to hospice may improve the quality of terminal care and the use of hospice services should be encouraged.

CONCLUSION

There is extensive literature to guide the practicing clinician in caring for the dying patient with lung cancer. Using the techniques described herein can alleviate nearly all of the physical suffering associated with dying of cancer. We should approach the lung cancer patient in pain with the same vigor that our profession approaches a patient with sepsis admitted to the ICUs. Perhaps the term aggressive palliation would better describe the optimal role of the physician caring for patients with advanced lung cancer. We are reminded that, "The relief of suffering and the cure of disease must be seen as twin obligations of the medical profession that is truly dedicated to the care of the sick." (76)

Table 1--Opioid Analgesics, Equi-analgesic Doses

   Opioid Agonists       Parenteral, mg   Oral, mg

Codeine                       130            200
Hydrocodone                                   30
Oxycodone                                     30
Propoxyphene                                  50
Morphine                       10             30
Hydromorphone                   1.5            7.5
Oxymorphone                     1         10 (rectal)
Methadone                      10             20
Meperidine                     75            300
Levophanol                      2              4
Fentanyl (transdermal)

Table 2--Management of Opioid-Induced Constipation

Prevention *
  100 mg of docusate sodium plus 17.2 mg of sennosides po bid
  10 mg of bisacodyl po at bedtime as needed if no bowel
    movement in previous 24 h; repeat in the morning if still no
    bowel movement
Titration ([dagger])
  100-200 mg of docusate sodium plus 17.2-34.4 mg of
    sennosides po bid to tid
  10-15 mg of bisacodyl po bid to tid
Obstipation ([double dagger])
  30-60 mL of milk of magnesia plus 15-30 mL of mineral oil po
    qd or bid
  30-60 mL of lactulose po bid to qid
  8 oz (240 mL) of citrate of magnesia po qd
  Phospho-soda enema (Fleet; Lynchburg, VA) qd

* The therapeutic goal of one soft bowel movement every 1 to 2 days
is best achieved by regularly administering both a stool softener and
a bowel stimulant, with additional stimulants as needed. The
preventive regimen outlined is recommended for patients receiving
the equivalent of 120 mg/d of morphine po. Common doses are
50 mg of docusate sodium plus 8.6 mg of sennosides per tablet, and
5 mg of bisacodyl per tablet.

([dagger]) The preventive regimen should be titrated to meet the
therapeutic goal without causing cramps or requiring straining. The
dose of docusate and sennosides should be escalated before the
bisacodyl dose is escalated, to minimize cramping.

([double dagger]) Any patient who does not have a bowel movement in
any 3-day period should be evaluated for impaction and should be
disimpacted, if indicated, before receiving additional oral laxatives.

Table 3--Commonly Used Pain Regimens

     Drugs                   Route         Dose          Interval

Regimen A
  Morphine *              po            30 mg         bid
  Immediate-release       po            15 mg         Every 3 to 6 h
    morphine ([dagger])                                 as needed
Regimen B
  Fentanyl patch          Transdermal   25 [micro]g   q72h
    ([double dagger])
  Immediate-release       po            15 mg         Every 3 to 6 h
    morphine ([dagger])                                 as needed

* Morphine should be titrated up by 15 to 30 mg q12h when
breakthrough medication is needed more than 4 to 6 times per day.

([dagger]) Immediate-release morphine is used for breakthrough pain.
Patients should record the number of times this medication is required
so that the efficacy of the long-acting medication can be evaluated.

([double dagger]) This slow-release transdermal narcotic can be
increased by 25- to 75-[micro]g increments q72h.

Table 4--Adjuvant Analgesics for Management of Cancer Pain

     Class            Examples                Indications

Corticosteroids   Dexamethasone       Pain associated with brain
                                        metastases and spinal
                                        cord compression
                  Prednisone
Anticonvulsants   Carbamazepine       Neuropathic pain
                  Phenytoin
                  Clonazepam
                  Valproate
Antidepressants   Amitriptyline       Neuropathic pain
                  Desipramine
                  Fluoxetine
                  Paroxetine
Neuroleptics      Haloperidol         Resistant or unable to
                                        tolerate opioids
                  Methotrimeprazine   Has antiemetic and
                                        anxiolytic effects
Antihistamine     Hydroxyzine         Has antiemetic, anxiolytic,
                                        and sedative effects
Bisphosphonates   Clodronate          Pain from bone metastases
                  Pamidronate
Etidronate
Calcitonin                            Pain from bone metastases

ACKNOWLEDGMENT: The authors thank Mark Green, MD, Frank Brescia, MD, and Carolyn E. Reed for their thoughtful input, and Gayle Granger, Paula Rowell, and Marianne Grac for help in article preparation.

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* From the Divisions of Pulmonary and Critical Care Medicine (Drs. Silvestri and Flume) and Medical Oncology (Drs. Sherman and Leong), and the Department of Radiation Oncology (Drs. Williams and Turrisi), Medical University of South Carolina, Charleston, SC.

Manuscript received May 18, 2001; revision accepted November 16, 2001.

Correspondence to: Gerard A. Silvestri MD, FCCP, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC, 29425; e-mail: Silvestri@musc.edu

COPYRIGHT 2002 American College of Chest Physicians
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