Palliative Management of the Patient With Advanced Pancreatic Cancer

Introduction

In the United States, the care of cancer patients is a critical issue that impacts on both the medical community and society in general. The scope of this issue continues to expand due to a number of factors, including the aging of the US population and the increasing incidence of specific cancers.

It has been estimated that in 1996, 1,359,150 people will be diagnosed with cancer in the United States and 554,740 will die of this disease [1]. Thus, despite the continuing emergence of new cancer therapies, about half of all cancer patients will die of their disease. This suggests that many patients with advanced cancer will require treatment strategies focusing on symptom management, because curative strategies may not benefit them [2]. This approach will require a shift in the focus of cancer research to include studies of palliative treatment in addition to new curative regimens. Oncologists, who have been trained to concentrate on curing cancer, will be required to integrate palliative treatment strategies into patient management. These changes are likely to be affected by the increasing role of health economics in the treatment decision-making process [3].

Issues Associated with Palliative Therapy

Challenges for the Oncologist

Current approaches to palliative treatment for patients with advanced cancer are fraught with deficiencies [4]. Many physicians fail to appreciate the impact of symptoms on the patient's quality of life or may lack an understanding of how to treat the whole patient rather than just the tumor. These problems reflect a void in the oncology training curriculum [2,5]. For example, although pain is a dominant cancer symptom, pain control has only recently been included in the Medical Oncology Board examinations [4]. Furthermore, uniform clinical practice protocols for palliative treatment are lacking. Although some institutions have begun to develop these protocols, most cancer centers have not instituted systematic approaches to palliative patient management [2]. For a list of the most commom symptoms in advanced cancer patients, see Table 1 [6].

Due to the aging of the US population, oncologists will be increasingly faced with managing cancer patients who have a variety of other age-associated illnesses, including osteoarthritis, diabetes, and congestive heart failure. Oncologists will require training not only in the appropriate use of palliative treatment regimens but also in the treatment of patients with advanced cancer who have multiple diseases and associated symptoms. Overall, the clinical role of the oncologist must encompass preventive oncology, diagnostic evaluation, communication, antitumor therapies, symptom control, optimization of social supports, and care of the dying patient [2].

Measuring the Efficacy of Palliative Interventions

Measuring tumor response is a well-established means of determining the efficacy of cancer therapy. Unfortunately, there is no gold standard quality-of-life measurement to assess the efficacy of palliative interventions. Various tools have been developed to permit the systematic, reproducible assessment of patients' quality of life (Table 2) [7]. Although these assessment tools can provide useful information for the oncology researcher, the implementation of these tools in clinical practice has been difficult. For example, the instrument may not ask questions specific to the patient's particular cancer, or it may be too detailed for the patient [6]. Thus, at present, the practicing oncologist should rely on communication with patients to determine the efficacy of palliative treatment regimens.

Palliative Management of Advanced Pancreatic Cancer

While palliative interventions should be considered for all patients with advanced cancer, advanced pancreatic cancer provides a distinct challenge for the oncologist. The nonspecific and vague symptoms associated with pancreatic cancer contribute to a delay in diagnosis, and most patients are diagnosed at an advanced stage [8,9]. In its advanced stages, pancreatic cancer is associated with a plethora of symptoms that require treatment. In addition, a small number of patients have histories of substance abuse that must be considered, but this does not preclude adequate palliation [10,11].

Complications and Symptoms

The most common symptom associated with pancreatic cancer is pain, which occurs in approximately 80% of patients [6,12]. Other symptoms include anorexia, early satiety, xerostomia, sleep problems, weight loss, fatigue, weakness, nausea, and constipation. In addition to these symptoms, physical findings may include cachexia, a palpable abdominal mass, ascites, and jaundice. Metastasis to other major organs, such as the liver, lungs, lymph nodes, and bone, also can occur [12].

Pain Management

According to the World Health Organization, 20% to 50% of patients with cancer present with pain, approximately 33% experience pain during treatment of their disease, and 75% to 90% of patients with advanced or terminal cancer have pain [13]. The reasons for this problem include societal barriers due to the perceived potential for misuse of opioid analgesics, insufficient knowledge about pain control measures among health-care providers, governmental regulations, and health economics [4,14]. Physicians face a variety of obstacles when treating the patient with cancer pain, including complications from the side effects of other medications; metabolic abnormalities, such as liver dysfunction; and homebound patients with rapidly changing disease [15]. A critical component of pain management is communication and trust between the physician and the patient [16].

For the patient with advanced cancer, the goals of pain management should be to permit an acceptable level of functioning and to allow the patient to die as free of pain as possible [16]. Therapeutic options to treat cancer pain include behavior modification, standard drug therapy, experimental drugs or novel methods of drug administration, and selective anesthetic and neurosurgical approaches.

General Guidelines for Using Analgesics--Analgesic drugs can be divided into three categories: nonnarcotic analgesics (ie, aspirin(Drug information on aspirin), acetaminophen, nonsteroidal anti-inflammatory drugs) that act on peripheral pain mechanisms; narcotic agonist and antagonist drugs that interact with opiate receptors (morphine, hydromorphone(Drug information on hydromorphone), methadone(Drug information on methadone), levorphanol, oxymorphone, heroin, codeine, oxycodone(Drug information on oxycodone)); and adjuvant analgesic drugs that produce analgesia in certain pain states or potentiate opioid analgesics [16]. Unlike nonnarcotic analgesics, the dose-response relationship of opioid agonists is logarithmic, such that the increment in analgesia is linear until loss of consciousness [17]. Unfortunately, many physicians underuse opioids to treat cancer pain, probably because of controlled substance regulations and/or concerns about sedation, respiratory depression, tolerance, and addiction [11,18].

The optimal use of opioid analgesics requires maintaining a balance between their benefits and toxicities. Side effects may include nausea, vomiting, mental clouding, sedation, constipation, urinary retention, and pruritus. Appropriate strategies to manage these side effects should be anticipated for patients on opioids. Furthermore, since opioids produce different responses in different individuals, the analgesic regimen must be tailored to the patient's response, in terms of both the drug's analgesic efficacy and its side effects. It is important to note that it is rare for patients with cancer pain to develop psychological dependence on these drugs [16].

Guidelines for Using Opioids in Pancreatic Cancer Patients--Pain management in patients with pancreatic cancer is notoriously difficult. There is a history of alcohol(Drug information on alcohol) and/or benzodiazepine abuse in a significant number of these patients. Because of this, their tolerance to analgesic dosing is higher than in the typical cancer patient, and the prescriber must be prepared to use higher doses of analgesics than in patients with other common solid tumors.

No specific opiate appears to have superior activity in the setting of pain related to pancreatic cancer. The principles and practice of opiate use in this setting are similar to those in other situations, with one exception: There is a much higher risk of small bowel obstruction in patients with pancreatic cancer. Opiate-induced bowel obstruction is a preventable complication in this setting, but patients and their families must be warned specifically to watch for symptoms suggestive of bowel obstruction and to call the physician immediately should these be noted. Also, aggressive use of laxatives is essential to prevent this complication.

A specific technique that is invaluable in patients with pancreatic cancer is the continuous administration of subcutaneous opiate infusions by means of a patient-controlled analgesia (PCA) pump. This approach has the advantage of delivering analgesics reliably in patients who have impaired gastrointestinal function and for whom oral analgesics may not be the best choice. In addition, in patients who develop a bowel obstruction, a PCA pump can ensure optimal analgesia despite their inability to take liquids or food by mouth.