Palliative Pharmacotherapy: State-of-the-Art Management of Symptoms in Patients With Cancer.

BACKGROUND: Advanced cancer produces multiple symptoms as patients progress through their disease trajectory. Identifying, measuring, and providing therapy for uncontrolled symptoms becomes important because disease-altering therapies may be no longer possible. Symptoms other than pain that cause distress in patients with cancer include delirium, dyspnea, anorexia, nausea, and fatigue. Precise management of these symptoms can lead to the best possible quality of life and lessen distress. This article reviews current management strategies of these symptoms. METHODS: The epidemiology, mechanisms, assessment, and therapies of common symptoms in the advanced cancer population are reviewed. RESULTS: Identifiable approaches facilitate symptom management in advanced illness. CONCLUSIONS: Using a systematic approach to symptoms in advanced illness can improve the quality of life and lessen distress among patients with cancer and their families, friends, and caregivers.

Pharmacological Management of Cancer-Related Pain.

BACKGROUND: Pain occurs in 50% of patients with cancer at the time of diagnosis, and nearly 80% of patients with advanced stage cancer have moderate to severe pain. Assessment of pain requires the health care professional to measure pain intensity, delineate opioid responsiveness, and clarify the impact of pain on a patient's psychological, social, spiritual, and existential domains. To this end, the World Health Organization (WHO) has developed a 3-step pain ladder to help the health care professional effectively manage pain, classifying pain intensity according to severity and recommending analgesic agents based on their strength. METHODS: Health care professionals should follow the WHO guidelines to manage cancer-related pain in their patients. With regard to opioids, dosing, equianalgesic conversions, the management of adverse events, and the identification of new agents are discussed. Integrating adjuvant analgesics and interventional pain techniques into the management of cancer-related pain is also discussed. RESULTS: The WHO analgesic ladder is an effective tool for managing cancer-related pain. Successful pain management in patients with cancer relies upon the health care professional to pay attention to detail, especially during the introduction of new drugs and in identifying potential adverse events. Health care professionals must assess opioid responsiveness to determine whether adjuvant analgesics should also play a role in a patient's treatment plan. CONCLUSION: Adherence to the WHO pain ladder and understanding proper use of interventional pain techniques complement the pharmacological management of cancer-related pain.

Fentanyl (transmucosal).

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com).

Ketamine for pain: an update of uses in palliative care.

Ketamine is a lipophilic, general anesthetic. When given at subanesthetic doses, it also has been found to be an effective analgesic, with efficacy in cancer-associated neuropathic pain, ischemic pain, and regional pain syndromes. It can be administered orally, intravenously, subcutaneously, and topically, and interacts with several receptors important in pain management, most importantly the N-methyl-D aspartate (NMDA) receptor. Blockade of the NMDA receptor is associated with reversal of opioid tolerance. Ketamine is metabolized via cytochrome P450 3A4, although no significant interactions have been reported. Ketamine is considered one of the World Health Organization (WHO) essential drugs for the management of refractory pain.

Tapentadol: an initial analysis.

Tapentadol hydrochloride (17(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol) is a newly released analgesic that works at two levels: by acting as a p-opioid agonist and as a modulator of descending inhibitory pathways through its effects on neurotransmitters involved in these pathways. The theoretical advantage is the provision of synergistic analgesic activities, which may lessen the need for opioid escalation. The advantage is its potential as a possible new agent in neuropathic pain. Preclinical models confirm analgesic properties in acute pain and neuropathic pain models, but with less potency than morphine. Tapentadol has minimal CYP 450 interactions limiting potential for drug interactions. Human clinical trial data in nonmalignant pain suggest less potency than a step-3 opioid, and the drug remains to be tested in patients with cancer pain and neuropathic pain.

Palliative treatment of malignant ascites: profile of catumaxomab.

Malignant ascites is the abnormal accumulation of fluid in the peritoneal cavity associated with several intrapelvic and intra-abdominal malignancies. The development of ascites leads to significant symptoms and poor quality of life for the cancer patient. Available therapies for palliation include treatment of the underlying disease, but when there are no treatment options, the use of diuretics, implantation of drainage catheters, and surgical shunting techniques are considered. None of these symptom palliation options affect the course of disease. The development of trifunctional antibodies, which attach to specific overexpressed surface markers on tumor cells, and trigger an immune response leading to cytoreductive effects, represents a new approach to the management of malignant ascites. The purpose of this review is to highlight current therapies for malignant ascites and review data as to the effectiveness of a new trifunctional antibody, catumaxomab.

Using the values-based history to fine-tune advance care planning for oncology patients.

There is no standardized approach to the discussion of advanced care planning. One approach to discussing advanced care planning involves the use of a values history. The values history focuses on questions related to overall health, personal relationships, and independence, as well as symptoms. The values history facilitates communication with the patient and allows the patient to express their view. This approach to patient communication is less threatening to patients and does not force the patient into thinking that they need the right answer. Values-based directives are less intrusive on a doctor's skill in making appropriate clinical decisions. They ask questions that require no technical skill and are easily done by other members of the health-care team. Values histories are useful in a wide range of situations where the doctor needs to understand the patient as a person. Compared to traditional, medicalized advance directives, values histories are less subject to the objections of not being clearly established at the time of their writing, or applicable in the circumstances that subsequently arise as in this case. They can help to validate preferences about treatment and also indicate appropriate courses of action that were not, or could not, be covered by traditional advance directives alone. This article illustrates the use of a values-based history in a patient with advanced head and neck cancer.

Palliative oncology: thalidomide.

After decades of disuse because of its teratogenic effects, thalidomide has had a resurgence of use as a promising therapeutic agent for multiple myeloma. Its mechanism of action involves activation of the immune system, antiangiogenic effects, and inhibition of cytokines. Thalidomide does not interact with the cytochrome oxidase system. It is not significantly metabolized, but it does undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive. Despite the potential adverse effects of peripheral neuropathy, constipation, deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide is an effective first-line agent for multiple myeloma in combination with dexamethasone or melphalan and prednisone. It has also been studied in the palliative care of patients with cytokine-based syndromes such as anorexia-cachexia syndrome. This review describes its use in oncology, hematology, and palliative care.

Toxicity of bisphosphonates.

Bisphosphonates have become an important treatment for the palliation of metastatic bone disease. Their increasing use has lead to the recognition of toxicities that can lead to substantial morbidity for the patient with advanced cancer. This case presentation highlights toxicities associated with bisphosphonate use and provides some guidelines on the use of bisphosphonates and management of these toxicities.

Established and potential therapeutic applications of octreotide in palliative care.

Octreotide acetate was developed as a pharmacologically stable, long-acting analogue of the hormone somatostatin. Mimicking the actions of somatostatin, octreotide has been used for its antisecretory effects. Randomized control trials have established the efficacy of octreotide for malignant bowel obstruction and for chemotherapy-induced diarrhea. Octreotide has proven to be an effective agent for symptoms of carcinoid syndrome. Newer uses include for bone marrow transplantation, infectious diarrheal syndromes, and management of hepatic metastases. More evidence is needed for the establishment of its efficacy for hypercalcemia, pain, pleural effusions, diarrhea after celiac plexus block, and malignant ascites.