PALLIATIVE CARE
Progress in cancer treatment usually requires the discovery of new drugs which kill cancer cells more effectively. Scientists are rapidly unlocking the keys to cancer cell growth-identifying the critical differences between normal cells and malignant ones. The hope is that new therapies will specifically target these abnormal cell mechanisms and not damage the normal body tissues. Indeed, the first of these "designer" drugs, Gleevec, was recently developed and approved for use in one specific malignancy, chronic myelogenous leukemia. However, the remarkable success of the Gleevec story is slightly tainted by the fact that the drug does affect other cellular mechanisms, hence resulting in some toxicities, although much less than with conventional chemotherapy.
Patients with cancer live much longer today than they did 10 or 20 years ago...and their quality of life is far better. Part of this improvement is due to new cancer therapies, but additional benefit is derived from interventions that lessen symptoms (palliation) without specifically reducing the
cancer itself.
Palliative therapies include medications which improve the symptoms related to cancer progression. New methods of pain relief have provided significant benefit for one of the most devastating and feared consequences of cancer. Medications are now available to improve bone strength and prevent complications from metastatic involvement of bone. Drugs for weight loss, fatigue, nausea, and infections have all helped to lessen the disruptive effects of cancer.
Other new approaches are useful to treat the side effects and toxicities of cancer therapies. Despite the promise of targeted therapies which will be highly specific with minimal toxicity, the overwhelming likelihood is that these new drugs will be used together with standard chemotherapy and radiation. Therefore, unfortunately, the "toxic" drugs in use today will not be discarded in the near future. New growth factors have helped to ameliorate the bone marrow toxicity common to many chemotherapy agents. Drugs such as amifostine appear to protect normal tissues from radiation-damage without decreasing the ability of radiation to kill malignant cells. Numerous drugs now in clinical trials, may actually increase the ability of radiation to kill cancerous tumors ("radiation sensitizers") without adversely affecting normal cells. Below is a brief description of some palliative therapies for cancer.
Gastrointestinal toxicity can significantly affect the quality of life for cancer patients receiving chemotherapy. Serotonin antagonists (ondansetron, granisetron, dolasetron) have provided significant benefit in the immediate post-treatment interval. However, "delayed emesis" occurring 3-5 days later, has remained a troublesome toxicity with some chemotherapy drugs. A new class of drugs, substance "P" inhibitors, holds promise for treatment of delayed emesis. Several of these drugs are in late stages of development but none have been approved yet.
At this time, the best approach for treating chemo-related nausea is prevention, using a cocktail of anti-emetic agents individualized for each patient. Possible interventions include steroids (dexamethasone), sedatives (lorazepam), antihistamines, dronabinol (the active ingredient of marijuana), in addition to the traditional anti-emetics such as prochlorpromazine, tigan, etc.
Non-pharmacologic methods (acupuncture, music therapy, etc) are also useful in some patients.
New developments in chemotherapy pharmacology have also been helpful to reduce the amount of nausea and vomiting associated with currently available chemotherapy agents. Low
dose weekly schedules are now commonly used with many drug regimens yielding equal or better effectiveness against malignancy but with less gastrointestinal toxicity.
Pain is the most devastating symptom associated with cancer. Treatment of pain begins with an accurate assessment of the site of pain, intensity, and the specific etiology, whether visceral or neuropathic. Radiation is most helpful for pain that is limited to one area. Other local modalities, such as injection of anesthetics, steroids, etc often help alleviate pain for brief periods. However, effective treatment of pain in cancer patients usually also requires systemic analgesic medications.
Narcotic analgesics are the mainstay of pain control. The "gold standard" for use of narcotics is PCA (Patient Controlled Analgesia) which delivers a continuous amount of narcotic directly into the bloodstream, and allows the patient to self-administer an extra dose periodically, when needed. This treatment requires an external pump, and is costly and inconvenient. Fortunately, several narcotic medications now have a more convenient dosage form, but still mimic the advantageous continuous infusion characteristic of PCA. Morphine and oxycodone have long acting and short acting formulations which can be combined for effective pain control. Fentanyl is another narcotic which can be administered through the skin with a patch that delivers a constant level of medication for 72 hrs. Fentanyl can also be given in an oral transmucosal form that is rapidly absorbed for quick relief of "breakthrough" pain.
In addition to the narcotics, there are new non-steroidal medications which can be helpful either alone, or in addition to other medications for pain control. Both COX-1 (ibuprofen, naproxen, etc.) and the new COX-2 (celecoxib, rofecoxib) inhibitors play an important role in achieving adequate relief of cancer related pain. Tramadol is another non-narcotic medication that may be used adjunctively to improve the pain control of a narcotic regimen. Other analgesic adjuvants include steroids, tricyclic antidepressants (amitriptyline), and anticonvulsants (gabapentin). Physical therapy, acupuncture, and other non-pharmacologic methods may also be helpful in pain control.
These treatments appear to control pain in about 90% of cancer patients. Research continues on ways to do better!
The primary cause of death in cancer patients is often related to organ failure. However, the consequences of bone marrow suppression may result in serious, sometimes fatal, complications, such as bleeding and infection. In the past, cancer patients were often hospitalized for extended periods to treat infections. Now, many effective antibiotics can be given orally, as outpatients, with convenient once daily dosing. More effective antibiotics for the resistant organisms which develop in cancer patients have also improved our ability to rapidly heal patients with otherwise fatal infections.
Fatigue is a common symptom in cancer patients, either associated with the disease itself or as a side effect of treatment. Chemotherapy occasionally causes anemia which contributes to fatigue. Transfusion of red blood cells can improve the fatigue of chemotherapy related anemia, but transfusions have several drawbacks. Blood for transfusion is in short supply, may carry infections (hepatitis is now much more common than HIV), and may result in serious allergic reactions. The hormone which induces red blood cell production (epoetin alfa) can be administered subcutaneousley once per week, and has been shown to significantly reduce the symptom of fatigue in cancer patients on chemotherapy. A new form of this medication, darbopoietin, has already been approved for use in patients with anemia due to renal failure. Trials of this new agent will soon begin at GBMC in cancer patients. The drug may be equally effective in lower doses or with less frequent administration.
Fatigue may also be related to depression, a symptom which patients often deny. More liberal use of psychiatric medications often help improve mood, and lessen fatigue in cancer patients.
Another frequent consequence of bone marrow suppression is a low white blood count. This complication often limits the amount of chemotherapy which can be given, and this dose reduction could potentially affect the anti-tumor response of the antineoplastic drugs. In addition, low white counts (neutropenia) can increase the risk of serious infections (see "Infection" discussion above).
Two drugs are currently available to treat neutropenia: G-CSF (Neupogen) and GM-CSF (Leukine). These drugs are administered subcutaneously for ten or more days after chemotherapy to rapidly reestablish the normal white blood count. A new pegylated form of G-CSF has been in clinical trials at GBMC. It appears to be equally effective but can be administered in a single injection after each treatment cycle. Studies are continuing, to establish the appropriate role for this new form of an "old" medication.
Loss of appetite (anorexia) is a common problem in cancer patients with metastasis. It results in weight loss and malnourishment, which further stresses bodily functions, and the immune mechanisms required to maintain both quality of life and overall survival. Steroids have long been known to alter various aspects of metabolism and occasionally increase appetite, but steroids also cause significant side effects with long term use. A specific hormonal steroid, progesterone (Megace), has proven helpful to induce weight gain in cancer patients. It can be effectively used with minimal toxicity.
Anorexia may be due in part to the elaboration of a cytokine, Tumor Necrosis Factor (TNF), by the malignant cells. Certain antihypertensive agents appear to inhibit the mechanism through which TNF causes weight loss. One of these agents will soon be available at GBMC through an experimental study for prevention of weight loss in cancer patients.
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