I increasingly came to recognize the field's need for qualified and compassionate professionals, to develop a sense of its challenges and opportunities, and most of all to encounter a sense of its rewards and satisfaction. Starting out committing a few of my O.R. days to the Pain Clinic at the University of Rochester (where I served as Medical Director) the distinction between the impact of a sick day in the O.R., where I could be easily "covered" versus one in Pain Clinic, helped me develop a sense of the degree to which a committed individual could make a difference in the field, which I believe is the principal reason most of us went into medicine.

So, in a sense, it was a matter of the field "picking me." With increased exposure, it became clear that oncologic patients were vulnerable and, other than nursing (physicians' perennial conscience) had very few advocates with respect to pain and symptom control and even dignity. Developing a cancer pain initiative, modeled after the seminal Wisconsin program, was a timely decision since, despite the outgrowth of the U.K. hospice movement, the field was still very much in its infancy and required champions to intervene for patients and their family members. Working to integrate managing pain and other symptoms with the very demanding aspects of treating a life-threatening and potentially life-shortening illness was challenging, especially without penetrating physicians' typically thin skin, I received superb support from Ron Gabel, Rochester's then-Chairman who, in addition to being both a wonderful human and humanitarian, was overcome with the new experience of an Anesthesiology Department's receiving six digit gifts from grateful patients, and a faculty member being honored as the recipient of the Visiting Nurse Association's Physician of the Year Award, which I still count among my greatest achievements. Ron always provided me with excellent counsel and also supported me by providing the time required to edit my seminal text, Cancer Pain (Lippincott, 1993, new edition pending). The field was seductive because, in working with cancer patients who have few secondary gain issues, I came to feel very appreciated and I determined that this was an area I wanted to be identified with and wanted to help move on to the radar screen, again, in large part, because of the paucity of activity in this area 15 years ago. My recruitment by Rich Payne to the University of Texas M.D. Anderson Cancer Center to serve as his Deputy Chief and the Director of the Anesthesiology Pain Programs and Fellowship, and my five years of service there, locked me in as a cancer pain specialist, and I've not looked back. I recently founded the Patt Center for Cancer Pain & Wellness and divide my time between consultation and patient care, and feel blessed by the reduced bureaucratic load and political considerations. While the bulk of my interest remains oncologic pain, about a third of my practice involves chronic pain management, usually with opioids.
Pain.com: How do you deal with the day-in-day-out management of patients with life-threatening illnesses, some of whom are near the end of their lives?

Dr. Patt: It is not uncommon, on those occasions when I find myself in social situations and people find out what I do for a living, that I am asked how I manage to deal with the depression that must accompany working with cancer patients and their families. My experience has been exactly the opposite, and I think that, besides being good at what I do, is much of the reason I've stuck this long. Paradoxically, in some ways, more so than working with chronic pain patients, my work with cancer patients has been very rewarding: providing even small increments in improved quality of life is usually met with considerably greater performance status and a great deal of patient satisfaction. Unlike many chronic pain patients who may be young with difficult issues like disability, relationships and self esteem, and set you up to fail, providing even the willingness to move things in the right direction is met with lasting gratitude. Rather than a depressing job, it has been one that keeps me anxious to start the next days' work and in these ways is really very reinforcing.
Pain.com: Is there a difference between cancer pain and other types of pain? Is cancer pain more intense?

Dr. Patt: Well, I think that it is fair to say that cancer pain is, in many ways, distinct from chronic pain. Having said that doesn't take us very far because even within the field of cancer pain and chronic pain, there is such a very broad range of conditions that relate to the underlying pathology, the meaning of pain, the patient's personal history, and many, many other factors. Yes, I would say that cancer pain is different in some ways and even then it is still comprised of a very heterogeneous group of disorders. It is interesting that the public's perception is that cancer pain must be a very, very severe pain, and one for which we don't have adequate treatments. In fact, cancer pain comes in all shapes and sizes and it is extraordinary the degree to which many of the problems are much more straightforward than they might appear otherwise, once we take the time to sit down with the patient and family, perform a careful history and physical examination, develop a problem list and sort it all out. Cancer pain is, by no means, necessarily more intense or severe than pain associated with other chronic disorders. One of the main distinctions between cancer pain and chronic pain is simply its context. In dealing with many cancer patients, comfort is the highest priority. In dealing with patients who are more likely to live longer or who are at least not at risk for a shortened life on the basis of their disease, it is essential to integrate goals that relate more primarily to function. Of course, even in the most seriously medically ill patient, function and its associated issues that relate to self esteem and control are always very important, independent of the context.

As a specialty, one of the greatest contemporary challenges to acknowledge is that of determining what it is we have learned from our rich experiences with treating cancer pain that we can then apply to broader models of chronic painful disorders. We've learned, for example, that in the absence of a history of dependence on drugs, alcohol and other externals to manage stressful situations, medical exposure to opioids and other substances previously regarded as being highly "addictive" rarely produce new addictive behaviors. While it is difficult to speak in generalities, there are many similarities between cancer and chronic pain management, but one of the truly important distinctions is that of longitudinal context. In treating chronic pain, clinicians should appropriately be considering their long term ramifications: in applying treatment that seems appropriate today, next month and next year, we must address the years and decades of potentially meaningful contributions to society and family relations that follow, as well as the need for patients with chronic painful illnesses to adjust their expectations and lifestyles. While nerve blocks have critical roles in discrete settings, it is often disappointing to me that naive or excessively bottom line-oriented clinicians behave as if, although we can't "cure" diabetes or hypertension, chronic pain can be vanquished if we could only get a needle in the right spot. Whether pain is due to cancer, degenerative, traumatic or other causes, a multimodal approach that relies primarily on medical management is usually what's called for, even when more highly stigmatized but ultimately medically safe therapies like opioids are required.
Pain.com: How else have your experiences with cancer pain influenced your approaches to chronic pain management?

Dr. Patt: One of the less well understood but essential distinctions that cries to be addressed in managing cancer pain is that between pain directly due to tumors and their progression or recurrence, and chronic pain that occurs as a consequence of cancer treatment.

Many patients (up to 1/3 in some series) with what appears to be cancer pain, in fact, have pain that is entirely unrelated to their tumor, but which may not be relayed because patients are in denial, presuming that more pain signals progression or recurrence. There is no way to administer the most powerful, potentially life-saving or extending cancer therapies without the risk of injuring healthy tissues while trying to kill cancer cells. Such syndromes include post surgical pain, especially after mastectomy, thoracotomy, and radical neck dissection. Surveys have shown that up to 70% of patients after breast surgery, even lumpectomy, will have disabling chronic pain that often goes unrecognized. Pain may persist for years after chemotherapy, usually from damage to small nerves (peripheral neuropathy), but some newer chemotherapy agents appear to produce arthralgias and myalgias (joint and muscle pain) that can be very persistent. Painful complications of radiotherapy, administered even in the most expert of centers, can produce bone necrosis and soft tissue scarring that can be quite problematic, hence the good news, bad news conundrum, that we have (maybe) cured your cancer, but likewise may produce lifelong disabilities. The pain observed in long-term cancer-free survivors resembles other chronic pain syndromes in important ways. It is both a critically fertile field for study and has taught us a great deal about the safety and usual stability associated with truly chronic opioid use. Working in a large cancer center, one of my earliest observations related to the presence of this large cadre of cancer survivors: individuals no longer directly threatened by their neoplasm, but in whom stable chronic pain persisted. Despite toxic chemotherapy, ionizing radiation and severing intercostal nerves, rotating flaps and fusing vertebrae, even the most dedicated and compassionate surgeon or oncologist would usually tire of or would question prescribing regulated substances months, years, and decades after incisions have healed. Using a combination of sequential trials of adjuvant analgesics and low dose opioid maintenance, I was fascinated to observe that the vast majority of such patients, after an initial period of titration to effect, would maintain comfort on stable doses, literally for years and even decades, and that if doses suddenly escalated, it was usually a sign of recurrence, a new vertebral collapse or some other painful event. For me, this was palpable proof that the concept of "galloping tolerance" was mythic: that once the "dangerous" threshold of prescribing opioids was crossed, the clinician would inevitably tumble down a slippery slope leading to industrial strength doses and loss of control. I don't mean to intimate that drug abuse, drug diversion and the medical need for titration to "high" doses don't sometimes occur, but as data that I will soon publish will substantiate, these difficult but usually manageable scenarios clearly represent the exception and not the rule. My usually, but not always, elderly cancer survivors wearing 25 or 50 ug/hr transdermal fentanyl or 15 or 30 mg of controlled release morphine twice daily were not breaking into convenience stores or engaging in other aberrant behaviors classically associated with addiction to satisfy an ever-increasing drug hunger. In the vast majority of patients, behaviors of this ilk appear to be much more closely related to a tight-fisted approach to prescribing than the characteristics we ascribe to these substances. It degrades the human spirit to prescribe from the viewpoint that opioids and similar agents are invested with "magic" powers sufficient to dramatically alter the values and coping styles of individuals who have often lived longer than their prescribing doctors. People, and their ingrained styles of coping, appear to be much more "addictive" than substances, in and of themselves.
Pain.com: What about the side effects of anticancer therapy and how pain treatment and cancer treatment interact with each other?

Dr. Patt: Given the high stakes goals of treating cancer, preserving and extending life, it is not surprising that the risks are significant. The usual goal of chemotherapys is to "push the dose" to as close to toxic levels as can be tolerated to achieve the best tumoricidal effect possible, thus avoiding the risk of going back again.

Even in the most frail of patients, pain and cancer can almost always be treated safely and effectively in a complementary fashion. Of course, denial is rampant and it is common to "shoot the messenger," making it easier to blame the pain medication or chemotherapy than to acknowledge the presence of advancing disease. Interestingly, although we are often accused of shortening life by treating pain proactively, my experience is that the opposite effect is much more common: in addition to effects on quality of life, good pain and symptom control is more likely to extend survival.

In order to manage cancer pain effectively and safely, particularly in patients with active disease, the pain specialist must recognize that many individuals are medically fragile, are receiving polypharmacy for various reasons, and are at risk for complications of treatment. The modes of pain and symptom control need to be selected judiciously and there should be a low threshold for adjusting treatment to "hit a moving target" especially when cancer is progressive or at least in flux. Thus, when effective and tolerated, treatments that can be titrated (turned up, down and off) are often more appropriate than the typically more transient or fixed results of nerve blocks where "what you see is what you get."

It is also essential that pain specialists and oncologists communicate effectively with each other, in order to fully appreciate what each has to bring to the table. The pain specialist must familiarize themselves with the most important potential oncologic emergencies and medical disorders that are common in cancer patients. While they needn't know the latest treatment algorithm for hypercalcemia, recognizing its signs and symptoms will go a long way to earning an oncologist's respect. That would heighten our concern and cause us to dialogue more closely with cancer specialists. Conversely, like it or not, in many communities anesthesiologists are still living down the "cowboy" days when we were isolated in the O.R., treated out of the Recovery Room, and were not available on nights or weekends to deal with the problems that are unique to treatments we provide. Much of this has changed, and ultimately the committed anesthesiologist is in the enviable position of potentially providing the pharmacotherapy expertise offered by other specialists, as well as the more invasive approaches, when indicated. By the same token, although usually by default, oncologists have become among the nation's best pain specialists, even though they never signed on for the job or necessarily received specific training. Someone other than nurses had to step up to the plate, and ultimately medical oncologists, radiation oncologists and the like are on the front lines, and their skill levels have increased dramatically. Anesthesiologists often bemoan how closely oncologists guard their patients. Much of this relates to how busy medical practice is, the cancer patient's medical and psychological vulnerability and the need for both groups of specialists to understand the issues that arise when treating both pain and cancer in the same person.
Pain.com: What about over-the-counter drugs? Are there some you should consider or that you cannot take that may react negatively with radiation or chemotherapy?

Dr. Patt: While there is a potential role for over-the-counter medications in all settings, patients need to recognize that these are indeed medications, and thus can potentially interact with their cancer, pain and their treatment. Also, while we used to believe this to be more a phenomena in developing nations, we now recognize that there is a great deal of interest in the United States in "alternative" and herbal medications and folk therapies. It is essential that the patient not feel ashamed of considering their use, and that their physician be made aware because, even if derived from natural products, these are medications that, like any other, have the potential to do harm and to interact with others. There is considerable controversy about the fact that most of these agents, some of which appear to have considerable value, have escaped the scrutiny of the F.D.A. which is charged with ascertaining that treatments are safe, claims are accurate and which also collects and disseminates data on adverse effects.

Specifically, the currently available over-the-counter anti-inflammatory drugs like naprosyn, ibuprofen, ketoprofen and aspirin (all of which are marketed under various names) should not be used at the same time as corticosteroids (which are commonly used in anti-emetic regimens and in anti-cancer therapies) because of the added risk of gastric complications of bleeding and ulcerations. Likewise, most of the anti-inflammatories, even over the counter, thin the blood excessively in patients on chemotherapy agents that depress bone marrow function. So it is essential that the patient give and the health care team get a full history and that patients are aware that, even though some of these treatments have potential value, they are medications and their doctors need to know they are taking them.

One of the issues that arises increasingly in contemporary practice involves the mutual responsibility of the doctor to ask and the patient to volunteer all pertinent information. The need for this attention to detail, the time for which is increasingly hard to find as we are all asked to do more with less, is typified by how we regard the use of over-the-counter laxatives.

One of the founders of the modern hospice movement in the United Kingdom, has said "the three most important things about palliative care are the bowels, the bowels, and the bowels." Because we are very busy practitioners and because in our culture, bowel habit is regarded as a personal issue that patients can self-regulate, we often fail to regularly obtain a good history. Patients with altered diet and activity who are taking multiple medications that slow bowel transit are often not given good medical advice about the need to manage the bowels proactively. Thus something that sounds as low key and trivial as obtaining a good bowel history can be extremely helpful in terms of easing distress and confusion, reducing nausea and preventing emergency admissions. One only really need to be at either end of a manual disimpaction once to be motivated to avoid repetition. Although partially controlled trials suggest that transdermal fentanyl may be less constipating than morphine, it is a sine qua non that all patients on opioids will usually need preventative laxative therapy, usually with a sliding scale dose of a combination mild softener and stimulant, and a stronger, usually osmotic agent like lactulose for "breakthrough" constipation.

This example speaks to the need to address what may appear to be relatively minor aspects of treatment that can make a great deal of difference to patients' well being.
Pain.com: What are the primary concerns of cancer patients? Do they worry about addiction or side effects?

Dr. Patt: Patients' concerns are quite variable. Patients as well as clinicians maintain antiquated concerns about these issues. When threatened by cancer, patients are open to relearning what they thought was true about analgesics, but this can occur only when health care providers send clear messages about drug safety. Older surveys suggest that cancer specialists didn't used to believe that pain was a very common or serious problem. That relates largely to the fact that patients were very reluctant to talk to their doctors about pain.
Pain.com: Even excruciating pain?

Dr. Patt: Even excruciating pain. Much of it relates to the fear. There is societal pressure, patient concern about addiction, side effects, and the appearance of being drug-seeking. Patients recognize that the physician's allotted time with them is modest and they do not want to take time away from issues that may directly relate to their survival.

Far from being an excuse for undertreatment, patient reluctance to talk about pain actually increases our mandate to ask about pain. Although, after survival, pain is probably patients' second most important concern, it often is not addressed and creates a special obligation on health care providers to begin that conversation. If we wait for it to happen, it will often only occur once severe pain is already well established and much harder to address and treat effectively.
Pain.com: Are there ways to reduce pain, nausea, and some of the side effects that come from some of the therapies that are being administered?

Dr. Patt: Yes. There are very effective ways to address pain and symptoms related to cancer treatment and to cancer progression, even in the most grim of situations. In fact, that is what is so rewarding about working with symptomatic cancer patients, although it is time-intensive, with nothing much more high-tech than a pen and a prescription pad, probably 70-90% of cancer patients' pain and related symptoms can be effectively treated in a durable fashion. Those outcomes are very, very good in a cancer population. Because, at least until recently, there has really been no individual or set of individuals held accountable for addressing pain and other symptoms, they were often managed poorly, if at all. We once assumed that pain was an inevitable component of cancer, especially progressive cancer. We began to learn much more about this as the World Health Organization fulfilled its charge to address the public health of individuals in developing countries. Recognizing that in areas where physicians are in poor or remote supply, patients typically see doctors after their disease has progressed beyond the potential for cure, providing more chemotherapy or radiation centers, at least in isolation, would not have the same effect as attention to early detection, life-style modification, and palliative and supportive care. While not a very well-funded organization, The World Health Organization is at least highly prestigious, and its endorsement of investigations into low-tech means of providing pain and symptom control in rural, developing areas helped a great deal. They found that using the simplest of prototype drugs (aspirin, codeine, and morphine), a durable treatment response occurred in 70-90% of patients, independent of the practice setting. We have come to recognize that the same methods are at least as effective here, although given the availability of new drugs, new delivery methods, and routes of administration, they are usually applied in a more sophisticated manner. With the availability of "medium-tech" and "high-tech" interventions, the cancer patient who experiences persistent, severe pain should truly be the rare exception. While patients' right to pain relief is arguable, their right to our best efforts to provide it should be inalienable, and ideally, cancer patients should never hope for an early death by means of physician-assisted suicide or euthanasia because their pain and symptoms are not adequately addressed.
Pain.com: Let's talk a little bit about opioids. There are a lot of controversies surrounding the use of opioids for non-terminal pain, albeit cancer pain or any other kind. What are your thoughts on that subject?

Dr. Patt: When I initially got involved in treating pain I was enthusiastic to the point of being evangelical about spreading the good word of how effective these medications and related therapies were for treating cancer pain. There are now many more cancer pain experts, and it would be a very unpopular position today to advocate for the less liberal treatment of pain in patient's with life-threatening diseases.

The really exciting challenge in contemporary pain medicine is for us to look honestly at what we have learned from this very rich (both in depth and breadth) experience of treating cancer patients, and determine what it is that we can begin to translate to larger populations of patients with chronic painful medical disorders.

Historically ingrained misinformation had led to the expectation that many of our cancer patients would become addicted. Originating mostly in the United Kingdom, there was a courageous recognition that even if this were so, it may be a more desirable alternative to die addicted but comfortable than to experience the indignity of unrelieved pain at the end of life, or at least that patients should have a part in choosing among these options. I think it was only in retrospect, and certainly to the surprise of many, that we learned that addiction, as contemporarily regarded, is in fact a very rare outcome of medical treatment with opioids. This data is derived from surveys performed in populations of > 10,000 patients who have received opioids for the treatment of burns, postoperative pain, and cancer pain. These surveys suggest that, in the absence of a history of substance abuse, less than 1% of patients given opioids in a medical setting will experience problems related to addiction. Even if these studies are not entirely reliable, and the risk is as great as 1 or 2 or even 5%, this is a recognizable and treatable complication that should not prevent the other 90-odd per cent of patients from being treated. So one of the lessons from cancer pain is that addiction is a rare phenomena, and this pointedly raises the question of why opioids should not be considered more regularly for patients with other models of chronically painful medical disorders. The main difference is that our chronic pain patients are more likely to live a longer lifespan, and their functional status becomes more of an issue. Opioids have been used successfully in cancer survivors for decades, and can actually enhance function in the presence of chronic pain, with little risk of addiction.
Pain.com: Are opioids the only things that will quell intense cancer pain?

Dr. Patt: No, but they are generally regarded as the mainstay of treatment. There are many therapies that have potential value, often administered concomitantly. This emphasizes the need for a good assessment of the nature of the pain as well as the psychosocial and environmental factors that are contributing to it, and the nature of the underlying disease.

So, in the case of cancer, primary antitumor therapies will ideally, in the long term, modify pain by modifying the tumor's architecture and biologic behavior. So, shrinking or removing tumors with surgery, radiotherapy, or chemotherapy, when appropriate, is often associated with pain relief. Since all of those treatments have limitations and toxicities, we often rely on treatment with analgesics including the opioids, as well as interventional procedures as might be performed by anesthesiologists and neurosurgeons to modify the way pain is transmitted.

One of the most important contemporary advances is the recognition that these strategies can and should be administered in a complimentary fashion. You don't just treat the tumor, waiting for a pain response, and then use analgesics only if it doesn't occur. In the case of a painful bone metastasis treated with radiotherapy or radioisotope, it is very important to use medications to treat the pain while awaiting the three to six weeks that may elapse for a treatment response from the anti-tumor therapy.
Pain.com: Does everybody who has cancer experience pain?

Dr. Patt: Everyone who has cancer, as well as those who are close to them, suffer and experience distress. Suffering and distress, depending on how you interpret the meaning of the words, are a bit like pain. With respect to pain as a more discrete event, it is one of the more common symptoms, occurring overall in about 2/3rds of patients, probably in 80-90% of patients with advanced cancer, and in up to one third of patients, with early and intermediate stage cancer. Pain in patients with early and intermediate stage disease has been less well characterized, in part because patients who are recently diagnosed with cancer are often so very focused on getting the best cancer treatment, that they may be reluctant to report pain.

The reluctance of those with earlier stages of disease to report pain, emphasizes our need to ask about pain, especially since, in addition to its obvious effects on quality of life, there is mounting evidence that untreated pain interacts with survival as well. Cancer patients who do not avail themselves of good pain treatment may be at greater risk of succumbing to their cancer. We are beginning to understand that treating pain and symptoms is very closely tied to cancer treatment. There are powerful indirect links that relate to compliance and performance status: it is hard for patients with pain to follow what are often demanding recommendations for anti-tumor therapy, and likewise, those with pain and poor performance status are often not offered investigational therapies. There are also increasing cues for direct immunologic and other physiologic links between symptom management and survival.
Pain.com: Is the medical community divided on the proper methods to alleviate pain?

Dr. Patt: There is certainly less concern today about treating the patient with active cancer, and as I have indicated, our real challenge relates to demystifying opioid therapy for the ongoing management of patients with chronic pain and a long life expectancy.

Even in the setting of cancer, there is controversy about how to treat cancer survivors who, although cancer free, have pain of a long-standing nature related to their cancer treatment. A large and growing contingent of oncologists and pain specialists have recognized that pain due to surgery, chemo-, and radiotherapy can be managed effectively for years without addictive behavior or impairment. Treatment often involves "strong" analgesics, usually administered around-the-clock by a simple route of administration that maintains independence (orally, transdermally and, more recently, transmucosally), and thus there remains, in many quarters a reluctance to continue to provide longitudinal treatment once the direct and immediate threats of cancer are resolved.

Even in the presence of active tumor progression, these concerns about addiction and side effects are so deeply rooted that they can arise when least expected. One of the main bones of contention relates to the fact that in using the opioid drugs, it is now recognized that there is no ideal dose that will work for everyone, all the time. The principle of treating pain with opioids is much more akin to how we treat diabetes than how we treat an infection. This is hard for doctors who are scientific, and like to be able to go to a textbook and get an answer that works for everyone of a particular kilogram weight or body surface area. In the case of an infection, we can go to a book and, for a given bug, identify a drug of choice, dose of choice, an interval between administrations of choice, and duration of therapy of choice. In the case of diabetes, the treatment model for which is much more like that of cancer pain, how do we arrive at the correct insulin dose? There is no "best dose" of insulin. We give insulin until the blood sugar returns to a controlled level and if it starts to dip, we reduce the dose. The same is true in treating pain with opioids except we don't have a blood test to help guide our treatment. It requires that we have relationships with our patients and that we ask them about their pain and that we have a willingness to believe what they tell us about their pain. So, the construct in dosing opioids, and I think this is very much at the heart of the controversy about treatment, is that you usually start at a low dose because you want to try to avoid side effects whenever you can. You gradually increase the dose until you either get the effect (comfort, analgesia, pain relief) or prematurely encounter a side effect, in which case you institute an algorithm for treating the side effect, manage that, and then get on with the titration to effect. The "best dose" is the dose that works in a given patient, and for one patient it may be 1 mg and in another patient it may be 1 g. This is a model that has been difficult for us to adapt to.
Pain.com: Where do you see the immediate future going with the development of new drugs and therapies in dealing with cancer?

Dr. Patt: Unfortunately, what is most exciting is most easily overlooked: the more effective use of drugs that have been available in one form or another for several hundred years. Today's armamentarium features a greater breadth of choice and customized delivery systems that ensure durable, effective treatment for most patients with a low incidence of largely manageable side effects. What is needed for treating cancer, and by extension, chronic pain, optimally involves a reconsideration of our priorities, our regarding these medications in a different way, and a willingness to address pain in the same fashion that we would a cardiovascular or gastrointestinal complaint, rather than regarding it as a primarily psychological disorder. While it is certainly true that pain always has psychological features and that pre-existing psychological problems sometimes influence pain, these are all certainly worsened by under recognition and undertreatment.

To sum up, then, the first step in relieving a great deal of suffering involves using what is already at our disposal more effectively. The best testimony to this premise is that many of the exciting developments over the last decade, relate to using old drugs in new packages. Familiar drugs like morphine and oxycodone are available in controlled release tablets and capsules that, when used regularly, provide relief for 8-24 hrs. Such treatment avoids the "roller coaster" effect of postponing medication use until pain is excruciating and ensures a happier and more compliant patient. In appropriate settings, this advantage can be extended to 72 hr by using a skin patch for drug delivery. We now recognize, for example, that fentanyl, a strong narcotic or opioid, that was conventionally used only by injection, especially by anesthesiologists, is effective over the long term by teaming it up with a sophisticated transdermal (skin patch) delivery system, and because it is so strong, we simply administer it in micrograms rather than milligrams. Putting a slightly different spin on this advance, a new lozenge-based preparation of fentanyl has recently been approved for breakthrough pain in cancer patients. Most experience meaningful pain relief within 5-10 minutes of beginning to consume a fentanyl lozenge or oralette because, in addition to some drug being swallowed, it is rapidly absorbed across the oral mucosa, which is a highly vascular organ.

The second part of the answer to this question, further relates to new twists on old remedies and involves developments related to new drug receptor-related discoveries. While the successful design of an opioid that works specifically at receptor subtypes that discretely mediates pain relief without side effects has so far eluded us, we have been more fortunate in other areas. The best example may be that of the anti-inflammatories (NSAIDs). We are in the midst of bearing witness to the introduction of hordes of more specific agents, termed "COX-2 inhibitors." Classic NSAIDs (ibuprofen, naprosyn, etc) work by inhibiting the enzyme cyclo-oxygenase (prostaglandin synthetase), predominantly at the COX-1 receptor, and as a result, in addition to relieving pain and inflammation they are associated with a myriad of potential side effects, especially related to the GI system and "thinning" of the blood. While these newer "COX-2" inhibiting agents, the first of which, celecoxib (Celebrex), is already available, and the second of which, rofecoxib (Vioxx), has been approved, appear to be about as effective in reducing inflammation and pain, they appear to do so very safely, with much less risk of stomach ulceration, bleeding, and other side effects. Even with careful FDA scrutiny, there is no way to entirely understand the toxicity story until after approval, once hundreds of thousands of patients have been exposed. Nevertheless, this particular group of drugs appears to be both safe, and may have additional other important roles such as that of reducing the risk of colon cancer (chemoprevention), for example. With respect to pain and inflammation, there is a good chance over the next few years, this new chemical class of NSAIDs will entirely supplant the drugs that we have come to rely on for the last several decades.

A similar discovery that has modified current thought relates to the recognition that antagonism of the N-methyl-D-aspartate (NMDA) receptor may play an important role in the relief of neuropathic pain and, perhaps, the regulation of tolerance. Although dextromethorphan, one of the active ingredients in over-the-counter cough syrups acts at this site, its use is impractical, as is the widespread use of ketamine, an anesthetic agent with a significant side effect profile. While both methadone and dextropropoxyphene have NMDA receptor antagonist activity (as, incidentally does magnesium), their use is complicated by the potential for accumulation in the former and low potency in the latter. Another molecule, however, dexmetatomadine, has been successfully combined with various venerable opioids like morphine, hydrocodone and oxycodone. A fixed combination of this NMDA receptor antagonist and morphine has fared well in multicenter clinical trials, suggesting that a "more efficient morphine" will soon be available. This and similar "drug marriages" promise a different way of using old drugs more effectively.

So, the goal is to hit this moving target of pain more accurately, staying in the therapeutic window that is associated with an acceptable balance of comfort and side effects, and avoiding both the risk of increased drug abuse and the specter of exaggerated concern over drug abuse. Even with these and other new molecules, drug, devices and paradigms in the pipeline to advance these goals, savvy, committed savvy are ultimately the key to using these tools effectively.
Pain.com: It is understood that oncologists may be reluctant to seek help from pain specialists. Are oncologists sufficiently trained to deal with pain, or should a patient consult a pain specialist?

Dr. Patt: Ironically, mostly by default, oncologists rank among our nations' best pain specialists. This is true despite the fact that they never "signed up for the job," or necessarily received any formal training. Historically, and even in contemporary practice, despite a high rate of exposure to patients with pain, neither oncologists nor most primary care providers or specialists typically receive adequate training or an adequate orientation to manage pain effectively. In virtue of their front line status, especially in a context where undertreatment is the norm, oncologists and the nurses, pharmacists and other therapists that comprise their team have become generally very good at treating pain for most patients using straight forward treatment approaches.

I would expect that in most communities, today's patients have a reasonable likelihood of receiving acceptable treatment for their pain from a cancer specialist. In the United States there has been a parallel effort, both to (1) empower primary care providers and oncologists to meet their obligations to treat straight forward pain problems with straight forward therapies, including the sophisticated use of controlled substances, and (2) to establish pain management as a legitimate medical subspecialty, for those patients who will not respond to such measures and require either expert consultation or specialized techniques.

Ultimately, a proportion of patients will have pain that is difficult to manage, whether due to cancer or other causes, and in addition, a proportion of oncologists and other providers will lack sufficient training, orientation, or motivation to address pain effectively.

While it is important not to trivialize the need to identify, assess and manage cancer pain effectively, the therapies that are usually most helpful are disarmingly straight forward. The main needed commodities are (1) a motivated, cooperative patient, (2) a committed health care provider with basic, easily attainable skills, (3) a healthy dose of common sense, an unfortunately uncommon commodity, (4) good communication skills, and (5) attention to detail. I don't want to be disingenuous: while providing good pain and symptom control for most patients is achievable, it is a time-intensive endeavor, especially at discrete time periods like the beginning of treatment, when conditions change and if death approaches.

There is most certainly a proportion of patients who are likely to benefit from a referral for specialist consultation. There is increasing evidence that many such patients can be identified prospectively when specific prognosticators exist, including a history of alcohol or drug abuse, mood disorders including depression and anxiety, the presence of delirium, cognitive dysfunction, tolerance, neuropathic pain and pain associated with movement.

Likewise, in a health care delivery system dominated by healthy, young, white males, females, minorities, and geriatric and pediatric patients are more likely to be undertreated and under-referred. It is a multifactorial problem, as patients are often protective of physicians who care for them, often minimizing their symptoms so we are not discouraged. In the context of the many overwhelming aspects of being diagnosed with cancer, these considerations combined with the stigma associated with even the medical use of drugs make it the rare patient who is willing to confront our white coats and say, "I'm not satisfied with my current level of pain control...do you think I would benefit from a second opinion or a specialist's help?"

There is every reason to expect that oncologists, anesthesiologists, palliative care experts and others can communicate together effectively on the patient's behalf. Regrettably, today's health care environment requires that patients be careful and assertive health care consumers, no mean feat at the moment in our lives when we are most vulnerable and already using all available resources to survive. There are increasing resources available today on the Internet and from professional societies, pharmaceutical companies and governmental agencies that assist patients in achieving at least our best efforts at relieving pain. It is less a matter of patient entitlement to freedom from pain, as it is their right for our best efforts to achieve pain control. Further, even when there is a shift in focus because antitumor treatment is inappropriate, the intensity should persist and a suffering cancer patient should never hear "there is nothing more I can do." This philosophy, together with a focus on life style modification, early detection and even bereavement is what optimally constitutes comprehensive cancer care. The efforts of committed professionals to combat cancer pain are usually very successful, although still undermined by exaggerated concerns about addiction, drug diversion and regulatory reprisal. Today's patients with cancer pain and especially those with other chronic painful disorders remain innocent hostages of a war on drug abuse which, while appropriate, is unrelated, except insofar as we fail to make these distinctions.
Pain.com: It is always interesting to bring these things to a personal level. If, heaven forbid, you were a victim of cancer, how would you want to be treated and what kind of medications would you want to receive? I know it depends upon the kind of cancer, but in the hypothetical...

Dr. Patt: I would first of all say that one of the gifts extended to me by my patients with cancer is a recognition of the value of our health and pain-free days, and a recognition that we do not live forever. Something will appear on the radar screen for us or our families at some unexpected time in our lives.

If I were to experience a malignant disease associated with pain, I would want to have one physician that I could rely on as a coach or team captain, accountable for my wellness overall, someone, who might or might not be the same person, charged with looking after symptom control, and a mechanism in place to ensure that these multiple specialists communicate effectively to each other.

I recognize that pain is a moving target, and I would like its treatment to be as plastic and dynamic as the pain, depending on the underlying disease and a lot of other features. I would opt, generally, for the best practice of medicine, or the art of medicine, which is the safest, most straight forward treatment that has the greatest potential to help without producing serious and lasting side effects. To the degree that I have influence, and I hope that I would, first opt for sequential trials of analgesics given by convenient and uncomplicated routes. Given what is available today, if the pain was significant, I would expect the need for opioid analgesics, perhaps transdermally or orally, with oral or transmucosal agents for breakthrough pain. With titration to effect and surveillance for side effects, I would anticipate a likelihood of good pain control, at least during periods of stable disease. If pain or side effects persisted, and I think we are not as attentive to identifying side effects as we might be, I would expect the consideration of a trial of stimulants, an under-prescribed and highly stigmatized class of drugs, like Ritalin, for maintenance of alertness. Should such measures be ineffective, I would probably opt for spinal or intracerebral drug delivery to reduce drug burden and side effects, and would hope for a convenient, internalized delivery system that would not interfere with my independence. For very discrete, well-localized pain, I would consider the judicious use of nerve blocks, but given the dynamic nature of cancer pain, treatment would ideally be of the type that can be turned up, down and off. Most importantly, I would hope to gracefully assume the role of an educated health care consumer who remains involved in the decisions that have such impact on my self and my family.
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