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Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Holland-Frei Cancer Medicine. 5th edition. Hamilton (ON): BC Decker; 2000.

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Holland-Frei Cancer Medicine. 5th edition.

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Chapter 37Principles of Medical Oncology

, MD, , MD, , MD, and , MD.

A medical oncologist is an internist who has undergone additional specialized training. A good medical oncologist is one who applies the thoughtful approach to problem solving he learned as an internist to a body of knowledge that includes patients with cancer. Specific features about individual cancers and their treatments and a reasonable familiarity with the origins, status, and fruits of cancer research at clinical and preclinical levels are requisite. 1 More than in many internal medicine specialties, a medical oncologist interacts with cognate brother and sister disciplines, particularly surgical oncology, radiation oncology, and pathology. Multiple other interactions occur with nursing oncology, diagnostic radiology, psycho-oncology, neuro-oncology, gynecologic oncology, rehabilitation medicine, and, for young patients, pediatric oncology. Infectious diseases are common complications of cancers and their treatments, and the parallelism between use of antibiotics and chemotherapeutic agents forges a natural alliance with specialists in infectious diseases.

The relationship of medical oncology to hematology is special. Medical oncologists and hematologists both have legitimate interests in neoplastic diseases of the hematopoietic tissues (1) because of the commonality with other neoplasms, and (2) because of the organ system involved. There is a large segment of hematology which is not uniquely related to oncology, however, and the major segment of oncology is not in the province of hematology.

Medical oncology was established as a separate discipline by the American Board of Internal Medicine in 1971. More than 15,000 certified internists have been further certified by the Board in the subspecialty of medical oncology. From time to time, since 1971, efforts have been made by others to join medical oncology and hematology together. The content and orientation of the two subspecialties allow joint training and coexistence, but the authors are disinclined to consolidation. This reticence reflects (1) the National Cancer Institute’s separate identity from the National Heart, Lung, and Blood Institute; (2) research in a far broader field than just hematology; and (3) the oncology practice’s patient mix, which involves more than 80% of patients with diseases that arise from and affect other body systems. Although many topics and training programs elicit interests in common, the allocation of time to the two disciplines should not necessarily be equal in those institutions that choose to maintain combined training programs. A separate hematology training track should be available to those whose interests do not focus on neoplasia; a separate medical oncology track should be available to those whose interests are primarily in cancer. 1

The Medical Oncologist’s Role

A medical oncologist must understand the pathophysiology of cancers of different sites. All cancers are not identical, and all patients who have cancer are not doomed. Indeed, many patients live with cancer, and given the present state of our knowledge, many will have to do so until they die. Having cancer is not the same as having a cancer that will kill you, and not a few patients have a neoplastic disease which is relatively less important to their overall health than their cardiovascular disease or some other affliction. Faced with a diagnostic problem, oncologists must try to exclude cancer as the cause. Many other diseases can mimic cancer, but in the endeavor not to miss a nonmalignant disease, the internist and the medical oncologist must remember that cancer can “do anything” and, thus, must be considered in every differential diagnosis. Cancer has replaced syphilis as the great imitator. 2 To ascribe a finding to cancer requires histologic proof on at least one occasion. For complex new syndromes appearing in a patient who once had cancer, such as pulmonary insufficiency, meningoencephalopathy, or inexplicable pain, it is indispensable to establish by objective criteria that cancer is the proximate cause. Cancer patients are not protected from other symptomatic benign diseases, such as pulmonary fibrosis, central nervous system diseases, or painful conditions, such as herniated disc. No symptom should be attributed to cancer without persuasive evidence. Yet cancer must be suspected every time.

For the patient in whom relatively asymptomatic findings lead to a diagnosis of cancer, it is useful to consider that the day before the discovery, the patient was living with cancer. It is a source of some encouragement to patients to know that a diagnosis of cancer does not lead immediately nor inevitably to the end of life. The medical oncologist may be able to stress the long-term evolution of a cancer, the several stages which intervene between the carcinogenic stimulus, the mutation at a genetic level, the progressive selection of cells with a survival advantage, and the appearance of an autonomous neoplasm. Since this process usually takes years, and often decades, it is of value to place the neoplastic process in perspective.

The medical oncologist must distinguish between a neoplasm where a chance for cure exists with known information, where a chance for cure is possible in the context of current and ongoing research, or where our present ignorance precludes that likelihood. In this context, tumors can be classified therapeutically as curable and precurable (Table 37.1).

Table 37.1. Classification of Tumors By Chemotherapeutic Effects*.

Table 37.1

Classification of Tumors By Chemotherapeutic Effects*.

There are probably few incurable tumors; the present state of our knowledge and the primitiveness of our tools just obscures the proper approach to achieving cure. 3 It is axiomatic that the day before the first metastatic choriocarcinoma was cured with high-dose methotrexate, 4, 5 metastatic cancer, in general, was considered incurable by most observers. Similar considerations apply to every neoplastic disease that is now curable (Table 37.2). Other neoplasms are “subcurable” by chemotherapy, insofar as the participation of surgery or radiotherapy is an intrinsic part of the therapeutic process (Table 37.3).

Table 37.2. Chemotherapeutically Curable Cancers*.

Table 37.2

Chemotherapeutically Curable Cancers*.

Table 37.3. Cancers Subcurable with Chemotherapy*.

Table 37.3

Cancers Subcurable with Chemotherapy*.

The next place where dramatic change may become apparent is as unpredictable as was the response of choriocarcinoma to methotrexate or testicular cancer to cisplatin. Old algorithms may fail, but new approaches and new drugs could provide dramatic opportunity for significant advances (Table 37.4).

Table 37.4. Discoveries That Could Lead to Major Advances in Cancer Therapy.

Table 37.4

Discoveries That Could Lead to Major Advances in Cancer Therapy.

Clinical Responsibilities

The medical oncologist is often involved in the final decisions concerning management and is frequently the final common pathway through which decisions are implemented. The timing of surgery and radiotherapy, the decision on whether to take curative or palliative approaches, and the decision whether watchful waiting is the appropriate approach or if vigorous action is necessary are often entrusted to the medical oncologist by the patient. He or she must have knowledge of the natural history of a disease so as to conceptualize the likely future and its optimal organization for a specific patient. In addition to a personal library, selected reprints, and access to computer databases, a medical oncologist is well advised to construct a database of patients seen. Not a few of the editors now wish they could recount the precise details of yesterday’s remembered patients from whom we learned and whose cases are relevant to today’s problem.

Patients are often influenced by their present state of subjective well being. It is the responsibility of an oncologist to recognize the often pernicious behavior of cancer in its potential for recurrence and metastasis. In this context, the medical oncologist must interact directly with the patient as well as with the chart, films, slides, and other critical raw data. Only in such a fashion can advice be tendered with commitment and with the expectation that the patient can be guided to a proper choice. It is unrealistic to expect a patient with a neoplasm to make a choice (informed consent) that is dispassionate, since the very fact of having cancer constitutes a serious emotional burden that may distort ordinary reason. By firsthand intimacy with the diagnosis, the extent of the disease, and the patient’s attitudes and infirmities, the medical oncologist can make rational recommendations to the patient and to the other physicians involved.

Many of the other physicians who are involved with a particular patient may concentrate in fields other than surgical or radiation oncology. It is not uncommon, indeed it is often the case, that the patient has a primary family physician or internist who referred the patient to a medical oncologist. In some circumstances, cardiologic, pulmonary, neurologic, or other specialists may already have been involved with the patient prior to the recognition of a neoplastic disease. It is incumbent upon the medical oncologist to recognize their interest and their continuing role in the management of patients with multi-system disease. An infectious disease specialist often becomes involved. In the absence of such consultants, however, the medical oncologist must also implement all aspects of internal medicine. Elsewhere, this book contains detailed descriptions of various diseases, the modalities used in their treatment, the pharmacologic, immunologic, neurologic, psychologic, biochemical, epidemiologic, and molecular biologic aspects of cancers, and the complications that cancers cause. Oncologic emergencies, rehabilitation, and the oncologist’s relationship to medical informatics and to government are also presented. Familiarity with these topics constitutes a foundation for medical oncology from which the principles derive.

Cancer Prevention

Medical oncologists—because of their knowledge of neoplastic disease and because of their recognition of social, occupational, nutritional, and sexual practices that contribute to neoplasia—have a special obligation among physicians to educate the general public, including other professionals with a less intense interest in cancer prevention. Smoking is the principal correctable cancer-inducing activity. Medical oncologists should not smoke. Medical oncologists should counsel patients and families about good nutrition and healthy sexual practices. Several chapters of this treatise deal with prevention, and numerous publications that deal with cancer prevention are available for distribution to patients and families from the National Cancer Institute and the American Cancer Society. The Cancer Information Service (1-800-4-CANCER) will send available publications free of charge.

Familiarity with genetic predispositions to cancer is essential. Many family members immediately fear for their own safety when a relative is diagnosed with a neoplasm. This is entirely appropriate for conditions known to be associated with a genetic predisposition, but not for all types of cancer. It is usually the medical oncologist’s responsibility to assess the risk for a particular disease and to conduct the necessary surveillance.

Clinical Research

No cancer is so well treated that an improvement in outcome or therapeutic approach cannot readily be imagined. Thus, research is imperative. Furthermore, therapies that allow preservation of the involved organ are much to be desired, and investigations that have led, in many patients, to breast preservation, limb salvage, bladder conservation, and avoidance of abdominoperineal resection are major dividends in the treatment of cancers in these organs. Although in these instances it would appear self-evident, measuring the quality of life is now quantitatively valid and has added a major opportunity to reach value judgments.

Every established paradigm of medical oncologic management arose from some investigative effort. In many instances, these were one-armed studies that were so successful they became adopted. Examples are methotrexate for choriocarcinoma; vincristine and prednisone induction for acute lymphocytic leukemia; the MOPP regimen for Hodgkin’s disease; cytarabine and daunorubicin for acute myeloid leukemia; cisplatin, vinblastine, and bleomycin for testicular cancer; leukovorin and fluorouracil for colon cancer; and many others. After the initial reports of activity, these regimens were often compared with standard programs and demonstrated not only to be highly active, but more active than the prevailing predecessor regimens. Thus, there is a premium on good investigators conducting pioneering observational studies. Chemotherapy in single institutions may attain different results from the same regimen applied by many cooperating physicians in a broad-scale effort. Usually, this represents a different patient selection. If a regimen is superior in the hands of many different oncologic investigators, however, it is likely that its utility in the practice of medical oncology will be evident.

To ensure uniformity and reproducibility of procedures, research designs for studies of whatever size should be codified in a written protocol (Table 37.5). Long after a therapeutic program has been accepted into clinical practice the use of such protocols can be very useful in avoiding omissions, stipulating times for specific procedures, and ensuring that standard doses, thresholds, and end points are used. The possibilities for errors of dosage are sharply diminished when all personnel involved with patient care have access to a written protocol specifying the therapeutic regimen, particularly one that is immediately available on a computer. The oncologist is responsible for prescribing the proper drug and dose, but pharmacists and oncology nurses can serve as additional checks in the system. Personnel downstream from the oncologist could initiate an error for which the oncologist has to bear contingent responsibility. 6

Table 37.5. Topics to Be Covered in a Clinical Protocol.

Table 37.5

Topics to Be Covered in a Clinical Protocol.

Every oncologist’s office should be a research station. Every oncologist during his or her training was exposed to, and almost always was a participant in, clinical research. Virtually no regimen or treatment for any tumor is entirely satisfactory. There is much reason to anticipate that progress would be more rapid if clinical research were accepted as an integral part of the practice of medical oncology so that more oncologists and patients would participate than at present. The technology exists in medical informatics for community oncologists to ally themselves with their alma mater or other academic centers to participate in diagnostic, preventive, and therapeutic research trials using the computer, e-mail, and fax as expedient tools. Those oncologists who protest they have so heavy a work load that it prevents their devoting the necessary time to participate in clinical research, in fact, need a partner, or they will be depriving themselves and perhaps their patients of access to research advances.

As a part of the commitment to medical oncology, a medical oncologist should reserve a certain number of hours per week for participation in clinical research. This has the virtue of maintaining greater currency with ongoing investigation. Clinical investigation should serve as the bridge to fundamental science and the excitement in the new molecular biologic understanding of the cancer cell. By such association, the medical oncologist in practice may also forestall the burnout syndrome, which is discussed below.

It is not reasonable to expect that an individual in practice devote the same time and energy to clinical research as one who serves full time on the faculty of a university, research institute, or hospital. A set-aside for research, however, constitutes the same imperative commitment as a set-aside for education and updating. Initiation of one new patient on a protocol every second month should constitute a manageable burden of additional paper work for a practicing oncologist, and, using computer technology, even the paper work can be reduced or eliminated. A patient every other month per medical oncologist would accelerate clinical cancer research by data acquisition on nearly 60,000 more patients per year. Even a fraction of that newly generated information would seem like we had hit the mother lode. Furthermore, participation in such a study would ordinarily guarantee the patient that he or she gets a treatment equivalent to (or that is already) the best that is known. Patients with cancer are often apprehensive that they may not receive the best treatment. The medical oncologist can speak with greater authority when a deliberate comparison is being made, since the goal of such studies is toward improvement on the standard, not toward finding treatments that are equally good. Thus, it is not onerous to offer the current best or, possibly, something better.

Fundamental Science, Clinical Science, and Medical Art

The medical oncologist serves as the principal interface between cancer research in the laboratory and cancer research implementation in the patient. Many early chapters in this book deal with the structure and aberrant function of the cancer cell. Familiarity with this evolving understanding of cancer science is incumbent on every medical oncologist. A patient with cancer should be viewed in the context of the etiology, pathogenesis, pathology, and biochemistry of the particular neoplastic process.

The effects of the tumor and its products on the structure and function of the patient’s normal tissues, as well as the mind and emotions, define an understanding, in depth, of the disease process and of the patient in whom it takes place. It is not sufficient to order a therapy with the appropriate dose and schedule. A medical oncologist should understand the interaction, so far as it is known, of the administered drug with target molecules. Similarly, it is a given that there be a broad understanding of, and attention to, potential toxicities, which represent the drug’s effects on normal tissues. Therapies totally appropriate for someone whose disease might well be cured by judicious application of surgery, radiotherapy, and/or chemotherapy might be totally inappropriate if applied to someone with widely metastatic disease for whom no known cure exists. Therapy with curative intent, which may require “a walk through the valley of the shadow of death,” is ordinarily of relatively short duration and high intensity. On the one hand, conservatism aims at saving a life, not avoiding toxicity. On the other hand, treatment for palliative purposes would not ordinarily condone similar risks and iatrogenic effects that diminish the quality of life, even temporarily.

Another world of scientific enterprise that materially affects the possibility for curative cancer therapy deals with host support. The availability of powerful antibiotics and the implementation of platelet transfusions were intrinsic to early cures of the acute leukemias. The many new advances in colony-stimulating factors (filgrastim, sargramostim) have already significantly altered the prospect of drug-induced granulocytopenia. Recombinant erythropoietin can diminish drug-induced anemia. Continuing search for less cumbersome ways to deal with thrombocytopenia supports the use of single-donor pheresis. The era of cytokines and their manipulation is just beginning; combinations have not been explored in depth. The impact of cytokines on circulating hematopoietic progenitor (CD34) cells is a major one, making convenient the collection of such marrow-repopulating precursors to allow autologous stem cell transfusions as a supplement to, or even as a substitute for, autologous marrow transfusion. New antibiotics make granulocytopenia less ominous, and oral prophylaxis with antibiotics and antifungal agents have decreased hospital admissions. All these assets allow chemotherapy to be given more safely at the intended dose and schedule without delay or dose reduction.

The availability of far better antiemetic control makes cancer chemotherapy less dreaded. The emergence of psycho-oncology as a widely appreciated discipline has also made it possible for patients to strengthen their resolve to undertake approaches aimed at cure or to accept the unlikelihood of cure with greater serenity.

Chemotherapy Trials

A number of ethical issues are abrogated by the certainty that a specific patient’s disease is not potentially curable with today’s knowledge. For asymptomatic patients with indolent disease, precurability eliminates the need to rush to treatment. Many problems are initially best approached by masterful observation, particularly where age, comorbidity, and equanimity are factors. Where rapid course, portending symptoms, or inquietude prevail, however, therapy is indicated. For metastatic disease for which no cure is known, it is not only ethical but important that systematically designed investigation of new treatments be undertaken early in the course of the patient’s disease. This allows assessment of a drug’s activity before toxicity arises from conventional therapies that might limit dosing. Conventional therapies might also elicit resistance of one or another kind or immune system depression, which might foreclose the opportunity to recognize the activity of the candidate compound. A trial of candidate phase II agents prior to conventional chemotherapy for breast cancer has been conducted without significant compromise in response to the established regimen. 7 Most compounds should probably not be investigated in humans, however, before they have demonstrated greater activity against human cancer cells in vitro than against normal cells and, ordinarily, activity in vivo against transplanted or spontaneous tumors. The new categories of angiogenesis inhibitors affect the endothelium of the host, however, and are not included in this generalization. The predictive activity of human tumor xenografts in immunodeficient mice, in contrast to murine isografts or autochthonous murine tumors, has not been settled. 8

By the same token, for diseases with especially unfavorable outlook and rare therapeutic success, delays in introducing candidate compounds to ensure that they carry little or no risk of toxicity is an unwise investment of resources and time, let alone the patient’s short-lived opportunity for possible benefit. The outcome of unsuccessfully treated cancer is more ominous than the hazards of clinical investigation.

The design of chemotherapy trials is critical to the validity of the data produced. The essentials in the design of a protocol are provided in Table 37.5.

Intravenous medications which may be toxic to the venous wall, and vesicant if extravasated, commend the use of central venous access. When venous access is difficult because of anatomy or obesity, repeated needle sticks and much time are wasted in attempting peripheral venous access. Needle phobia is a perverse part of being under treatment; it can be largely obviated by establishing permanent venous access.

Adjuvant and Neoadjuvant Chemotherapy

Most cancer chemotherapy is given to patients with clinically manifest cancer. For a few disease entities, chemotherapy for obvious metastatic disease is curative. The advantage of treating patients whose body burden of residual cancer is smaller has proved so persuasive that the profession and patients have accepted the technique of postsurgical chemotherapy, acknowledging that this entails treating some patients whose body burden is already zero. Thus, adjuvant therapy after surgery has been demonstrated to be curative in several diseases for which surgery alone has low cure rates and chemotherapy alone cannot cure the manifest metastatic condition. Wilms’ tumor and osteosarcoma are the prime examples. In many diseases, there is evidence of prolonged disease-free survival and of longer survival, such as stage II and III breast cancer, 9, 10 stage III ovarian cancer, 11 and stage III colon cancer. 12 Since the adjuvant treatment is aimed at micrometastatic disease remote from the primary tumor, exploration of chemotherapy before surgery has been undertaken in a few types of cancer. In addition to earlier exposure of the micrometastases, when they may be smaller, this neoadjuvant, induction, or primary chemotherapeutic approach has two additional beneficial characteristics. First, regression of the primary lesion serves as a bioassay that the micrometastases will also likely be sensitive. 13 Failure of the primary neoplasm to regress affords an opportunity to shift chemotherapeutic treatment while there is still a chance of affecting the micrometastases with a new regimen. Second, regression of the primary tumor may make primary surgery unnecessary, allowing curative radiotherapy, as in some head and neck cancers and as shown in a large series of patients with breast cancer in France. 14 In other instances, surgery after chemotherapy may be technically easier, though not always less radical, since there is no certainty that every cell has been eradicated at the original boundaries. Induction chemotherapy has allowed a major reduction in amputations, however, in favor of limb-sparing surgery. Induction chemotherapy may also significantly enhance the effectiveness of radiotherapy.

Surrogate End Points

The medical oncologist must be deeply interested in methods to measure disease progress that anticipate the appearance of symptoms. Recognizing that new therapies will always be forthcoming, it is prudent to anticipate methods to test them that do not depend on such primitive assays as bidimensional measurements of tumor masses, or shadows on radiographs. These early methods have already been greatly improved by computed tomography, sonography, magnetic resonance imaging, endoscopy, and circulating tumor secretory products that represent marker molecules. Validation of each surrogate marker is requisite. Once established, as for human chorionic gonadotropin, a-fetoprotein, CEA, 5HIAA, calcitonin, PSA, CA 125, CA 15-3, CA 19-9, and some other similar molecules, the ability to monitor tumor activity is of major value. Recognizing disease progress by marker studies allows identification of inactive therapeutic regimens before clinical failure and provides opportunity for alternative action before the patient has major additional tumor burden and possibly before symptoms. Marker molecules are not infallible, however, and a tumor cell population may emerge during a cancer relapse from prior therapy that fails to secrete the marker that had been monitored.

Palliative Therapy

Palliative therapy no longer requires the patient to have symptoms that require palliation. The more logical construction is to prevent symptoms from appearing, or reappearing, using more discriminant guideposts than palpable or painful tumor. In the future, after the initial treatment, we can confidently anticipate that cancer management will depend upon indirect measures of tumor activity. Major therapeutic efforts will be aimed at tumors with a small body burden. Medical oncologists will be assessing biochemical, molecular biologic, or immunologic surrogates for tumor presence. Some of the reasons for considering some patients incurable are that therapeutic efforts have only been made when tumor body burdens exist that would prove too great for cure, even for sensitive tumors. The demonstrated efficacy of adjuvant chemotherapy for breast cancer implies that a low body burden of metastatic cancers, detectable only by markers, might be eradicable even with today’s therapies.

Laws of Therapeutics

Certain principles govern the application of therapies, no matter what the disease. These were enunciated more than a half century ago by Robert F. Loeb, Bard Professor of Medicine at Columbia University’s College of Physicians and Surgeons (Table 37.6). These simple rules have profundity and nearly universal applicability, and they pertain to neoplastic diseases. They must be tempered, however, by an understanding of the neoplastic process.

Table 37.6. Loeb’s Rules of Therapeutics.

Table 37.6

Loeb’s Rules of Therapeutics.

The first law is, if what you are doing is doing good, keep doing it. Vincristine plus prednisone is an excellent induction treatment for acute lymphocytic leukemia of childhood. In 1968, a question was raised: why not keep administering this highly active induction regimen rather than shifting to antimetabolite management? A cohort of children who were induced into remission by vincristine and prednisone were randomized to continue the induction treatment. They rapidly became resistant and relapsed, whereas the shift to antimetabolite treatment led to long-term sustained remissions and cures in children randomized to these arms. 15 Thus, the first law of therapeutics does not always apply to cancer where sequential treatment regimens may have special importance. Much of curative oncology relates to the biology of the unseen tumor, for which the current clinical status may not be informative. The first law seems more applicable to clinically recognizable disease.

The second law of therapeutics does have considerable universality, however: if what you are doing is not doing good, stop doing it. Most therapeutic regimens have little chance of success if after 8 weeks of treatment they have failed to elicit therapeutic benefit. Indeed, most patients show incipient tumor regression earlier. It is, nonetheless, advantageous to undertake a second month of treatment in most instances, since well-documented early increase in tumor diameter on radiographic examinations or increased pain can, indeed, be followed by tumor regression. If no symptomatic or objective benefit occurs after 2 months, it is usually legitimate to infer that a third month will not be beneficial. A few therapies are slower, however, and should be considered differently. New therapies that inhibit tumor growth by effects on stroma or that differentiate cancer cells may only cause tumor stasis, however, and require different assessments of effectiveness. Before stopping treatment, corroborating information should be sought by direct measurements, by radiography or by biochemical markers. Increased bony uptake of radionuclides can be a sign of bone healing, even of a previously unsuspected lesion, and is not a suitable end point. The appearance of a new metastatic deposit or the continued growth of previously documented tumor despite chemotherapeutic treatment speaks against continuing that regimen, since at least one clone of metastatic cells is resistant to it.

The second law of therapeutics does not extend to toxic effects, however, unless they are life threatening or profoundly disabling. With the chemotherapeutic agents available today, complete avoidance of toxicity would doom many patients to death from their neoplasm. Some patients can obtain cure and more can achieve meaningful remission by accepting the transient effect of intensive therapy that kills tumor cells and normal cells alike. The patient almost always recovers, but the less resilient tumor may not. Hippocrates’ admonition, Primum non nocere, is also subject to reassessment in oncology. 16 To treat a population of patients at a dose that would avoid toxic harm (i.e., lethal jeopardy) to any patient would surely exact a higher price in depriving others of adequate dose to achieve maximum benefit. Curative and subcurative cancer chemotherapy, as we know it today, is always toxic but rarely fatal. Attempts to abrogate toxicity for all by reducing the dose of an established regimen might compromise benefit for the majority. 17, 18 Dose adjustment for an individual may be necessary and prudent but must always be considered with respect to other means of mitigating toxicity without dose reduction.

The third law of therapeutics counsels against uninformed action: if you do not know what to do, do nothing. In many circumstances a rush to judgment, or worse a rush to “do something, anything” can be disastrous. Aside from oncologic emergencies, there is rarely an occasion when observing the evolution of symptoms and findings or seeking consultation with another individual for a fresh viewpoint is contraindicated because of time pressure. In the presence of pain, one should not delay pain relief, but other therapy may be delayed to gain necessary “thinking time.” In the presence of a differential diagnosis which includes diseases other than cancer, particularly infections, one must be certain that delay does not risk mortality or morbidity from the other possible disorders. The time invested for observation and consultation should not, thus, be extravagant.

It is an exceptional case, indeed, when a medical oncologist can consider treatment without a histologic diagnosis. Cytologic diagnoses may provide sufficient information in the presence of unambiguous clinical syndromes, but cytology of the bronchus, stomach, cervix, and body fluids has produced sufficient numbers of false-positive identifications to show that corroborating clinical syndromes are essential. Still, it is extremely useful to have histologic evidence, whenever possible.

The fourth law of therapeutics is: never make the treatment worse than the disease. This relates to total life equation: the price the oncologist knows the patient may be obliged to pay in present side effects to attain future real effects. Often the patient’s vision is foreshortened, since today’s symptoms caused by drug toxicity can be more severe than the original complaints related to the cancer. The medical oncologist must ascertain the patient’s attitude toward quality of life versus duration of life. It is a medical oncologist’s responsibility to counsel the patient concerning this weighty topic. It is critical to distinguish therapy with curative intent from a palliative orientation. The proper goal is maximal life at maximal quality. It is a modification of the commentary that one should die young as late as possible. For some patients, the toxic effects of treatment outweigh the value of possible extension of life. This perception is often related directly to age. The treatments imperative for patients in their forties may be inappropriate and unwise for patients in their eighties. Pain and disability from cancer may temper the desirability of certain therapies which offer only temporary and partial relief. It is not a kindness to defer death only transiently by rescuing a dying patient back to a raft of suffering. Heroic efforts are justified only when a meaningful therapeutic option exists.

It is inappropriate for the medical oncologist to substitute professional judgment for a patient’s ardent wishes when the patient strives to accomplish something that is a reasonable therapeutic goal. The medical oncologist must serve as a bastion of reality, however, advising the patient of what is possible and of what is likely. In the course of doing this, the laws of therapeutics and of humanity always include hope.

Truth Telling

Explanations of disease, anticipated therapies, protocols in which there is randomization, and unknowns must be tailored to the intellectual and emotional levels of the particular patient. It is never permissible to lie, but it may be prudent not to deposit all the truth, let alone all at once, on a patient who cannot accept the full details and ramifications of diagnosis and management. “Your patient has no more right to all the truth you know than to all the medicine in your saddlebags” was a humane and ethical tenet advanced by Oliver Wendell Holmes more than a century ago, and it still seems to be. 19 It is dishonest to twist facts or to deny specific features, such as the existence of metastases. By the same token, it is wrong to deny a patient an opportunity to make final dispositions with respect to self, family, religion, the law, and business by falsely stating that a disease is benign or cured. Families who assert that the patient must not know because he or she could not stand it are usually twice wrong: the patient often knows already or may be more distraught by being excluded from knowing; and the patient ordinarily incorporates the information into his or her life equation indistinguishably from other patients. A reading of Tolstoy’s masterful The Death of Ivan Ilyich should convince any doubting oncologist about the terror of uncertainty and the value of direct and honest, yet humane, interactions with the patient.

When a patient asks, “There is hope, isn’t there?” the oncologist can always be enthusiastically positive. Hope is a uniquely human characteristic, which sustains the will to continue, and all oncologists and all patients do hope for a better outcome.


Several states require that Do Not Resuscitate (DNR) orders be written on patient charts prior to death. In the absence of such orders, when a nurse finds a patient apparently dead she must, by law, initiate emergency calls for resuscitative efforts.

In circumstances where such laws exist, a medical oncologist should be meticulous in writing DNR orders and in explaining them to the family. When death comes from cancer as the expected final event of a gradual deterioration of vital forces, resuscitative efforts do not succeed. When we are unable to keep someone alive, the likelihood of bringing him or her back to meaningful life is infinitesimal. Resuscitative efforts should certainly be applied to patients with cancer who were not expected to die, since reversible phenomena, such as pulmonary emboli, cardiac arrhythmias, aspiration, and similar events, can provoke unexpected death in a patient with a neoplasm, just as in any other hospitalized or ambulatory patient. It is, however, in the circumstance of gradual decline and predictable disintegration of body functions that resuscitative efforts place great physical and emotional stress on the distraught family as well as on nursing and ancillary personnel, house staff, and attending physicians. Many patients, particularly the elderly and those apprised of the progress of their disease, can discuss the decision not to resuscitate with equanimity and, indeed, with a certain personal satisfaction of avoiding the fruitless anguish that such a procedure entails for the surviving family. Many patients are eager to sign living wills or to appoint a health-care proxy, if these possibilities are presented to them.

Because of the medicolegal implications involved, where particular religious scruples obtain or where families have emotionally uncontrolled members who cannot accept the anticipated death of a loved one, the medical oncologist should spend considerable time planning for an eventual death. Medical oncologists, through their organizations, should also invest effort to alter laws that place significant administrative burdens on them and their colleagues and that infringe on the appropriate professional practice of medicine. DNR forms are a technique of documentation and constitute further evidence that society has moved medicine onto a new plateau of accountability.

The medical oncologist should make known his or her intentions concerning the advisability of resuscitative efforts for each particular patient in advance, to forestall unnecessary trauma to patient, family, and staff, to forestall litigation, and to settle in advance any serious disagreements with patient or family. An impasse might occasion a medical oncologist to find a suitable substitute physician, if there is unresolvable conflict concerning the plans surrounding an anticipated death.

DNR orders do not imply that there be diminution of oncologic effort to control or palliate the disease before death. However, if good judgment indicates that continued efforts are fruitless and can only inflict suffering with no prospect of benefit, discontinuation of active therapy should always be accompanied by DNR orders.


A sense of frustration can affect anyone who encounters barriers to successful completion of an important task. This is particularly true of intellectual tasks and invisible barriers. When the barrier is a lethal disease about which the oncologist can do little that is effective, the frustration can be all consuming. Oncologists who encounter several instances of recrudescent or refractory disease in a short time (especially if punctuated by deaths of young or favorite patients, uninterrupted by counterbalancing compensatory successes) may well experience frustration, a sense of inadequacy, and depression. Frequent repetition of this cyclic phenomenon not uncommonly leads to the syndrome of burnout.

The medical oncologist knows that many of today’s cancers are precurable. To the extent that he or she can be involved, actually and conceptually, in the solution to these complex mysteries, the frustration is lessened. Cancer research, whether at the basic or clinical level, is held in high esteem by our fellow citizens. Group identity, “being one of the team,” helps to offset the self-deprecation when human tragedies mount despite one’s best efforts. The camaraderie of other oncologists helps because they battle the same enemy with the same primitive weapons. Another oncologist can understand the trauma and the distress; it is an encounter on familiar terrain.

The appreciation that the horizon is distant, and that oncologists are all working intently to see beyond it, puts present frustration in a more appropriate perspective. Involvement in the systematized academic pursuit, whether in an academic setting, a medical school outreach, an oncology society, or a local collaborative group, provides the security of collegial support, a buddy system, an anchor to windward.

A sound mind in a sound body implies rest, exercise, nutrition, and enjoyment. To ensure the last, the first three are prerequisites. Avocation and vacation are a portion of good mental health, included in the terms rest and exercise.

Donning the dress uniform of the grand enterprise against cancer, rather than the buckskin of the lone scout, can help imbue the oncologist with the identity and strength of the oncologic army. If these stratagems do not help the potentially burnt out oncologist find a new orientation and a more resilient response to the inevitable future traumas, he or she may well consider an alternative occupation. Many oncologists have moved honorably to laboratory, administrative, or pharmaceutical positions, where they are insulated from the vagaries of patients’ illnesses. It is better to have a happier oncologist isolated from patient contact than a depressed, and thus impaired, oncologist finally burnt out, still trying to perform at considerable personal discomfort, and perhaps at some patient jeopardy.

Nomenclature: Systeme Internationale (SI) Units

A system of quantitative nomenclature has been adopted in most parts of the world, except the United States. It is impossible to read an international medical journal without being thoroughly familiar with the SI units. They are presented in Table 37.7 so that readers can have ready access to a source for translation from the old nomenclature, characteristically American, which pervades this treatise.

Table 37.7. Representative SI (Systeme Internationale) Units for Laboratory Tests of Importance in Oncology.

Table 37.7

Representative SI (Systeme Internationale) Units for Laboratory Tests of Importance in Oncology.


The medical oncologist often serves as the final common pathway for the application of cancer research to patients. A complex corpus of information is available, which expands rapidly, both deeper into the nature of the cancer process and wider into new approaches that provide demonstrated effectiveness in therapy, prevention, or support.

The increasing appreciation that autocrine and paracrine factors are seemingly ubiquitous and influence the behavior of normal and neoplastic cells provides a variety of new targets for therapy. Many products of oncogenes exert their activity through autocrine or paracrine effects. Tumor suppressor genes and their products offer exceptional promise of elucidating how cellular biochemistry is regulated or is dysregulated in their absence, and thus may identify valuable targets for therapy. As a starter, the tumor suppressor gene products appear to be among nature’s ways of controlling a cell from manifesting cancerous behavior. The tide of fundamental discoveries is already washing away many of the unknowns and the flyspeck observations. It is axiomatic that certain cancers can be cured today without knowing the intimate nature of neoplasia. How better the day, perhaps soon upon us, when we know what we are doing!

Clinical accomplishments have similarly been exceptionally productive in the 44 years since the first cancer was cured with drugs. 4 A large assortment of drugs has since been provided. A wholly new array of genetically engineered drugs support host function, and others that are cytokines with anticancer activity are still early in their development. Imaging technologies have revolutionized the ability to detect, stage, and monitor cancers. Biochemical markers of tumor behavior are a principal fruit of immunologic study, but immunotherapeutics also hold promise.

There is probably no cancer in which some progress in diagnosis or therapy has not been achieved in the last decade. Similar achievement cannot be claimed for cancer prevention. Oncologists must assume greater responsibility for health preservation. Much could be accomplished by applying what is already known about lifestyle, diet, and exercise. Medical facts without political action were slow to change the tax on health that tobacco levies. A concerted effort within most states has begun, but a Federal role in managing the tobacco plague has been thwarted.

The horizon has never been closer. Although still distant, there are enough promising paths to follow that one of them may prove considerably faster than even reasonable optimism would suppose. The information that serves as our foundation, its rate of accrual, its revelations, and the demonstrated success of translating science to clinical applications augur well for the future of medical oncology and for cancer patients.


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© 2000, BC Decker Inc.
Bookshelf ID: NBK20782


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