56: Cancer

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CHAPTER 56 Cancer


The seriousness of the diagnosis of cancer challenges the capacity to survive, to set a course in life, and to fulfill hopes and dreams. Over the twentieth century, even as cancer treatments improved and some patients were cured, psychiatrists in the tradition of humane psychiatry used their skills to stand by patients who were overwhelmed, to help them to speak in their own voices, to make complex treatment choices, and to shape the rest of their life or the end of life. Psychiatrists have offered expert diagnosis and management of co-morbid psychiatric syndromes and collaborated with oncologists so that treatable psychiatric illness does not stand in the way of technical oncological care. Specific cancer-related or cancer-treatment–related neuropsychiatric syndromes (Table 56-1)15 can be recognized and treated. Psychiatrists can help patients to cope with physical symptoms, developmental losses, changes in relationships, and the effects of cancer on families.

Table 56-1 Neuropsychiatric Side Effects of Cancer Drugs

Tamoxifen, toremifene: hot flashes, insomnia, mood disturbance; at high doses tamoxifen can cause confusion
Anastrazole (Arimidex), letrozole (Femara), exemestane (Aromacin): hot flashes, fatigue, mood swings, and irritability; cognitive effects are not known
Raloxifene (Evista): no cognitive side effects noted
Leuprolide (Lupron), goserelin (Zoladex): hot flashes, fatigue, and mood disturbance
Androgen Blockade
Leuprolide (Lupron), goserelin (Zoladex): hot flashes, fatigue, and mood disturbance
Flutamide (Eulexin), bicalutamide (Casodex), nilutamide (Nilandron): as above
Dose-related, variable psychiatric side effects including insomnia, hyperactivity, hyperphagia, depression, hypomania, irritability, and psychosis
Treated by ad hoc antipsychotics easily with cancer patients
Other drugs with benefit: lithium, valproate, lamotrigine, and mifepristone
Dexamethasone (Decadron) 9 mg equals 60 mg of prednisone; psychiatric side effects are associated with this dose level
Steroids used as part of an antiemetic treatment with chemotherapy infusion, with lymphoma protocols as high as prednisone 100 mg for 5 days, with nervous system radiation treatment to reduce swelling, with taxanes to reduce side effects
Depression, cognitive impairment, hypomania, psychosis, fatigue, and malaise
Responsive to antidepressants, hypnotics, antipsychotics, stimulants, and antianxiety agents
Associated with autoimmune thyroiditis that may increase or decrease thyroxine; check thyroid function
May inhibit metabolism of some antidepressants by P450 enzymes CYP1A2, CYP2C19, CYP2D6
Interferon-beta has less neurotoxicity
Delirium, flu-like syndrome, dose-dependent neurotoxicity, and hypothyroidism
Vincristine (Oncovin), vinblastine (Velban), vinorelbine (Navelbine)
Neurotoxicity is dose-related and usually reversible. Fatigue and malaise are noted. Seizure and SIADH are uncommon. Postural hypotension may be an aspect of autonomic neuropathy.
Less toxicity is noted with vinblastine and vinorelbine.
Procarbazine (Matulane)
Mild reversible delirium, depression, and encephalopathy
A weak MAO inhibitor
Antidepressant use must consider the timing of procarbazine or risk serious interactions
Disulfiram-like effect; avoid alcohol
Asparaginase (Elspar)
Depression, lethargy, and delirium with treatment
Cytarabine (ARA-cell, Alexin)
High-dose IV treatment (over 18 g/m2/course) can cause confusion, obtundation, seizures and coma, cerebellar dysfunction, and leukoencephalopathy. Older patients with multiple treatments are more susceptible. Delirium and somnolence can be seen 2-5 days into treatment. Those with renal impairment are more vulnerable.
Fludarabine (Fludara)
Rare somnolence, delirium, and rare progressive leukoencephalopathy
5-Fluorouracil (5-FU)
The primary neurotoxicity is cerebellar, but encephalopathy with headache, confusion, disorientation, lethargy, and seizures has also been seen.
Rare deficiency of enzyme that metabolizes dihydropyrimidine dehydrogenase (DPD) is associated with greater exposure and more toxicity.
Fatigue is the most common side effect.
Cerebellar syndrome and rarely seizure or confusion or parkinsonism may be noted.
High-dose IV thymidine may be an antidote for toxicity.
Capecitabine (Xeloda)
Related to 5-FU, but with less neurotoxicity
Causes neurotoxicity particularly when the route is intrathecal or high-dose IV (usually over 1 g/m2). The toxicity, which is usually reversible, is related to peak level and duration of exposure. Leptomeningeal disease or other conditions that break the blood-brain barrier may impair drug clearance. Prolonged exposure allows the drug to pass through the ependyma of the ventricles to cause leukoencephalopathy. The risk is greater in patients also exposed to cranial radiation. Intrathecal methotrexate may also cause seizures, motor dysfunction, chemical arachnoiditis, and coma. Serum levels are followed closely; folinic acid (leucovorin) rescue is an antidote. Alkalinization may lower the serum level.
There is a dose- and route-related risk of delirium.
Pemetrexed (Alimta)
An antifolate given with supplements of folate, intramuscular vitamin B12, and dexamethasone. It is associated with a 10% rate of depression and fatigue.
Gemcitabine (Gemsar)
Fatigue, flu-like syndrome, and a rare autonomic neuropathy
Etoposide (Eposin)
Postural hypotension and rare disorientation
Carmustine (BCNU)
Delirium, only at high dose, rare leukoencephalopathy
Rare leukoencephalopathy
Ifosfamide (Ifex)
Transient delirium, lethargy, seizures, drunkenness, parkinsonism, and cerebellar signs that improve within days of treatment
Risk factors: liver and kidney impairment
Thiamine or methylene blue may be antidotes
Rare reversible posterior leukoencephalopathy, parietal, occipital, frontal with cortical blindness.
Peripheral neuropathy, poor proprioception, and rarely autonomic
Hypomagnesemia secondary to renal wasting
Vitamin E (300 mg), amifostine may limit peripheral toxicity
Hearing is decreased due to dose-related sensorineural hearing loss
Neurotoxicity only at high doses
Oxaliplatin (Eloxatin)
Acute dysesthesias of hands, feet, perioral region, jaw tightness, and pharyngo-laryngodysesthesias
Paclitaxel (Taxol)
Sensory peripheral neuropathy not worse with continued treatment
Rarely seizures and transient encephalopathy, and motor neuropathy
Given with steroids
Docetaxel (Taxotere)
Like paclitaxel but less neurotoxicity
The newest class of medications, specific inhibitors of kinase signaling enzymes, do not typically cause major behavioral side effects.
However, their toxicity related to overlapping effects on several kinase pathways has not been fully defined. Hypertension has been an important side effect related to inhibition of the vascular endothelial growth factor (VEGF). Asthenia or feelings of weakness are commonly reported.
Imatinib (Gleevec)
Can cause fluid retention and fatigue, rarely low phosphate; confusion and papilledema
Sunitinib (Sutent)
Hypothyroidism, TSH should be checked every 3 months
Sorafenib (Nexavar)
Fatigue and asthenia and rarely hypophosphatemia
Bevacizumab (Avastin)
A monoclonal antibody that blocks VEGF-binding, causes fatigue, and rarely causes reversible posterior leukoencephalopathy
Drowsiness and somnolence improve over 2-3 weeks, dose-related, associated with dizziness, orthostatic hypotension, tremor, loss of libido, hypothyroidism, and rarely confusion
Bortezomib (Velcade)
Postural hypotension and asthenia; confusion, psychosis, and suicidal thoughts have been reported
Rituximab (Rituxan)
Headache and dizziness
Trastuzumab (Herceptin)
Headache, insomnia, and dizziness

IV, Intravenous; MAO, monoamine oxidase; SIADH, syndrome of inappropriate antidiuretic hormone; TSH, thyroid-stimulating hormone.

Since Weisman and co-workers explored how to help patients cope with cancer when they are demoralized,68 psychiatrists have tried to understand who the patient was before the diagnosis and the nature of the existential predicament. The psychiatric interview can assess the personal past, present plight, anticipated future, regrets, salient concerns, physical symptoms, disabilities, coping strategies, and psychiatric vulnerability (Table 56-2).7

Table 56-2 Concerns of Patients with Specific Cancer Types

Cancer Type Likely Concerns
Prostate cancer Significance of serum prostate-specific antigen (PSA) test results: anxiety
  Once diagnosed, the initial choices are watchful waiting, surgery, or radiation treatment
  Side effects of surgery or radiation: incontinence or erectile dysfunction
  Sexual function and dysfunction
  Androgen blockade and its effects on fatigue and loss of sexual interest
Breast cancer Body image related to mastectomy or to reconstruction
  Adjuvant chemotherapy and its side effects: alopecia, weight gain, fatigue, and impaired concentration
  Menopausal symptoms: insomnia, sexual dysfunction, and hot flashes related to adjuvant treatment, antiestrogens, or aromatase inhibitors
  The question of prophylactic mastectomy
  Sexuality and fertility (or infertility)
Colon cancer Adjustment to surgery or an ostomy
  Body image and sexual function
  Bowel dysfunction
Lung cancer Physical limitations of reduced lung capacity
  Postthoracotomy neuralgia
  Guilt about nicotine addiction (past and present)
Ovarian cancer Anxiety about the tumor marker CA125
  Sexual dysfunction and infertility
  Pain and recurrent bowel obstruction
Pancreatic cancer Maintenance of adequate nutrition
  Poor appetite
  Bowel function (and the need for pancreatic enzymes and laxatives)
  Depressed mood
Head and neck cancer Facial deformity
  Dry mouth
  Poor nutrition
  A weak voice and difficulty with communication
  Posttreatment hypothyroidism
  Alcohol and nicotine dependency
Lymphoma Corticosteroid-induced mood changes
  The need for recurrent chemotherapy and its effects
Hodgkin’s disease Posttreatment hypothyroidism
Osteosarcoma Amputation/prosthesis vs. bone graft
  Impaired mobility
  Postthoracotomy neuralgia

Denial and “Middle Knowledge”

Patients often seem to know and want to know about the gravity of their illness, yet they often talk as if they do not know and do not want to be reminded about their cancer.9 Weisman used the expression “middle knowledge” for the space between open acknowledgement of death and its utter repudiation. Patients may deny facets, implications, or mortal threat of an illness.9 Middle knowledge is most apparent at transition points (such as a recurrence of cancer). However, denial is an unstable state, almost impossible to maintain against even the reluctant patient’s inner perceptions. To preserve a relationship, patients often deny their knowledge of impending death to different people at different times.10 Tactful discussion of mortality allows patients to be responsive to those most close as long as possible.9

Hope and the Doctor-Patient Relationship

Physicians convey respect by exploring the patient’s capacity to cope. That respect allows the patient to nurture courage and resiliency.11 Trust between the patient and the physician is borne out of mutual respect. Patients regain a sense of control as they appraise and reappraise what choices to make. Presenting the facts about an illness does not break trust between a patient and a doctor. Furthermore, hope is not merely related to prognosis. The patient’s capacity to hope is also related to an ego ideal and to the conviction of one’s influence on the world. As the physician sustains the patient’s self-esteem, a sense of purpose adds value to life regardless of the time frame. The psychiatrist’s capacity to listen to a patient in a nonjudgmental way allows patients to express doubts and weaknesses, to accept who they are and why they see things as they do. The physician’s presence there protects patients from abandonment and offers a place where they can explore what is meaningful.11,12

Medical Choices

The psychiatrist also clarifies with the patient the medical understanding of what choices are feasible. Unfazed by personal shock, anxiety, and denial, and armed with a medical education, the psychiatrist is in an excellent position to understand (better than the patient) the individualized medical plan. Diagnosis, treatment, and prognostic decisions are complex as set forth by medical experts. As the psychiatrist learns how the patient thinks, and if necessary, adds appropriate psychopharmacological treatment for symptoms or Axis I diagnoses, the psychiatrist can maintain a focus on necessary anticancer treatments that are most likely to give the best outcome. Focusing on problems, setting priorities, making clear what the patient is doing and not doing about a problem, and exploring strategies are key elements of care. This technique allows patients to make the decisions that are most critical to them. Meanwhile, the psychiatrist, in collaboration with oncology staff, sorts through differential diagnoses as new psychological symptoms develop and the medical condition and treatment progress. The psychiatric assessment includes evaluation of physical symptoms, psy chiatric diagnosis, and the differential diagnosis. The work includes education about how to support significant others and how to allow help or to relinquish control to those who have shown themselves trustworthy. The goal of honest communication is to support acceptance, to reduce bitterness, and to replace denial with the courage to confront what cannot be changed.10


In the study of newly diagnosed cancer patients, Weisman and associates found that the peak of distress varied from 1 or 2 days to 3 months, but that the intense distress lessened over time.13 Those more depressed and anxious, who had less financial and social support, more alcohol abuse, more troubled relationships, and more burden from illness, were more distressed. The researchers learned that high-risk patients were unable to generate a number of alternate coping strategies.7 Vulnerable patients tended to overuse strategies that were ineffective for finding relief and resolution. Weisman and associates defined a treatment to reduce distress, to correct deficits in coping, to reclaim personal control, and to improve morale and self-esteem. Patients were asked to examine their plight in relation to cancer (their current concerns); to articulate their understanding of what might interfere with good coping; and by looking beyond, to use options that were feasible for finding satisfactory solutions. Staff took the view that change was possible and that patients could be helped to take steps on their own behalf, as problems were broken down into manageable proportions. They focused on coping and adaptation rather than on psychopathology; they conveyed an expectation of positive change, a sense that options and alternatives are seldom completely exhausted, and an awareness that flexibility in perceiving problems helps to attain additional information and support. They compared a brief psychodynamic and behavioral technique; both were effective in reducing distress and denial.7


Weisman and Worden defined a screening instrument and a concise interview to identify patients at high risk for psychosocial vulnerability and ineffective coping (because those individuals were most apt to benefit from psychosocial intervention). To make screening more efficient, Zabora and co-workers validated the Brief Symptom Inventory–1814 to the Index of Current Concerns (now a Brief Symptom Inventory–11)15 to identify the more anxious and depressed patients with more somatic symptoms and distress. To call attention of oncology staff to distressed cancer patients, Holland and colleagues in the National Comprehensive Cancer Network (NCCN) guidelines operationalized a visual nomogram (a distress thermometer score ≥ 5) with a variety of needs assessed.16

Psychosocial Interventions

Weisman’s work foreshadowed major studies of preventive psychosocial interventions for cancer patients. Fawzy and colleagues1720 described a 6-week structured group intervention for patients with melanoma Stage I and II; it included health education, stress management, coping skills, and supportive group psychotherapy. They also taught simple relaxation exercises (e.g., progressive muscle relaxation, guided imagery or self-hypnosis, as well as problem-solving and coping methods). The interaction of the patients within the group provided a source of emotional support.1720 The group with 6 weeks of treatment had a survival benefit at 5 to 6 years, but this comparative benefit was not as evident in the tenth year.

Spiegel and others developed a group therapy supportive-expressive intervention for women with metastatic breast cancer. In two randomized multisite studies, the benefit for survival has not been found, but the ability of this intervention to reduce distress, to offer patients social support and safe conduct, and to increase their ability to confront difficult challenges has been documented.2124

Chochinov25 focused on conserving dignity at the end of life by asking patients what they feel is most important and what they want their loved ones to remember. Informed by the work of Frankl,26 Greenstein and Breitbart27 and Breitbart and colleagues28 reported on a group intervention for advanced cancer patients who focus on faith and meaning.

Combinations of interventions augment patients’ coping skills.29 Teaching about relaxation has had a benefit for cancer patients,29,30 and a variety of educational interventions, tailored to disease type and phase (e.g., stress management, cognitive therapy, and behavioral training), have improved coping and decreased distress.31 As parents with cancer worry about their children, Rauch and Muriel32 have offered guidance.