APOS Clinical E-Mail Update #11
30 August 2004

In this Update:

Before starting systemic treatment, do breast cancer patients have cognitive deficits?

Wefel JS, Lenzi R, theriault R, Buzdar AU, Cruickshank S, Meyers CA.  ĎChemobrainí in breast carcinoma? A prologue.  Cancer 2004;101:466-475.

This study highlights the presence of cognitive deficits in women with breast cancer prior to chemotherapy or hormone antagonist treatment.  Since previous studies of the cognitive effects of adjuvant chemotherapy have not been prospective and since other methodological criticizes have been raised, the cognitive complications of systemic treatment are still controversial.

These researchers at University of Texas M.D. Anderson Cancer Center examine the cognitive functions of 84 women with non-metastatic breast carcinoma who were beginning hormone treatment or chemotherapy in three separate prospective trials.  No subject had a current neurologic or psychiatric disorder; nor were subjects using narcotics, antiemetics or steroids in the week before testing.  Neuropsychologic testing included attention, memory, language, excecutive function, visuospatial and motor function, depression and anxiety.  The tests include the Beck Depression Inventory, the MMPI depression and psychasthenia scale, the State-Trait Anxiety InventoryóState score.  Testing for language included the MAE Controlled Oral Word Association and sequential commands and the Boston Naming Test.  Executive function testing included the Trail Making Test part B, Category Test, and WAIS-III similarities.

Of 84 patients, the researchers knew about a history of hormone replacement treatment in 67.  Of these 30 (45%) had used HRT, and the median time to the last use was 52 days.

Symptoms of mild to moderate anxiety and /or depression were reported by 26% of patients, and these were more likely to be cognitively impaired.  Befrore the start of treatment 35% exhibited cognitive impairment, mostly in verbal learning (18%) and memory function (25%).

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Would venlafaxine help peripheral neuropathy pain?

Rowbotham MC, Goli V, Kunz NR, Lei D.  Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.  Pain 2004;110:697-706.

Neuropathic pain is a common occurrence in cancer patients.  In this sample of 244 patients with stable diabetic neuropathy, 6 weeks of venlafaxine extended-release, 150-225 mg for pain was superior to placebo when studied in a double-blind, plaebo-controlled study.  The dose of 75 mg was not as effective.  This study evaluated the effect on neuropathic pain over 6 weeks.

Venlafaxine has been used in doses of 75 to 150 to suppress hot flashes in women with breast cancer who are taking anti-estrogen treatments.

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Does pain disturb sleep no matter what stage of sleep?

Lavigne G, Brousseau M, Kato T, Mayer P, Manzini C, guitard F, Monplaisir J. Experimental pain perception remains equally active over all sleep stages.  Pain 2004;110:646-655.

It is interesting to note that noxious stimuli awaken healthy patients in all stages of sleep.  In this study of 13 healthy adults, the noxious stimulus of intramuscular 5% hypertonic infusion was compared to vibro-tactile and control stimulations of isotonic infusion and auditory stimulation.  To evaluate sleep arousal, polygraphic signals and heart rate were recorded.  Both noxious and vibratory and audiotory stimulations caused the same rate of arousal in sleep Stage 2, lighter sleep; but the response frequency to noxious stimuli was similar in sleep stages 3 and 4 and in REM.

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What predicts delirium in cancer patients?

Ljubisavljevic V, Skelly B.  Risk factors for development of delirium among oncology patients.  General Hospital Psychiatry 2003;25:345-352.

In order to assess risk factors for delirium, Lujisavljevic and Kelly at Princess Alexandra Hospital in Wooloongabba, Queensland, Australia followed 113 oncology patients through 145 admission over 10 weeks.  There were 26 cases of delirium (18% of admissions) with 4 patients dying.  Those who lived all had reversible delirium.  The risk factors were advanced age, cognitive impairment, low albumin, bone metastases, and hematological malignancy.  Hospitalization was mean 8.8 days for those who became delirious vs. 4.5 days for those who did not.

The Confusion Assessment Method questionnaire was completed daily by the evening nurse.  It typically takes 5 minutes.  Nurses were trained in weekly sessions; 80% were compliant.  The principal investigator reviewed these reports, confirmed the diagnosis of delirium by DSM criteria, and alerted the treating medical team.  The early recognition and prompt treatment of delirious patients that evolved from this study highlights the cost of delirium in a well-treated population of cancer patients.  Think what the cost would have been if the assessment and treatment were not timely.

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Could acetylcholinesterase inhibitors treat opioid-induced delirium?

Slatkin N, Rhiner M.  Treatment of opioid-induced delirium with acetylcholinesterase inhibitors: a case report.  J Pain Symp Manage 2004;27:268-273.

This is a case report of a 55-year old woman who developed myoclonus and delirum when the dose of opioid was increased.  First physostigmine and then oral donepezil led to improvement in cognition.  This raises the possibility that the cholinergic system is important in opioid-induced delirium that may respond to treatment with cholimimetic agents.  The patient had ovarian cancer, partial small bowel obstruction and medications: fentanyl patch, morphine, alprazolam, gabapentin, fluoxetine, and trazodone.  The narcotic dose changed from the equivalent of 300 mg/day morphine to 500 mg/day.  This change was related to an increase in fentanyl patch to 175 micrograms per hour and morphine for break-through pain.  The improvement with donepezil seemed to be dose dependent.

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How likely are brain metastases in common tumors?

Barnholtz-Sloan JS.  Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE.  Incidence proportions of brain metastases in patients diagnosed (1973-2001) in the metropolitan Detroit cancer surveillance system.  J Clin Oncol 22;2004;2865-2872.

When evaluating the mental status of a patient with cancer, it is helpful to understand the likelihood of brain metastases.  The incidence rate of metastatic brain tumors is 8.3-11 per 100,000.  As cancer patients live longer, the possibility of metastatic brain tumors increase.  Most patients with metastatic brain metastases have lung cancer, but melanoma goes to the central nervous system more often than other cancers.  This study looked at patients diagnosed with primary lung, melanoma, breast, renal or colorectal cancer between 1973 and 2001 in the Metropolitan Detroit Cancer Surveillance system.

The total incidence proportion of brain metastases was about 10% for all these sites combined, about 20% for lung, 7% for melanoma and renal cancer, and 5% for breast.  Colorectal cancers contributed 1.8%.  The rates were higher for African American patients in all sites and higher for women with lung cancer and men with melanoma.  Brain metastases were more likely in women with breast cancer who had been diagnosed in the younger 20-39 year old range.

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Should you recommend exercise during prostate radiation treatment?

Windsor PM, Nicol KF, Potter.  A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.  Cancer 2004;101:550-557.

Home-based , moderate-intensity walking led to a significant improvement in physical functioning and no worse fatigue for men who were receiving localized radiotherapy for prostate cancer in this prospective randomized, controlled trial of aerobic exercise.  The sample of 66 men were split between exercise and control conditions.  Fatigue measured by the Brief Fatigue Inventory and by the distance walked in a modified shuttle test before and after radiotherapy were the outcome variables.  Patients kept a patient-activity diary and were contacted weekly during radiation treatment.  The treatment group had the benefit of a physiotherapist who encouraged adherence to the exercise program.  Men in the control group, who took things easy if they were tired, had an increase in fatigue at the end of treatment, while the treatment group did not.  The treatment group walked significantly farther at the end of treatment.

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When does the remedy for delirium add to the problem?

Morita T, Tei Y, Shishido H, Inoue S.  Olanzapine-induced delirium in a terminally ill cancer patient.  (letter) J Pain Sympt Manage 2004;28:102-103.

Morita et al, who have been studying delirium in cancer patients reported a case of delirium made worse by olanzapine.  The exacerbation was attributed to its anticholinergic side effects.  A 57 year old man with lung cancer and paralysis from verterbral metastases was treated with fentanyl 1200 micrograms/day.  Brain MRI showed a solitary small metastasis to the cortex.  Nausea was the most troublesome symptom, and olanzapine was used after bethanmethazone, chlorpheniramine, metoclopramide, prochlorperazine, and famotidine had failed.  Nausea improved on 2.5 mg and then 5 mg on day 5.  Delirium began on day 7 and disappeared when olanzapine was withdrawn.

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What characteristics of the physician are associated with the new hospice patientís wish to hasten death?

Kelly BJ, Burnett PC, Pelusi D, Badger SJ, Varghese FT, Robertson MM.  Association between clinical factors and a patientís wish to hasten death: Terminally ill cancer patients and their doctors.  Psychosomatics 2004;45:311-318.

Clinician predictors of a high score on the wish to hasten death in a terminally ill patient included the clinicianís perception of the patientís lower optimism and greater emotional suffering, the patient indicating a wish to hasten death, the doctor willing to assist (if requested and legal), and the doctor reporting less training in psychotherapy.  This study creatively contributes to the understanding of the physician as he manages a patient who wishes to hasten death.  As the authors point out, the doctorsí task includes exploration for the patientís suffering, finding the role for psychological intervention, provision of a continuing relationship, and facilitating family needs.  This sample of doctors was selected because one of their patients had been referred to the palliative care setting and had identified the physician as important in the individualís care.  Each doctor completed a self-report questionnaire.  The interviewer did not know whether the patient was high or low scoring on the wish to hasten death.  The 256 patients were matched with their doctors for the analysis.  The modelís power increased when these physician factors were combined with patient factors previously identified.  Patient factors included a higher perceived burden on others, higher depressive symptom scores, and lower family cohesion.  These factors combined with the physician factors and the setting of the patientís recent admission to hospice.  The doctor-patient relationship and the importance of the physicianís ability to understand his own perception of suffering in another human being are important elements in the care of the patient at the end of life.

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What do we know about interventions on cancer screening?

Supplement: Promoting Cancer Screening: Lesson Learned and Future Directions for Research and Practice.  Cancer Vol 101 Issue S5 (1 Sept 2004).

This supplement represents the state of research and practice on screening for cancer.  The scope of intervention research and studies to improve adherence to cancer screening tests are reviewed.  The authors discuss methodology for conducting behavior modification interventions.  The issues are approached at the level of public policy, organizational system, practice setting, provider, and patient.  Informed decision making is applied to cancer screening.

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What side effects do patients expect with cancer treatment?

Hofman M, Morrow GR, Roscoe JA, Hickok JT, Mustian KM, Moore DF, Wade JL, Fitch TR.  Cancer patientsí expectations of experiencing treatment-related side effects.  Cancer 2004;101:851-857.

Often side effects develop when patients expect them.  These researchers surveyed patients in multiple community clinical oncology practice sites to see what they expected for side effects of cancer treatment.  They were most likely to expect fatigue, nausea, sleep disturbance, weight loss, hair loss, and skin problems.  The median number of expected symptoms was nine.  Younger patients, more educated patients, and women expected more side effects.

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Donna B. Greenberg, MD, Associate Professor of Psychiatry at Harvard Medical School and Psychiatric Consultant in the Massachusetts General Hospital Cancer Center, Dana Farber Partners Cancer Care