APOS Clinical E-Mail Update #19
5 August 2005

In this Update:

Which breast cancer patients would choose a group support program?

Cameron LD, Booth RJ, Schlatter M, Ziginskas D, Harman JE, Benson SRC.  Cognitive and affective determinants of decisions to attend a group psychosocial support program for women with breast cancer.  Psychosomatic Medicine 2005;67:584-589.

Younger women, more distressed, who believed that their immunity made a difference, and who were less apt to cope by avoidance were the ones who chose the psychosocial support program during breast cancer treatment.  The clinic offered all women a free, 12-week program that taught coping skills training and gave group support.  Groups of 8 to 11 women met with two facilitators weekly for two-hour sessions and received manuals and audiocassette tapes for home use.  The program covered relaxation, imagery, emotion regulation, setting priorities and goals, emotional disclosure through writing, anger management and meditation.  Women were approached 2-4 weeks after diagnosis.

Of the 110 women, mostly of European ethnicity and moderate economic circumstances at the University of Aukland, New Zealand, 56% did not choose the offer.  Based on prospective questionnaires and logistic regression analyses, the 44% of women who chose the group intervention had stronger beliefs that the cancer was mediated by altered immunity.  They had more cancer-related distress, lower tendency to avoidance, and younger age.  The researchers used a Common Sense Model to develop and test hypotheses about cognitive and affective predictors of illness behavior.  Personal control beliefs did not predict participation.

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Should psychosocial intervention for all patients in a gynecological cancer center in China be routine?

Chan YN, Lee PWH, Fong DYT, Fung ASM, Wu LYF, Choi AYY, Ng TY, Hextan YSN, Wong LC.  Effect of individual psychological intervention in Chinese women with gynecologic malignancy: a randomized controlled trial.  J Clin Oncol 2005;23:4913-4924.

This is a prospective, randomized controlled trial of individual psychotherapy in 155 newly diagnosed gynecological malignancies, treated from August 1999 to November 2000 at the University of Hong Kong and Queen Mary Hospital.  Patients reported on their quality of life every three months for 18 months in fixed-choice questionnaires.  Both the intervention group and the control group tended to get better over time in psychological symptoms, function, and quality of life.  In the intervention, both psychologists had more than 10 years clinical experience in counseling and treating cancer patients.  They met twice a week to discuss patients and to ensure comparable treatment approaches.  Treatment was every 2 weeks during active treatment and every 6 weeks thereafter to 18 months.

The principles of treatment were individually tailored with certain considerations: Exert caution not to ask patients to reveal or deal with their feelings about cancer prematurely at the start of the consultation.  Expand patientís perspectives on cancer treatment.  Work within values inherent in the Chinese culture.  Help patients see the integral link between thoughts, emotions, and physical well-being.  Promote an active and positive stance against cancer.  Respect individual differences in preferences, needs, choices.  Relaxation, psycho-education and supportive care, stress management, and management of specific symptoms like anxiety, depression and adjustment disorders with cognitive behavioral therapy.

Both the intervention group and the control group were similar with little prevalence of anxiety or depression.  They did not differ significantly at outcome.  The authors suggest that routine use of formal psychological therapies may not make the difference for psychological status or quality of life.

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If psychosocial intervention should not be routine, which cancer patients should get it?

Stanton AL.  How and for whom: Asking questions about the utility of psychosocial interventions for individuals diagnosed with cancer.  J Clin Oncol 2005; 23: 4818-4820.

In this accompanying editorial, Stanton comments on Chanís et al finding, no significant difference compared to standard care from an individual psychological intervention for Chinese women with gynecologic malignancy.  She suggests that future research must be crafted for those in most need.  Attributes of patients that moderate intervention effects should be evaluated in the analytical plan.  Distinct elements of an intervention may be critical.  Psycho-education, for instance, may be more helpful than supportive care.  Self-regulation and increased self-efficacy with regard to cancer-related issues produces larger effect sizes than intervention that do not have these components.

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Can a nurse-driven intervention for symptoms make a difference for men who have had treatment for localized prostate cancer?

Giesler RB, Given B, Given CW, Rawl S, Monahan P, Burns D, Azzouz F, Reuille KM, Weinrich S, Koch M, Champion V.  Improving the quality of life of patients with prostate carcinoma: a randomized trial testing the efficacy of a nurse-driven intervention.  Cancer 2005; 104:752-62.

This is a randomized trial showing the efficacy of a nurse-driven intervention to improve the quality of life of patients with localized prostate carcinoma.  This cancer care intervention was directed at sexual, urinary, and bowel dysfunction; cancer worry; dyadic adjustment; fatigue; and pain.  Sexual function and cancer worry were reduced compared to those patients who had received standard care; however, the benefits of the intervention were moderated in men who were highly depressed.

The men and their partners in the intervention group met once each month for six months, twice in person and then four times by telephone, with an oncology nurse who worked with an interactive computer program.  The program facilitated assessment and evidence-based strategies for each problem.  A high score in the assessment triggered the nurse to further assess the problem and to identify problem-solving strategies.  The first visit occurred 6 weeks after the cancer treatment was completed.  Patients were given a videotape to view at home on sexuality in the prostate cancer patient.  The film showed couples discussing how cancer had affected their sexuality and relationship.  At a second visit, one month later, the nurse used the computer program to evaluate problems and to discuss issues and concerns that had not been previously addressed.  The nurse then provided education and support tailored to the patientís needs.

Specific suggestions were Kegel exercises and scheduled voiding for urinary dysfunction.  Dyadic communication skills, information about Viagra, injections or other treatments for erectile dysfunction were common strategies for coping with sexual dysfunction.  Energy management, exercise, and priority setting were strategies for fatigue.  Active listening and advice about how to express feelings and perceptions to partners were skills for dyadic communication.

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Cytokines: Does IL-6 mediate social support and quality of life in ovarian cancer patients?

Costanzo ES, Lutgendorf SK, Sood AK, Anderson B, Sorosky J, Lubaroff DM.  Psychosocial factors and interleukin-6 among women with advanced ovarian cancer.  Cancer 2005;104:305-13.

Interleukin-6 (IL-6) may be an independent marker of health-related quality of life among ovarian cancer patients.  These researchers have previously found that women with gynecologic cancers who sought instrumental social support had lower levels of IL-6 at surgery and better clinical and functional status one-year after diagnosis.  In this study, they found that IL-6 and distressed mood were higher in patients.  Social attachment was associated with lower levels of IL-6 in peripheral blood after age and disease stage were considered.  The same pattern was found in ascites fluid.  They postulate that social support may play a protective role with respect to IL-6 elevation.  This was a study of 61 ovarian cancer patients at the University of Iowa.

It is notable that IL-6 stimulates proliferation, attachment, and migration of ovarian tumor cells and may play a role in metastatic processes of ovarian cancer.  It has also been a marker for disability, stress, and depression.

Social support was measured by the 24-item Social Provisions Scale that assessed how well participants perceived current relationships.  With this instrument, patients reported how their relationships fostered the possibility of information and advice, the availability of aid when needed, the recognition of the patientís abilities, a sense of belonging to a group, closeness and intimacy, and feeling needed by others.

Anxious mood or depressive symptoms were not related to peripheral IL-6 levels.  Women with a history of depression did not have higher IL-6 levels.  More fatigue and worse physical function was related to IL-6.  IL-6 in peripheral blood in this study was also strongly related to IL-6 in the area of the tumor.

IL-6 is secreted during hypothalamic-pituitary axis activation and is closely involved in feedback loops with stress hormones.  Stress hormones like norepinephrine and epinephrine stimulate production of vascular endothelial growth factor (VEGF) by ovarian tumor cells, and these effects are blocked by propranolol.  VEGF is the cytokine important for angiogenesis.  By this mechanism, one could postulate an interaction between distress, prognosis, tumor growth, and cytokine level.  On the other hand, IL-6 may be seen as one of the pro-inflammatory cytokines that fight infection and simultaneously cause fatigue, less social interaction and depressed mood.  This study offers data suggesting that IL-6 is an interesting mediator between social support, reduced stress, depression and ovarian cancer growth.

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When cytokines are elevated, how is thinking affected?

Meyers CA, Albitar M, Estey E.  Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome.  Cancer 2005;104: 788-793.

Patients with acute myelogenous leukemia or myelodysplasia have elevated cytokines and cognitive dysfunction before treatment.  At MD Anderson Cancer Center in Houston, Texas, 54 patients with AML/MDS were studied just before treatment.  65% had fatigue.  Levels of cytokines: IL-1, IL-1(receptor-antagonist), IL-7, IL-8, and tumor necrosis factor-alpha, were highly elevated compared to normals.  IL-6 was associated with worse executive function.  Ratings of fatigue were related to levels of IL-6, IL-8, and TNF-alpha.  IL-8 actually correlated with better memory function.  More than 40 percent of patients had impairments in learning new information, and one third had poor fine motor coordination.  One-quarter had difficulties with executive function.  These deficits followed a frontal-subcortical pattern and did not immediately change in the first month of treatment.

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Does a testosterone patch increase libido for post-menopausal women?

Braunstein GD, Sundwall DA, Katz M, Shifren JL, BusterJE, Simon JA, Bachman G, Aguirre OA, Lucas JD, Rodenberg C, Buch A, Watts NB.  Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women.  Arch Intern Med 2005;165:1582-1589.

Oophorectomy is associated with reduction in sexual desire in 30-50% of women.  This change in libido has been ascribed to loss of androgens from the ovaries.  Replacement estrogen may increase the globulins that bind sex hormones exaggerating that testosterone deficit.

Transdermal testosterone at 300 microg/d for three months in women with oophorectomy who also receive estrogen have improved sexual function and well-being.  This 24-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial of 447 women (aged 24-70, average 50 years old) evaluated three doses of testosterone: 150, 300, and 450 micrograms/day.  There was no evidence of a treatment effect at the lowest dose and no additional benefit at the higher dose; however, 300 mcg was significantly better than placebo.  In this study, there were no women with breast cancer.  The patch was well tolerated.  Skin reactions at the site of the patch were the most common adverse event (27%).  There was a large placebo response in this study.

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Can serotonin reuptake inhibitors be safe antidepressants in patients with carcinoid syndrome?

Dolenc TJ, Williams MD.  Selective serotonin reuptake inhibitors and patients with carcinoid tumor.  Psychosomatics 46:370-372.

Patients with carcinoid tumor have flushing, diarrhea, and abdominal cramping.  Abnormal mental status has been reported.  The syndrome results from an interaction between kinins, prostaglandins, and 5-HIAA metabolites produced by a neuroendocrine tumor.  A carcinoid tumor may produce excessive serotonin.  In one reported patient, sertraline (Zoloft), a serotonin-reuptake inhibitor, led to diarrhea and the recognition of a carcinoid tumor.  The confusion, agitation, orthostatic hypotension, diarrhea, flushing, tachycardia, and diaphoresis imitated a serotonin syndrome.

When patients with carcinoid syndrome develop major depressive disorder, serotonin agonists are therefore added with caution.  The literature is very limited on this uncommon disease.  Psychiatrists at the Mayo Clinic report here 5 patients with carcinoid tumors who were treated for depression with serotonin reuptake inhibitors without difficulty.  Four of 5 had improvement in their mood.  In one patient, the only side effect was sedation from fluoxitene.  Only one of these had a high urinary 5-hydroxyindoleacetic acid (5-HIAA) value suggesting higher serotonin production.

Carcinoid syndrome is seen in 5-7 percent midgut carcinoid tumors, usually when there are metastases.  Midgut tumors come from small intestine, appendix, or proximal colon.  An ovarian carcinoid can cause carcinoid syndrome without metastases.  Foregut tumors, in the lung, stomach or pancreas can also cause flushing.  Not all carcinoid tumors produce serotonin, and infusion of serotonin does not reproduce flushing.

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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