APOS Clinical E-Mail Update #17
18 May 2005

In this Update:

Does collaborative care for depression work in a public Hispanic cancer setting?

Dwight-Johnson M, Ell K, Lee P-J, Can collaborative care address the needs of low-income Latinas with co-morbid depression and cancer? Results from a randomized pilot study.  Psychosomatics 2004;46:224-232.

This report argues against the idea that depression is an inevitable and untreatable consequence of cancer and poverty.  This is a pilot study of collaborative depression treatment in a low-income public sector, Los Angeles County/ University of Southern California oncology program.  The patients were Latinas with cervical or breast cancer who entered the program from community-based clinics, local screening programs, and the medical center.  The oncologists had a one-hour educational session on the diagnosis and treatment of depression in cancer patients and were given pocket reference guides.  Woman at least 3 months from diagnosis were identified by bilingual study recruiters and were screened with the Personal Health Questionnaire (PHQ-9).  The PHQ-9 asks the criteria essential to the diagnostic statistical manual diagnosis of major depressive disorder. If depressive symptoms were recognized at outset and one month later, the patients were included.  Patients who were suicidal, terminal, or who had a history of bipolar disorder or psychotic disorder were excluded.

Depressed patients were randomly assigned to the multifaceted oncology depression program or to usual care.  The intervention included an education session with a master’s-level social worker trained to provide manualized problem-solving psychotherapy.  That counselor supported adherence to antidepressant medication and assisted with systems navigation.  Patients could choose problem-solving treatment or medication as their first line treatment.

Of the 269 patients (two-thirds of those eligible) who agreed to be screened for depression, 68 (25%) met criteria for major depressive disorder or dysthymia.  Additional cases of depression were recognized one-month later.  Patients in the collaborative program were more likely to have any and greater than 50% improvement in symptoms than those in usual care.  Twelve patients received four or more sessions of problem-solving therapy.  Three chose medication as first-line treatment, and four had medication added after an inadequate trial of problem solving treatment.  Barriers to treatment were feeling too medically ill, forgetting appointments, child care responsibilities, transportation problems, personal or family problems, financial problems, moving away, and stigma.

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How bad is care for Latina women with cancer and depression in a public cancer program?

Ell K, Sanchez K, Vourlekis B, Lee P-J et al.  Depression, correlates of depression, and receipt of depression care among low-income women with breast or gynecologic cancer.  J Clin Oncol 2005;23:3052-3060.

This study describes how unlikely it is for women with cancer and depression to get treatment for depression in the low-income, public sector, Hispanic setting.  It is no surprise that state-of-the-art care for depression leads to better outcomes, and the study above confirms better outcomes in this setting.

An ongoing, randomized trial of a structured case management intervention to improve adherence to cancer treatment among 500 women with breast or gynecologic cancer provided an opportunity to look at the prevalence of depression and depression treatment at the same medical center noted above, the Los Angeles County/ University Southern California oncology low income public sector oncology program.  The majority (79%) of women were Hispanic.  Using the PHQ, the nine item questions about symptoms of major depressive disorder, the researchers found 30% breast cancer patients and 17% gynecologic cancer patients had moderate to severe levels of depressive disorder.  Only 12 % of those who met criteria for depression were receiving medications for depression and only 5% sere seeing a counselor or meeting with a cancer support group.

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Has the prognosis and role of chemotherapy for metastatic colorectal cancer changed?

Meyerhardt JA, Mayer RJ.  Drug therapy: systemic therapy for colorectal cancer.  New Engl J Med 2005;352:476-487.

This is an excellent review of the treatment of colorectal cancer.  It shows that the nature of the illness has changed since 1994 and summarizes how.  Systemic chemotherapy has led to an improvement in the quality of life and survival of patients with metastatic disease.  One year survival has moved from 34 to 50 percent.  Median life expectancy without chemotherapy is in the range of 6 months; the median survival with the newer regimens have increased to 14-16 months.

The toxicity of fluouracil, the backbone of treatment, includes stomatitis and neutropenia when it is given every four to five weeks on five consecutive days.  When the boluses are weekly, diarrhea is more common.  Continuous infusion and capecitabine (Xeloda) leads to more hand-foot syndrome.  Patients with stage III disease benefit from intravenous flurouracil or fluoruracil plus leucovorin as adjuvant agents.  The likelihood of five-year overall survival has moved from 51 percent to 64 percent.

Irinotecan (Camptosar or CPT-11) causes diarrhea, bone marrow suppression, nausea, omitting, and alopecia, but adds further benefit for patients treated with fluororuacil.

Oxaliplatin and fluorouracil are highly synergistic.  A cumulative dose-dependent sensory neuropathy, numbness or tingling of the hands, feet and the oral or perioral regions, sensitive to cold temperatures, is the signature side effect.  Oxaliplatin is combined with bolus fluorouracil and leucovorin in a treatment regimen known as FOLFOX that has shown greater benefit than the fluorouracil regimen alone.

The authors go on to discuss cetuximab (Erbitux) and the angiogenesis inhibitor bevacizumab (Avastin).  Bevacizumab is used in combination with intravenous fluoruracil containing regimens as initial therapy for patients with advance colorectal cancer.

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Why does cervical cancer still occur?

Leyden WA, Manos M, Geiger AM, Weinmann S, Mouchawar J, et al.  Cervical cancer in women with comprehensive health care access: attributable factors in the screening process.  J Natl Cancer Inst 2005;97:675-83.

Pap tests are still important.  The test must include the endocervical component.  These authors investigated why cervical cancer still occurs in women who have access to health care.  They reviewed the cases of cervical cancer that occurred from 1995 to 2000 in long-term members of 7 prepaid comprehensive health plans and examined their records for three years before the diagnosis.  The majority with cervical cancer (56%) had not had any Pap tests in the 3 months before diagnosis.  One third of cases were due to failure of the Pap test to detect the cancer, and 13% had no follow-up.  Older age, poorer neighborhood, and low education were associated with failure to screen.  Older and poorer women were more likely to have had inefficient follow-up.  Women over 65 contributed 17% of cases even though women are not advised to get regular Pap tests after 65.  Testing for human papillomavirus may identify the women who should be tested at older ages.  This study looked at those patients who had comprehensive health care and had been in the group for at least 3 years.  We assume that lack of services would add to the risk of inadequate screening and to the risk of cervical cancer.

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Which patients with non-small cell lung cancer get brain metastases and how soon?

Gaspar LE, Chansky K, Albain KS, Vallieres E et al.  Time from treatment to subsequent diagnosis of brain metastases in Stage III non-small-cell lung cancer: A retrospective review by the Southwest Oncology Group.  J Clin Oncol 2005;23:2955-2961.

Brain metastases are so common in non-small cell lung cancer and so critical to quality of life, and the interval from entering treatment to development of brain metastases is short.  In this retrospective review of 422 patients, 64% had disease progression, and 20% (n=54) of these were in the brain only.  Another 6.5% were in the brain and other sites simultaneously.  All but 23% relapsed in the brain within 12 months.  Non-squamous histology and young patient age (less than 50 years old) were the predictors of greater risk of early relapse with brain metastases.  The cumulative risk of failure in the brain for patients with adenocarcinoma was 22%.

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What happens to prostate cancer survivors 4 to 8 years later?

Miller DC, Sanda MG, Dunn RL, Montie JE, Pimentel H et al.  Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.  J Clin Oncol 2005;23:2772-2780.

Each of the treatments for primary prostate cancer, radical prostatectomy, external radiation, and brachytherapy can achieve better than 95 percent cancer-specific survival at 5 years.  This report details patients' statements of symptoms from 4 to 8 years after treatment.  They prospectively used the Expanded Prostate Cancer Index Composite questionnaire to assess 964 patients a median of 6 years from treatment.  The overall response rate was 74% (n=709).

Urine control can improve in the first two years after radical prostatectomy but not substantially thereafter.  For men treated with brachytherapy or external radiation, urinary incontinence is a greater concern after 2 years in this study.  At least one other study did not have this finding.

Brachytherapy patients had less urinary irritative symptoms over time; improvement occurs within one to two years from the time of implantation.  Urinary irritative and obstructive symptoms may occur in the first two years after brachytherapy but may continue to improve up to eight years after treatment.  Diarrhea, painful bowel movements, and rectal bleeding all occur more after radiation treatment.  These can persist after the first two years but are less prominent over time.

Over the four to eight years from treatment, sexual function declined in the external radiation treatment group only.  This change was paralleled by changes in the control sample, suggesting that aging was an important variable.  In this group of men who had prostate cancer treatment, 38% of those with radical prostatectomy, 17% of those with external radiation treatment, and 19% of those with brachytherapy were current users of medications or devices to aid erectile function.

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Who is more prone to intrusive cancer-related thoughts among breast cancer survivors?

Matsuoka Y, Inagaki M, Sugawara Y, Imoto S, Akechi T, Uchitomi U.  Biomedical and psychosocial determinants of intrusive recollections in breast cancer survivors.  Psychosomatics 2005;46:203-211.

While formal diagnosis of post-traumatic stress disorder is uncommon among breast cancer survivors, the intrusive thoughts about the cancer experience have been associated with persistent depression or anxiety.  Younger, poorer, more isolated women with worse medical problems and women with neuroticism, negative life events, pre-cancer trauma, trait anxiety, and psychiatric diagnosis are more likely to suffer post-traumatic symptoms.  This consecutive series of Japanese breast cancer patients three to 15 months after surgery included 63 women with intrusive recollections and 92 without.  Neuroticism by the Eysenck measure, pre-cancer intrusive recollections, and the number of cancer patients in relatives by marriage were determinants of intrusive recollections.  Radiotherapy was also associated with intrusive thoughts.  Chemotherapy and tamoxifen use were associated with lymph node involvement, so only lymph node involvement was entered into the analysis.  Eysenck defined neuroticism as "an anxious, worrying individual, moody and frequently depressed… finding it difficult to get back to an even keel after each emotionally arousing experience." This paper suggests that these patients are more prone to intrusive recollections, other factors contribute as well.

Thorsen L, Skovlund E, Stromme SB, Hornslien K, Dahl AA, Fossa SD.  Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy.  J Clin Oncol 2005;2378-2388.

A supervised home-based flexible training program in young and middle-aged cancer patients shortly after curative chemotherapy led to better cardiorespiratory fitness but did not affect the patients' experience of fatigue, mental distress or health-related quality of life.  These 111 adult patients under 50 in Oslo, Norway, were in treatment for lymphoma, breast, gynecologic, or testicular cancer.  The exercise period was 14 weeks with a minimum of two exercise sessions per week lasting at least 30 minutes.  Walking was the exercise most apt to be chosen, but more strenuous activities were also chosen.  The control group had no personalized training, but they were told to be as physically active as they would have been without hearing about the study.  Cardiorespiratory fitness was measured on a bicycle ergonometer; mental distress was measured by the Hospital Anxiety and Depression Scale.

The magnitude of change attributed to exercise programs for cancer patients completing chemotherapy in mental distress, fatigue, and health-related quality of life is not consistent in the literature.  The outcome of this study shows that the intervention was enough to change fitness, but fitness alone may not override problems in mood and severity of fatigue.  The authors discuss methodological issues that may have contributed to this finding, but they have shown a program that does improve fitness over usual care.  Better fitness is a good outcome, even if the subjective symptoms have not changed.  We know that causes of mood and fatigue are more complex than cardiorespiratory fitness alone.

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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