Depression

[Guest guest]

Dear Terry,

Sorry to say, people on the " outside " of our issues do not understand.

Jimmy remarked today that when I am talking to our group on SKYPE, my voice

sounds different and I laugh and joke more. Apparently, he thinks I am more on

the serious side as of late. That's his observation, but I guess that is why I

spend more time at the computer, because I can reach out to our subscribers and

vice versa.

When someone reaches out and says, " I understand " , I know they really do.

An interesting article on depression and TKI's

Case Histories of Severe Depression With Imatinib and Dasatinib

Nick Mulcahy - January 16, 2009 - e-article

Seven patients receiving the tyrosine kinase inhibitors (TKIs) imatinib

(Gleevec, Novartis) or dasatinib (Sprycel, Bristol-Myers Squibb) have

experienced severe and treatment-related depression, according to clinicians

from the Dana-Farber Cancer Institute, whose letter on the subject was published

in the January 10 issue of the Journal of Clinical Oncology.

The correspondence calls for routine screening for suicide ideation and

depressive symptoms in all patients being treated with the small-molecule TKIs

imatinib and dasatinib. The Dana-Farber clinicians also call for dose-reduction

and, if necessary, treatment discontinuation as strategies to alleviate the

depression.

TKIs have a " tolerable adverse-effect profile " that includes fluid retention,

diarrhea, cramps, and fatigue, note the authors, one of whom, D. Block,

MD, is chair of the department of psychosocial oncology and palliative care at

the Dana-Farber Cancer Institute, in Boston, Massachusetts.

Dr. Block and her colleagues called TKI-associated depression " an

under-recognized small-molecule TKI effect. "

In an interview with Medscape Oncology, Dr. Block suggested that clinicians may

not have noticed depression in other TKI-treated patients. " We know that

diagnoses of depression are missed by nonpsychiatric physicians the majority of

the time, " she said.

A " striking pattern " exists in this series of 7 patients. " All were coping well

with their disease psychologically before imatinib/dasatinib therapy, yet

developed profound depression during treatment, with many experiencing complete

remission or improvement of symptoms after dose reduction or drug

discontinuation, " write the authors of the letter.

TKI-associated depression was only noticed among patients taking imatinib or

dasatinib. However, " it is not inconceivable that similar adverse effects may be

seen with other TKIs, " write the authors. TKIs share common mechanisms of action

and have overlapping molecular targets.

A spokesperson for Bristol-Myers Squibb, the makers of dasatinib, also noted

that the depression is not specific to 1 drug. " As the letter points out,

psychiatric disorders, including insomnia and depression, are not specific to

any one therapy and are manageable. [Chronic myeloid leukemia] is a

life-threatening disease and treatments such as [dasatinib] have led to

significant positive advances for patients, " said Henry of Bristol-Myers

Squibb in a communication to Medscape Oncology.

Novartis, the makers of imatinib, did not respond to Medscape Oncology about the

letter and case reports of depression.

Imatinib is indicated for chronic myeloid leukemia and gastrointestinal stromal

tumors (GIST), and dasatinib is also indicated for chronic myeloid leukemia, but

in patients with resistance or intolerance to previous therapy, including

imatinib. Both drugs are also indicated for use in patients Philadelphia

chromosome-positive acute lymphoblastic leukemia.

Imatinib and dasatinib are widely considered to have revolutionized the

treatment of both GIST and chronic myeloid leukemia.

Inconsistent Response to Depression Treatment

TKI-associated psychiatric symptoms responded inconsistently to standard

antidepressant treatment; according to the authors. " Most cancer-related

depressions are relatively responsive to low-dose antidepressant medications and

psychotherapy, and these TKI-related depressions are not, " said Dr. Block.

Only a small minority of patients with cancer develops depression related to

their illness, she added. The depressions seen in this series of patients was

not disease-related, according Dr. Block.

" The treatment-associated depression we saw with the TKIs occurred in temporal

relationship to starting and stopping the drug, in patients without a prior

history or family history of depression, was less responsive to treatment than

usual depressions, and was unusually severe, " she summarized.

In the event of TKI-associated depression, dose reduction may benefit some

patients. In severe treatment-refractory cases, discontinuation of the suspect

TKI should be considered, say authors of the letter.

The authors emphasized the importance of close and careful monitoring of

depression and suicide ideation. " Given the known elevated risk of suicide in

cancer patients, suicidal ideation should be treated as a psychiatric emergency,

with immediate referral to a psychiatrist for assessment, " they write.

Prescribing Information Lists Depression as Adverse Effect

The prescribing information for both imatinib and dasatinib lists depression as

an adverse event. However, depression is not highlighted with a warning or

precaution/caution for either drug.

In a clinical trial of imatinib among newly diagnosed chronic myeloid leukemia

patients, depression (all grades) occurred in 14.9% of patients, and grade 3/4

depression occurred in 0.5% of patients. In a trial of adjuvant imatinib among

GIST patients, depression (all grades) occurred in 6.8% of patients and grade

3/4 depression occurred in 0.9% of patients.

In the dasatinib prescribing information, depression is listed as occurring in

1% to more than 10% of patients; no mention is made of the depression grade.

Sample Story

The letter from the Dana-Farber clinicians details the 7 cases of depression

seen in their clinics, including the following abridged version of 1 of the case

reports.

A 55-year-old male with GIST, diagnosed in January 2000, underwent complete

resection, but the disease recurred in March 2001. He was " coping well " with his

metastatic cancer diagnosis, worked full time, and ran 4 miles daily.

Within 5 months of being prescribed 800 mg/day of imatinib, the patient

developed new severe depression. He experienced decreased libido, diminished

attention span, disorganization of thoughts, and intense feelings of

hopelessness, helplessness, and demotivation. He began to struggle in his

corporate leadership role. Symptoms proved refractory to standard therapy for

depression. The imatinib dose was reduced to 400 mg/day. The patient then

reported an increase in energy level with alleviation of depressed affect, which

was sustained for about 1 year.

Then, he again reported worsening depression, became periodically tearful, and

was unable to function at work. Eventually, imatinib treatment was discontinued

and he experienced prompt resolution of depression.

Over the course of this man's illness, he had been challenged 5 times with

high-dose imatinib (600 to 800 mg/day), write the letter authors. Each time,

imatinib therapy precipitated depression. In every instance but one, depressive

symptoms diminished or resolved completely with dose interruption.

Dr. Block has disclosed no relevant financial relationships. Those of her

coauthors are listed at the end of the published correspondence.

J Clin Oncol. 2009;27:312-313. Abstract

http://talkbloodcancer.com/index.php?option=com_fireboard & Itemid=2 & func=view & id=\

5290 & catid=7

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Cancer and the Immune System

In the peak of winter, those suffering from cancer of the immune system are also

fighting another battle - that against infections - as it is difficult for them

to stand the weather change and their chances of being infected increase 15-20

percent, doctors say. 'Due to weak immune system those suffering from some types

of cancers are more prone to infections that increases at the rate of 15-20

percent during winter,' Max Healthcare oncologist Amit Bhargava said. 'Cancer

treatments such as chemotherapy and radiation therapy weaken the immune system

which helps fight off infections; as a result, these cancer patients are at a

higher risk for getting or developing flu that can cause serious illness,' he

added. Cancer of the immune system also increases the chances of low immunity in

cancer patients.

Artemis Health Institutes head oncologist Ashok Vaid told IANS that people

suffering from cancer of the immune system like leukaemia (blood cancer) are

more prone to infections than people suffering from any other cancer. Apollo

Indraprastha Hospital's senior consultant surgical oncologist Feroz Pasha said

that the white blood cells (WBCs) that help the body to defend itself against

infections and foreign materials are fewer in the bodies of blood cancer

patients - resulting in a weak immune system. 'They should use immune-booster

supplements during their treatment and should keep a track of their WBCs as they

are more prone to get chest infections,' Pasha explained. In the peak of winter,

those suffering from cancer of the immune system are also fighting another

battle - that against infections - as it is difficult for them to stand the

weather change and their chances of being infected increase 15-20 percent,

doctors say.'Due to weak immune system those suffering from some types of

cancers are more prone to infections that increases at the rate of 15-20 percent

during winter,' Max Healthcare oncologist Amit Bhargava said.

'Cancer treatments such as chemotherapy and radiation therapy weaken the immune

system which helps fight off infections; as a result, these cancer patients are

at a higher risk for getting or developing flu that can cause serious illness,'

he added. Cancer of the immune system also increases the chances of low immunity

in cancer patients. Artemis Health Institutes head oncologist Ashok Vaid told

IANS that people suffering from cancer of the immune system like leukaemia

(blood cancer) are more prone to infections than people suffering from any other

cancer. Apollo Indraprastha Hospital's senior consultant surgical oncologist

Feroz Pasha said that the white blood cells (WBCs) that help the body to defend

itself against infections and foreign materials are fewer in the bodies of blood

cancer patients - resulting in a weak immune system. 'They should use

immune-booster supplements during their treatment and should keep a track of

their WBCs as they are more prone to get chest infections,' Pasha explained.

Other problems that this season brings for cancer patients are viral infections

and respiratory problems.'Once a virus attacks a cancer patient he should start

taking precautions or else chances of getting bacterial infection increase and

this could worsen the situation further,' Vaid said. Also one should always

check for symptoms of flu which can be high fever, severe headaches, muscle

aches and pains, extreme tiredness, cough and chest discomfort or sore throat,'

he added. People with cancer are also at higher risk of having bone

complications. 'Cancer and cancer treatments may also increase the risk of bone

complications. For this they should take vitamin D in plenty and sunshine is one

of the best sources of vitamin D,' Bhargava explained. He said that the patient

should spend at least 10 to 15 minutes in the sun at least twice a week. Also he

should eat more cheese and yogurt as they contain vitamin D. Cancer treatments

such as radiation therapy may result in skin problems as well. 'Keeping the skin

hydrated and healthy is important. Avoiding long baths or showers, using gentle

soaps, applying moisturizing lotions, drinking a lot of water can also help in

protecting the skin during winter,' Bhargava said. He, however, cautioned that

it is always advisable to consult a doctor before undertaking any of these

measures.

http://www.indiaenews.com/health/20090113/171021.htm