BBM 3-10-2008 J. Menten1 Belgian Breast MeetingProf Dr J Menten Radiation-Oncology Brussels 3-10-2008 Coordinator palliative Care Breast Cancer: comfort.

BBM 3-10-2008 J. Menten 1

Belgian Breast Meeting Prof Dr J MentenRadiation-Oncology

Brussels 3-10-2008 Coordinator palliative Care

Breast Cancer: comfort therapy

BBM 3-10-2008 J. MentenBBM 3-10-2008 J. Menten 22

Breast cancer:Breast cancer:

1 Pain treatment1 Pain treatment2 Co-analgesics2 Co-analgesics3 Adjuvant medication3 Adjuvant medication4 Advance care planning4 Advance care planning


Symptoms leading to diagnosisSymptoms leading to diagnosis

Base: all who has specified cancer (n=4947)S3. What symptoms lead you to see the doctor prior to your diagnosis of cancer?

n=4947

31%

27%

11%9%

7%

5%5%4%

3%2%2%2%2%2%

1%1%1%1%1%1%1%1%1%1%1%

5%

Pain is the key symptom

leading to cancer diagnosis

followed by a lump and chronic fatigue

31%


HCP with main responsibility for management of cancer pain

Base: (n=573)

Oncologist 42%

General practitioner 19%


palliative therapy

palliative care

Onc

olog

ical

pat

ient

s100 %

0

curative therapy

Diagnosis Death

30%

60%

PAIN PREVALENCE

80 to 90%

Pain Treatment


% of patients reporting pain in cancer % of patients reporting pain in cancer

56%56%

20%

88%

Strong opioids in elderly palliative patiëntsStrong opioids in elderly palliative patiënts Menten & al. J Current med opinion, 2002Menten & al. J Current med opinion, 2002

Each point concerns ≥ 20 patiënten

116 65

Lung Prostate Breast Gastro-Intestinal

Mean dose TTS-fentanyl in function of tumortype

+200 mg p.o.morfine equivalence/d

+600 mg p.o.morfine equivalence/d

Total Pain (C. Saunders)

Physical

Spiritual

Psychological

Social

Suffering

PAIN

Interdisciplinary approach!!!


05

10152025303540

not 5-299 300-599 >600

morphine mg/day

Median survival in home care in function of daily morphine dose

P = 0,002 Mantel-Cox

P=0,029 Breslow-analysis

Bercovitch et al. Cancer 2004; 101 (6):1473-7

1 Pain: Opioids & life expectancy?1 Pain: Opioids & life expectancy?

Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, BelgiumEducational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, Belgium

The art of cancer pain treatment

Is not fishing at random

in the ocean of available pharmaceuticals,

but choosing as an expert

the right drug, the right dose and combination of drugs

at every moment for every individual cancer patient

Educational Symposium: “Comprehensive cancer pain management “ ECCO-13Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, J. Menten, Leuven, BelgiumBelgium

2 Co-analgesics: -are not analgesics,

but have some intrinsic analgesic effect

-in combination better pain relief

analgesic sparing effect

-mostly they do not provide complete analgesia

-just a decrease in pain

-inform patients about this compliance


2 Co-analgesics:

All Oncologists: 1-NSAID’s

2-Corticosteroids

3-Antidepressants

4-Anticonvulsants

5-Bisphosphonates

Expert advice: -topical therapies

-NMDA-receptor antagonists

-α-2 Adrenergic or GABA-agonists

-Neuroleptics (neuropathic pain)

-Benzodiazepines (paroxysmal neuropathic pain)

Neuropathic pain


Co-analgesics 2 Corticosteroids

-Headache (brain metastases) R/ -Dexamethasone 4-24 mg./d (po, iv, sc)

-Methylprednisolone 16-128 mg/d (po, iv, im)

-Liver capsule distention ( metastases)

-Extensive tissue destruction or invasion (especially nerve)

-Sometimes - GI–sub-/obstruction, pruritus, excessive sweating- Dyspnoea (continuous low dose)- Nausea and vomiting refractory to standard treatment


Co-analgesics 2 Corticosteroids

-high doses (>6 mg dexamethasone, >32mg methylprednisolone):

R/ divide dose over day and last dose before 4 pm. (insomnia!!)

-side effects after long-term use of moderate or high doses: -moon face, buffalo hump, fluid retention -candida infections-gastro-intestinal side effects

-avoid combination with NSAID’s-give gastric protection

There is no substitute for them!!


Co-analgesics 3 Antidepressants

-Amytryptiline (Redomex®) is the standaard -extensive body of clinical evidence-few clinical trials

central analgesic effect in neurogenic pain

-New selective serotonine re-uptake inhibitors -fewer side-effects-have a mixed analgesic effect-are not reimbursed


Co-analgesics 3 Antidepressants

General guideline : -Continuous pain: antidepressants-Paroxysmal pain: anticonvulsants

-Antidepressants practical guidelines: - start in low dose: 10 – 25 mg at night- add the starting dose every few days (up tot 50-150 mg)- no pain relief within a week: stop & replace the drug by another- stop if somnolence and/or dry mouth - never stop them abruptly after use >10 d, but taper gradually


Co analgesics

5 Bisphosphonates are indicated for : -≥1 bone metastase(s)-±relatively stable chronic bone pain-in patients with a life expectancy of at least some months

not for quick pain relief at the end of life-pain relief: clodronate < pamidronate < zoledronate < ibandronate

Multiple Event Analysis (adapted from Rosen et al., Cancer 2003)

Hazard ratio (Zole 4 mg versus Pam)

In favor of Zole In favor of Pam

P value

.030Total

Breastcancer

Multiple myeloma .593

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 20

.025

*Hypercalcemia of malignancy is included as an SRE.

Hazardratio

0.841

0.932

0.799

Zoledronic acid 4 mg significantly decreases the risk of developing a skeletal complication (16% reduction)

Intravenous Ibandronate significantly reduces Intravenous Ibandronate significantly reduces skeletal morbidityskeletal morbidity

Mea

n S

MP

R

All new

bone ev

ents

Verte

bral

fract

ures

Non-ver

tebra

l

fract

ures

Need fo

r

radio

ther

apy

Need fo

r

surg

ery

Placebo

Bondronat 6mg

2.0

1.5

1.0

0.5

0

p=0.004

p=0.023 p=0.396

p=0.011

p=0.075

SMPR: 1.48 vs 1.19, p=0.004

Trial not powered for individualcomposite endpoints

Body JJ, et al. Ann Oncol 2003

SMPR= skel.morbidity period (12w) rate

11-04-2311-04-23 BBM 3-10-2008 J. MentenBBM 3-10-2008 J. Menten

Effects on pain (VAS)Effects on pain (VAS) (mean ± SEM)(mean ± SEM)

Days

Mancini I, Body JJ; JCO 2004

7

6

5

4

3

2

1

00 7 21 42

*

*

*

VAS

(from Hillner et al., ASCO 2003 update, JCO 2003)

Bisphosphonates for metastatic breast cancerBisphosphonates for metastatic breast cancer

- WHEN TO START? -- WHEN TO START? -

evidence of bone destruction on imaging

only abnormal bone scan : « not recommended »

Probably “never” (≠ antineoplastic treatment !!)

“… continued until evidence of substantial decline in a

patient’s general performance status” (ASCO guidelines)

But we lack adequate prospective cost-effectiveness

studies & risk of excessive treatment

? WHEN TO STOP ???? WHEN TO STOP ???


Systemic treatment of bone metastasesSystemic treatment of bone metastases

General principles:General principles:

--Look to response rates, to survival, ... to Look to response rates, to survival, ... to “Quality of Life”“Quality of Life”

--“listen to the patient”,“listen to the patient”,has thehas the patient benefit from the therapy ? patient benefit from the therapy ?

Clinical improvement, no radiological response Clinical improvement, no radiological response continue continue

If there is clear radiological response but:If there is clear radiological response but:

- no “symptom” benefit for the patient - no “symptom” benefit for the patient stop ?stop ?

- intractable treatment related adverse effects - intractable treatment related adverse effects

that give more burden than the diseasethat give more burden than the disease stop treatmentstop treatment


Systemic treatment of bone Systemic treatment of bone metastasesmetastases

General principles:General principles:

-For bone metastases -For bone metastases there is frequently pain control there is frequently pain control

in the absence of measurable tumor regression.in the absence of measurable tumor regression.

--No pain control, but other clear benefit of the treatment: No pain control, but other clear benefit of the treatment:

““treat the pain”treat the pain”: radiotherapy, analgesics,: radiotherapy, analgesics,

NSAID’s, biphosphonates, …ask advice…NSAID’s, biphosphonates, …ask advice…interdisciplinarity !interdisciplinarity !

-Oncological treatment -Oncological treatment

Palliative treatment Palliative treatment palliative care palliative care Teamwork


Co-analgesics Bisphosphonates in bone pain

-Complications: “osteonecrosis of the jaw” = class phenomenon

-rare (1-2%) but serious functional deficit -difficult pain problem-resistant to treatment = irreversal!

-Risk factors are treatment of bisphosphonates combined with-dental extractions or surgical interventions of the jaws-chemotherapy-corticosteroids

Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, BelgiumBelgium

3 Adjuvant medication:- have no intrinsic or indirect analgesic effect

- counteract the side effects of analgesics

-constipation

-nausea & vomiting

-sedation


Adjuvant drugs Laxatives

All patients taking strong opioids regularly will develop constipation !!

-Prophylactic laxatives: always!

R/osmotic laxatives contact laxatives

clysma

Adjuvant drugs Anti-emetics

-Make them available ….but start them when You start strong opioids and taper the dose when possible

Somnolence

-after opiodsdisappears spontaneously after 24 – 48 h-Exceptionally: Methylfenidate (Rilatine®) 5 + 5 mg


The role of adjuvant medication The role of adjuvant medication in metastatic breast cancerin metastatic breast cancer

We have for metastatic breast cancer patients : We have for metastatic breast cancer patients : – 5-0H-T3 receptor antagonist (anti-emetics)5-0H-T3 receptor antagonist (anti-emetics)– hematopoietic growth factors hematopoietic growth factors – recombinant erythropoietinrecombinant erythropoietin– low molecular weight heparinlow molecular weight heparin– biphosphonatesbiphosphonates

Each of them :Each of them :

– is very expensiveis very expensive– does not improve survivaldoes not improve survival– is given to improve quality of lifeis given to improve quality of life

Cost effectiveness?Cost effectiveness?


Not every adjuvant drug that:

-can be given

-is reimbursed

has to be given!!

Individualize treatment while

listening to/assessing the needs of each patient

Medicinal cannabis and cancer Medicinal cannabis and cancer palliationpalliation

Cannabis SativaCannabis Sativa plant plant


Abbreviations: THC, Abbreviations: THC, ΔΔ9-tetrahydrocannabinol; CBD, cannabidiol, FDA, United States Food and Drug Administration; MS, multiple sclerosis; NOC/c,9-tetrahydrocannabinol; CBD, cannabidiol, FDA, United States Food and Drug Administration; MS, multiple sclerosis; NOC/c,Notice of Compliance with Conditions Policy for its indicated use.a Who have failed to respond adequately to conventional antiemetics.Notice of Compliance with Conditions Policy for its indicated use.a Who have failed to respond adequately to conventional antiemetics.

Engels K; de Jong A. et al. Medicinal cannabis in oncology. European journal of cancer 43 (2007) 2638-2644.Engels K; de Jong A. et al. Medicinal cannabis in oncology. European journal of cancer 43 (2007) 2638-2644.

Cannabinoid Registered name

Route ofadministration

Indications Firm Legal status

Dronabinol(syntheticTHC)

Marinol® Oral

Anorexia / weight loss (aids)

Nausea and vomiting (Cancer)a

SolvayPharmaceuticals(Marietta, GA,US)

FDA approval April 2003

Nabilone(dronabinolanalogue)

Cesamet® OralNausea and vomiting (Cancer)a

ValeantPharmaceuticals(Aliso Viejo, CA,US)

FDA approval May 2006

THC & CBD(isolated fromCannabisSativa L.)

Sativex® SublingualSymptomatic relief of neuropathic pain (MS)

GWPharmaceuticals(Salisbury, UK)

Approval NOC/cpolicy inCanadab

Limitedavailabilityin Spain and UK


Legal Dutch medicinal cannabisLegal Dutch medicinal cannabis

Since Sept 2003 available for clinical research, Since Sept 2003 available for clinical research, drug formulation development and on prescription drug formulation development and on prescription for patientsfor patients

3 medicinal Cannabis Flos varieties: Bedrocan3 medicinal Cannabis Flos varieties: Bedrocan®®, , BedrobinolBedrobinol®® and Bediol and Bediol®® to make thee of or to inhal to make thee of or to inhal

41.25 Euro – 43.50 Euro per 5g ~10 doses 41.25 Euro – 43.50 Euro per 5g ~10 doses

(expensive – not reïmbursed)(expensive – not reïmbursed)


Medical use in oncologyMedical use in oncology

(delayed or anticipatory) chemo- or radiotherapy (delayed or anticipatory) chemo- or radiotherapy induced nausea and vomitinginduced nausea and vomiting

Nabilone may have a role in patients whose nausea and emesis is not Nabilone may have a role in patients whose nausea and emesis is not adequately controlled by 5-HT3 receptor agonists and Emendadequately controlled by 5-HT3 receptor agonists and Emend®® and may and may also help in patients with anticipatory nausea.also help in patients with anticipatory nausea.

Ware M. et al. A review of nabilone in the treatment of chemotherapy induced nausea and vomiting. Ther Clin Risk Ware M. et al. A review of nabilone in the treatment of chemotherapy induced nausea and vomiting. Ther Clin Risk Manag. 2008 February; 4(1):99-107Manag. 2008 February; 4(1):99-107

Cancer-associated anorexiaCancer-associated anorexiaInsomnia reliefInsomnia reliefMood elevationMood elevationAppetite stimulationAppetite stimulationAnalgesia : Analgesia : equal analgesic effect to codeine or 20 mg morphine/d. equal analgesic effect to codeine or 20 mg morphine/d.


Side effectsSide effects

Narrow therapeutic windowNarrow therapeutic windowAcute psychoactive effects: dizziness, Acute psychoactive effects: dizziness, dysphoria, depression, hallucinations and dysphoria, depression, hallucinations and paranoiaparanoiaImpaired psychomotor functionImpaired psychomotor functionPotential synergistic effects with other Potential synergistic effects with other psychotropic agents and alcoholpsychotropic agents and alcoholRisk of developing dependenceRisk of developing dependence


4 Advance directive planning

How long do we continue with anticancer treatment

As long as treatment is effective

Untill all available drugs have been used

As long as the patient asks for therapy

As long as the PS ≥70%


4 Advance directive planning

-Inform the patient progressively

-Define realistic goals

-Discuss what has to be done if treatment fails

-Supportive therapy palliative care


% patients with symptom control in relation to obj tumour respons

Impact of respons on QoL: breastca

Geels et al, J Clin Oncol 2000

PD

SD

CR/PR


6-StervensprocesConclusion

-Optimise pain treatment from diagnosis on

-Use co-analgsics and adjuvant medication

-Individualize treatment ~ needs of the patient

-Inform patient clearly

-about realistic benefits

-about realistic endpoints

BBM 3-10-2008 J. Menten1 Belgian Breast MeetingProf Dr J Menten Radiation-Oncology Brussels 3-10-2008 Coordinator palliative Care Breast Cancer: comfort.

Documents

pain treatment slide

continuous pain

total pain

pain prevalence

management of cancer

art of cancer pain treatment

diagnosis of cancer

cancer diagnosis