Transcript “Comprehensive cancer pain management “ ECCO

Breast Cancer: comfort therapy
Belgian Breast Meeting
Brussels 3-10-2008
Prof Dr J Menten
Radiation-Oncology
Coordinator palliative Care
BBM 3-10-2008 J. Menten
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Breast cancer:
1 Pain treatment
2 Co-analgesics
3 Adjuvant medication
4 Advance care planning
BBM 3-10-2008 J. Menten
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A
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Pa
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Ce
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n=4947
Pain is the key symptom
Symptoms leading to diagnosis 31%
31%
leading to cancer diagnosis
1% 1% 1% 1% 1% 1% 1% 1% 1% 1% 1%
27%
followed by a lump and chronic fatigue
11%
9%
7%
5%
2% 2% 2% 2% 2%
3%
4%
5% 5%
BBM 3-10-2008
J. Menten
S3. What symptoms
lead you to see the doctor prior to your diagnosis of cancer? 3
Base: all who has specified cancer (n=4947)
HCP with main responsibility for management of cancer pain
Other; 5%
Radiation Oncologist; 1%
Physiotherapist; 1%
None; 3%
Anaesthetist; 1%
Nurse/Specialist Nurse; 1%
Neurologist; 2%
OB/GYN; 2%
Palliative care physician; 2%
Pain Specialist; 3%
Medical Oncologist; 42%
Oncologist
42%
Haematologist; 4%
General Surgeon; 4%
Medical Doctor; 9%
Base: (n=573)
General practitioner 19%
General/Family Practitioner;
19% J. Menten
BBM 3-10-2008
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PAIN PREVALENCE
Oncological patients
100 %
30%
curative therapy
60%
80 to 90%
palliative care
0
Diagnosis
Pain Treatment
BBM 3-10-2008 J. Menten
Death
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% of patients reporting pain in cancer
56%
56%
Global (n=5084)
65%
UK (n=617)
Sw itzerland (n=267)
Sw eden (n=1051)
75%
20%
20%
61%
Rom ania (n=327)
Norw ay (n=302)
88%
66%
Italy (n=457)
88%
71%
Israel (n=287)
52%
Ireland (n=96)
France (n=642)
62%
52%
Finland (n=383)
54%
Denm ark (n=373)
Czech Republic (n=282)
0%
71%
10%
20%
30%
40%
50%
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60%
70%
80%
90%
100%
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Strong opioids in elderly palliative patiënts
Menten & al. J Current med opinion, 2002
Mean dose TTS-fentanyl in function of tumortype
250
Mean TTS-fentanyl dose
(µg/h.+/- SD)
200
116
+600 mg p.o.morfine equivalence/d
65
150
100
+200 mg p.o.morfine equivalence/d
50
0
Basis
Lung
Lung
M1
M2
M3
Prostate
Prostate
Each point concerns ≥ 20 patiënten
M4
Breast
Breast
M5
M6
Eindp
Gastro-intestinal
Gastro-Intestinal
PAIN
Psychological
Physical
Total Pain
(C. Saunders)
Social
Suffering
Spiritual
Interdisciplinary approach!!!
1 Pain: Opioids & life expectancy?
Median survival in home care in
function of daily morphine dose
40
35
30
25
20
15
10
5
0
not
P = 0,002 Mantel-Cox
5-299
300-599
>600
morphine mg/day
P=0,029 Breslow-analysis
Bercovitch et al. Cancer 2004; 101 (6):1473-7
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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-13
J. Menten, Leuven, Belgium
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
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, Belgium
2 Co-analgesics
All Oncologists:
:
1-NSAID’s
2-Corticosteroids
3-Antidepressants
Neuropathic pain
4-Anticonvulsants
5-Bisphosphonates
Expert advice:
-topical therapies
-NMDA-receptor antagonists
-α-2 Adrenergic or GABA-agonists
-Neuroleptics (neuropathic pain)
-Benzodiazepines (paroxysmal neuropathic pain)
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
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
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
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!!
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
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
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
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
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
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
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
Multiple Event Analysis (adapted from Rosen et al., Cancer 2003)
Zoledronic acid 4 mg significantly decreases the risk of
developing a skeletal complication (16% reduction)
Hazard
ratio
Multiple
myeloma
P value
0.932
.593
Breast
cancer
0.799
.025
Total
0.841
.030
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Hazard ratio (Zole 4 mg versus Pam)
In favor of Zole
In favor of Pam
*Hypercalcemia of malignancy is included as an SRE.
1.8
2
Intravenous Ibandronate significantly reduces
skeletal morbidity
2.0
SMPR= skel.morbidity period (12w) rate
Placebo
Bondronat 6mg
SMPR: 1.48 vs 1.19, p=0.004
Mean SMPR
1.5
p=0.004
p=0.011
1.0
p=0.023
p=0.396
p=0.075
0.5
0
Body JJ, et al. Ann Oncol 2003
Trial not powered for individual
composite endpoints
Effects on pain (VAS)
(mean ± SEM)
VAS 7
6
5
*
4
*
*
3
2
1
0
07
21
42
Days
Mancini I, Body JJ; JCO 2004
Bisphosphonates for metastatic breast cancer
- WHEN TO START? (from Hillner et al., ASCO 2003 update, JCO 2003)
 evidence of bone destruction on imaging
only abnormal bone scan : « not recommended »
? WHEN TO STOP ???
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
Systemic treatment of bone metastases
General principles:
-Look to response rates, to survival, ... to “Quality of Life”
-“listen to the patient”,has the patient benefit from the therapy ?
Clinical improvement, no radiological response
continue
If there is clear radiological response but:
- no “symptom” benefit for the patient
stop ?
- intractable treatment related adverse effects
that give more burden than the disease
stop treatment
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Systemic treatment of bone
metastases
General principles:
-For bone metastases there is frequently pain control
in the absence of measurable tumor regression.
-No pain control, but other clear benefit of the treatment:
“treat the pain”: radiotherapy, analgesics,
NSAID’s, biphosphonates, …ask advice…interdisciplinarity !
-Oncological treatment
Palliative treatment  palliative care
BBM 3-10-2008 J. Menten
Teamwork
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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, Belgium
3 Adjuvant medication:
- have no intrinsic or indirect analgesic effect
- counteract the side effects of analgesics
-constipation
-nausea & vomiting
-sedation
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, Belgium
Adjuvant drugs
Laxatives
All patients taking strong opioids regularly
will develop constipation !!
-Prophylactic laxatives: always!
R/osmotic laxatives
contact laxatives
clysma
Educational Symposium: “Comprehensive cancer pain management “ ECCO-13
J. Menten, Leuven, Belgium
Adjuvant drugs
Anti-emetics
-Make
them available ….but start them when You
start strong opioids and taper the dose when
possible
Somnolence
-after opiodsdisappears spontaneously after 24 – 48 h
-Exceptionally: Methylfenidate (Rilatine®) 5 + 5 mg
The role of adjuvant medication
in metastatic breast cancer
We have for metastatic breast cancer patients :
–
–
–
–
–
5-0H-T3 receptor antagonist (anti-emetics)
hematopoietic growth factors
recombinant erythropoietin
low molecular weight heparin
biphosphonates
Each of them :
– is very expensive
– does not improve survival
– is given to improve quality of life
Cost effectiveness?
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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
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Medicinal cannabis and cancer
palliation
Cannabis Sativa plant
Cannabinoid
Registered
name
Route of
administration
Indications
Firm
Legal status
Solvay
Pharmaceuticals
(Marietta, GA,
US)
FDA approval
April 2003
Valeant
Pharmaceuticals
(Aliso Viejo, CA,
US)
FDA approval
May 2006
Anorexia / weight
loss (aids)
Dronabinol
(synthetic
THC)
Nabilone
(dronabinol
analogue)
THC & CBD
(isolated
from
Cannabis
Sativa L.)
Marinol®
Cesamet®
Sativex®
Nausea and
vomiting
(Cancer)a
Oral
Nausea and
vomiting
(Cancer)a
Oral
Sublingual
Symptomatic relief
of neuropathic pain
(MS)
GW
Pharmaceuticals
(Salisbury, UK)
Approval
NOC/c
policy in
Canadab
Limited
availability
in Spain and
UK
Abbreviations: THC, Δ9-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.
Engels K; de Jong A. et al. Medicinal cannabis in oncology. European journal of cancer 43 (2007) 2638-2644.
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Legal Dutch medicinal cannabis
Since Sept 2003 available for clinical
research, drug formulation development and
on prescription for patients
3 medicinal Cannabis Flos varieties:
Bedrocan®, Bedrobinol® and Bediol® to
make thee of or to inhal
41.25 Euro – 43.50 Euro per 5g ~10 doses
(expensive – not reïmbursed)
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Medical use in oncology
(delayed or anticipatory) chemo- or radiotherapy
induced nausea and vomiting
Nabilone may have a role in patients whose nausea and emesis is not
adequately controlled by 5-HT3 receptor agonists and Emend® and may
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
Manag. 2008 February; 4(1):99-107
Cancer-associated anorexia
Insomnia relief
Mood elevation
Appetite stimulation
Analgesia : equal analgesic effect to codeine or 20 mg morphine/d.
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Side effects
Narrow therapeutic window
Acute psychoactive effects: dizziness,
dysphoria, depression, hallucinations and
paranoia
Impaired psychomotor function
Potential synergistic effects with other
psychotropic agents and alcohol
Risk of developing dependence
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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%
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4 Advance directive planning
-Inform the patient progressively
-Define realistic goals
-Discuss what has to be done if treatment fails
-Supportive therapy  palliative care
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Impact of respons on QoL: breastca
CR/PR
SD
PD
% patients with symptom control in relation
to obj tumour respons
Geels et al, J Clin Oncol 2000
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Conclusion
6-Stervensproces
-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
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