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

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Presentation on theme: "BBM 3-10-2008 J. Menten1 Belgian Breast MeetingProf Dr J Menten Radiation-Oncology Brussels 3-10-2008 Coordinator palliative Care Breast Cancer: comfort."— Presentation transcript:

1 BBM J. Menten1 Belgian Breast MeetingProf Dr J Menten Radiation-Oncology Brussels Coordinator palliative Care Breast Cancer: comfort therapy

2 BBM J. Menten 2 Breast cancer: 1 Pain treatment 2 Co-analgesics 3 Adjuvant medication 4 Advance care planning

3 BBM J. Menten 3 Symptoms 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 Pain is the key symptom leading to cancer diagnosis followed by a lump and chronic fatigue 31%

4 BBM J. Menten 4 HCP with main responsibility for management of cancer pain Base: (n=573) Oncologist 42% General practitioner 19%

5 BBM J. Menten 5 palliative therapy palliative care Oncological patients 100 % 0 curative therapy DiagnosisDeath 30% 60 % PAIN PREVALENCE 80 to 90% Pain Treatment

6 BBM J. Menten 6 % of patients reporting pain in cancer 56% 20% 88%

7 Strong opioids in elderly palliative patiënts Menten & al. J Current med opinion, 2002 Each point concerns ≥ 20 patiënten LungProstateBreastGastro-Intestinal Mean dose TTS-fentanyl in function of tumortype +200 mg p.o.morfine equivalence/d +600 mg p.o.morfine equivalence/d

8 Total Pain (C. Saunders) Physical Spiritual Psychological Social Suffering PAIN Interdisciplinary approach!!!

9 BBM J. Menten 9 1 Pain: Opioids & life expectancy? Patterns of high-dose morphine use in a home- care hospice service: should we be afraid of it? Bercovitch m., Adunsky A. (Tel Hashomer Hospice, Chaim Sheba Med Center, Tel Hashomer, Israël) Cancer 2004; 101 (6): But we are all afraid!!!

10 BBM J. Menten 10 P = 0,002 Mantel-Cox P=0,029 Breslow-analysis Bercovitch et al. Cancer 2004; 101 (6): Pain: Opioids & life expectancy?

11 Educational 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

12 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

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

14 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 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

15 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!!

16 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

17 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 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

18 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

19 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.030 Total Breast cancer Multiple myeloma *Hypercalcemia of malignancy is included as an SRE. Hazard ratio Zoledronic acid 4 mg significantly decreases the risk of developing a skeletal complication (16% reduction)

20 Intravenous Ibandronate significantly reduces skeletal morbidity Mean SMPR All new bone events Vertebral fractures Non-vertebral fractures Need for radiotherapy Need for surgery 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 individual composite endpoints Body JJ, et al. Ann Oncol 2003 SMPR= skel.morbidity period (12w) rate

21 Effects on pain (VAS) (mean ± SEM) Days Mancini I, Body JJ; JCO * * * VAS

22 (from Hillner et al., ASCO 2003 update, JCO 2003) Bisphosphonates for metastatic breast cancer - WHEN TO START? -  evidence of bone destruction on imaging  only abnormal bone scan : « not recommended »

23 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 ???

24 BBM J. Menten 24 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

25 BBM J. Menten 25 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 Palliative treatment  palliative care Teamwork

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

27 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

28 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

29 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®) mg

30 BBM J. Menten 30 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?

31 BBM J. Menten 31 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

32 Medicinal cannabis and cancer palliation Cannabis Sativa plant

33 BBM J. Menten 33 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) CannabinoidRegistered name Route of administration IndicationsFirmLegal status Dronabinol (synthetic THC) Marinol ® Oral Anorexia / weight loss (aids) Nausea and vomiting (Cancer) a a Solvay Pharmaceuticals (Marietta, GA, US) FDA approval April 2003 Nabilone (dronabinol analogue) Cesamet ® Oral Nausea and vomiting (Cancer) a a Valeant Pharmaceuticals (Aliso Viejo, CA, US) FDA approval May 2006 THC & CBD (isolated from Cannabis Sativa L.) Sativex ® Sublingual Symptomatic relief of neuropathic pain (MS) GW Pharmaceuticals (Salisbury, UK) Approval NOC/c policy in Canada b b Limited availability in Spain and UK

34 BBM J. Menten 34 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 Euro – Euro per 5g ~10 doses (expensive – not reïmbursed)

35 BBM J. Menten 35 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. 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 February; 4(1): Ware M. et al. A review of nabilone in the treatment of chemotherapy induced nausea and vomiting. Ther Clin Risk Manag February; 4(1): Cancer-associated anorexia Insomnia relief Mood elevation Appetite stimulation Analgesia : equal analgesic effect to codeine or 20 mg morphine/d.

36 BBM J. Menten 36 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

37 BBM J. Menten 37 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%

38 BBM J. Menten 38 4 Advance directive planning - Inform the patient progressively -Define realistic goals -Discuss what has to be done if treatment fails -Supportive therapy  palliative care

39 BBM J. Menten 39 % 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

40 BBM J. Menten 40 6-Stervensproces Conclusion -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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