Breast Cancer comfort therapy Belgian Breast Meeting Brussels
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 1
Breast cancer: 1 Pain treatment 2 Co-analgesics 3 Adjuvant medication 4 Advance care planning BBM 3 -10 -2008 J. Menten 2
n=4947 Pain is the key symptom Symptoms leading to diagnosis 31% leading to cancer diagnosis followed by a lump and chronic fatigue Base: all who has specified cancer (n=4947) BBM 3 -10 -2008 J. Menten S 3. What symptoms lead you to see the doctor prior to your diagnosis of cancer? 3
HCP with main responsibility for management of cancer pain Oncologist 42% Base: (n=573) General practitioner 19% BBM 3 -10 -2008 J. Menten 4
PAIN PREVALENCE Oncological patients 100 % 30% curative therapy 60% y p a r e h t e palliativ 80 to 90% palliative care 0 Diagnosis Pain Treatment BBM 3 -10 -2008 J. Menten Death 5
% of patients reporting pain in cancer 56% 20% 88% BBM 3 -10 -2008 J. Menten 6
Strong opioids in elderly palliative patiënts Menten & al. J Current med opinion, 2002 Mean dose TTS-fentanyl in function of tumortype 116 +600 mg p. o. morfine equivalence/d 65 +200 mg p. o. morfine equivalence/d Lung Prostate Each point concerns ≥ 20 patiënten Breast BBM 3 -10 -2008 J. Menten Gastro-Intestinal
PAIN Psychological Physical Total Pain (C. Saunders) Social Suffering Spiritual Interdisciplinary approach!!! BBM 3 -10 -2008 J. Menten
1 Pain: Opioids & life expectancy? P = 0, 002 Mantel-Cox P=0, 029 Breslow-analysis Bercovitch et al. Cancer 2004; 101 (6): 1473 -7 BBM 3 -10 -2008 J. Menten 10
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 3 -10 -2008 management. J. “ Menten ECCO-13 BBM J. Menten, Leuven, Belgium 11
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 BBM 3 -10 -2008 J. Menten 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 Neuropathic pain 5 -Bisphonates 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 BBM 3 -10 -2008 J. Menten
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 BBM 3 -10 -2008 J. Menten
Co-analgesics 2 Corticosteroids -high doses (>6 mg dexamethasone, >32 mg 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 BBM 3 -10 -2008 J. Menten
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 BBM 3 -10 -2008 J. Menten
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 BBM 3 -10 -2008 J. Menten
Co analgesics 5 Bisphonates 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 BBM 3 -10 -2008 J. Menten
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 (12 w) rate SMPR: 1. 48 vs 1. 19, p=0. 004 Mean SMPR 1. 5 p=0. 004 1. 0 p=0. 011 p=0. 396 p=0. 023 p=0. 075 0. 5 Body JJ, et al. Ann Oncol 2003 e su ed rg fo er r y N N e th ed er fo ap r y io ra d fr erte ac b tu ra re l s -v on N Ve fr rte ac b tu ra re l s bo ne Al e l n ve ew nt s 0 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
Bisphonates 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 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 BBM 3 -10 -2008 J. Menten 24
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 25
Co-analgesics Bisphonates 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 bisphonates combined with -dental extractions or surgical interventions of the jaws -chemotherapy -corticosteroids Educational Symposium: “Comprehensive cancer pain management “ ECCO-13 J. Menten, Leuven, Belgium BBM 3 -10 -2008 J. Menten
3 Adjuvant medication: - have no intrinsic or indirect analgesic effect - counteract the side effects of analgesics -constipation -nausea & vomiting -sedation BBM 3 -10 -2008 J. Menten 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 BBM 3 -10 -2008 J. Menten
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 BBM 3 -10 -2008 J. Menten
The role of adjuvant medication in metastatic breast cancer We have for metastatic breast cancer patients : – – – 5 -0 H-T 3 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? BBM 3 -10 -2008 J. Menten 30
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 BBM 3 -10 -2008 J. Menten 31
Medicinal cannabis and cancer palliation Cannabis Sativa plant BBM 3 -10 -2008 J. Menten
Cannabinoid Registered name Route of administration Indications 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 Sublingual Symptomatic relief of neuropathic pain (MS) Firm Legal status Solvay Pharmaceuticals (Marietta, GA, US) FDA approval April 2003 Valeant Pharmaceuticals (Aliso Viejo, CA, US) FDA approval May 2006 GW Pharmaceuticals (Salisbury, UK) Approval NOC/c policy in Canadab Limited availability in Spain and UK Abbreviations: THC, Δ 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. Engels K; de Jong A. et al. Medicinal cannabis in oncology. European journal of cancer 43 (2007) 2638 -2644. BBM 3 -10 -2008 J. Menten 33
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 5 g ~10 doses (expensive – not reïmbursed) BBM 3 -10 -2008 J. Menten 34
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 -HT 3 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. BBM 3 -10 -2008 J. Menten 35
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 BBM 3 -10 -2008 J. Menten 36
4 Advance directive planning How long do we continue with anticancer treatment As long as treatment is effective Untill available drugs have been used As long as the patient asks for therapy As long as the PS ≥ 70% BBM 3 -10 -2008 J. Menten 37
4 Advance directive planning -Inform the patient progressively -Define realistic goals -Discuss what has to be done if treatment fails -Supportive therapy palliative care BBM 3 -10 -2008 J. Menten 38
Impact of respons on Qo. L: breastca CR/PR SD PD % patients with symptom control in relation to obj tumour respons Geels et al, J Clin Oncol 2000 BBM 3 -10 -2008 J. Menten 39
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 BBM 3 -10 -2008 J. Menten 40
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