PALLIATIVE TREATMENT BY DR. KHRONGKAMOL SIHABAN MEDICAL ONCOLOGIST

PALLIATIVE TREATMENT BY DR. KHRONGKAMOL SIHABAN MEDICAL ONCOLOGIST

TREATMENT IN ONCOLOGY Main treatment : surgery Neoadjuvant treatment : RT, CMT Adjuvant treatment : Tx micrometastatic disease -CMT,Targeted therapy -RT -Hormone

TREATMENT IN ONCOLOGY Palliative treatment : quality of life, prolong life, relieve symptom -CMT, Targeted therapy -RT -Sx -Others -BSC

Treatment outline of early or locally advanced cancer Early or locally advanced cancer Primary treatment: surgery Neoadjuvant chemotherapy/ radiotherapy Adjuvant chemotherapy / radiotherapy Unresectable Surveillance Recurrent disease In remission

Treatment outline of advanced or metastatic cancer Advanced or metastatic cancer Resectable Unresectable Surgery Postoperative Chemotherapy/ radiotherapy Palliative chemotherapy/ radiotherapy Response Second-line Not response/ Too toxic Best supportive care

ASSESSMENT BY ONCOLOGY TEAM Benefits/Burdens of anticancer therapy - Natural of specific tumor - Potential for response to further treatment - Potential for treatment-related toxicities - Patient s understanding of disease prognosis - Goal and meaning of anticancer therapy for patient/family/caregivers - Impairment of vital organs - Performance status - Serious comorbid conditions

ASSESSMENT BY ONCOLOGY TEAM Patient/family/caregivers goals/values/expectations/priorities - Shared decision-making with patient/family/caregivers - Advance care planning - Goals and meaning of anticancer therapy - Quality of life

ASSESSMENT BY ONCOLOGY TEAM Symptom management - Pain - Dyspnea - Anorexia/cachexia - Nausea/vomiting - Constipation - Diarrhea - Etc.

DOMAINS FOR PAIN MANAGEMENT OUTCOME : 4 A s Analgesia Activities of Daily Living Adverse Events Aberrant Drug-Taking Behaviors

CANCER PAIN MANGEMENT STRATEGIES Pharmacologic strategies - Nonopioid analgesics - Acetaminophen - Nonsteroidal anti-inflammatory drugs - Opioid analgesics - Coanalgesics (adjuvant analgesics) Psychological strategies - Hypnosis or relaxation with imagery - Cognitive-behavioral methods

CANCER PAIN MANGEMENT STRATEGIES Physical strategies - Massage - Exercise - Transcutaneous electrical nerve stimulation (TENS) - Acupucture Nerve blocks Radiation therapy Chemotherapy

OPIOID ANALGESICS : CANCER PAIN Used most often in the management of severe pain : - Effectiveness - Ease of titration - Favorable risk-to-benefit ratio Routes of administration - Oral - Transdermal - Intraspinal : epidural or intrathecal

OPIOID FORMULATIONS TYPE OF DRUG Pure µ-opioid receptor agonists Dual mechanism opioids Rapid onset (transmucosal) Immediate release Modified release (long acting) Available with co-analgesic Only available with co-analgesic EXAMPLES Morphine, hydromorphone, fentanyl, oxycodone Tramadol, tapentadol Fentanyl, alfentanil, sufentanil, diamorphine Tramadol, oxycodone Morphine, methadone, oxycodone Oxycodone, tramadol, codeine Hydrocodone

Codeine natural opioid ADR : Constipation Onset Duration Dosage Ceiling dose Shift when 30 mins 4-6 hrs 30 60 mg PO q 4-6 hrs 120 mg/dose not response at 60 mg q 4 hrs

Tramadol synthetic opioid Action: MOPr and SNRI ADR : N/V, Dizziness Onset Duration 1 hr 8 hrs Dosage Ceiling dose Shift when 50 100 mg PO q 6-8 hrs 100 mg/dose not response at 400 mg/day

Morphine natural opioid Injection Oral Immediate release Controlled release Onset : IV < 5 mins MO IR 15 30 min MST 1 hr Kapanol 2-4 hr PotencyOral = 1/3 IV (1 st pass metabolism effect) Sustained release MST 10, 30 mg Extended release Kapanol 20, 50 mg

Oxycodone semisynthetic opioid Onset 15 min for IR, Stable over 12 hr for CR Initial dose 5 15 mg PO q 4-6 h (IR) 10 mg PO q 12 h (CR) Dosage 10-30 mg PO q 4-6 h (titrate up 25% q 12 hr for CR)

Fentanyl synthetic opioid Highly lipid soluble Onset Duration Prep. 12-24 hrs 72 hrs/patch 12, 25, 50 mcg/hr Initiation Naïve to opioid 12 25 mcg/hr Do not forget to prescribe bridging analgesics in first 12-24 hr

ADVERSE DRUG REACTION OF OPIOID ANALGESIC DRUGS

Skin Neuro GI ADVERSE REACTION of opioids usage Sedation Confusion Myoclonus Respiratory depression Nausea / Vomiting Constipation Itching Histamine release Dry lips Urinary retention

NEUROLOGICAL ADR of opioids usage Sedation Confusion Myoclonus Reduce 25% Methylphenidate IR Light Exposure T Reduce 25 % TCA LT ADR Baclofen, Valium Respiratory depression Naloxone 0.2 mg IV push q 2-3 min Dry mouth NaHCO 3 mouthwash 3-4 times/day T Urinary retention Foley s cath T. T = Tolerable ADR

GASTROINTESTINAL ADR of opioids usage Nausea / Vomiting Co-administration antiemetics Constipation Stimulant laxative Stool softener *** AVOID bulk forming *** T T = Tolerable ADR

OPIOID SWITCHING Opioid rotation ( or switching) is a change in opioid drug or route of administration with the goal of improving outcomes. Opioid therapy for acute or chronic pain requires individualization of the dose, with the objective of identifying a favorable balance between analgesia and side effects.

INDICATIONS FOR SWITCHING Occurrence of intolerable adverse effects during dose titration Poor analgesic efficacy despite aggressive dose titration Problematic drug-drug interactions Preference or need for a different route of administration Change in clinical status (e.g. concern about drug abuse) or clinical setting that suggests benefit from an opioid with different pharmacokinetic properties Financial or drug-availability considerations

STEP 1 : EFFICACY OPIOID ROTATION Calculate Equianalgesic dose (the dose in steady state provide the same analgesic response) Require special consideration MO (PO) MO (IV) Oxycontin Codeine Tramadol Fentanyl TTS Methadone IV 30 mg 10 mg 15 mg 200 mg 250 mg 12 mcg/hr 8 mg Methadone Oral 16 mg 1 x 1.5 x 20 x 25 x 1.2 x 0.8 x 3 1 1 x 2.

STEP 2 : SAFETY Pathogenesis : Variation of MOPr subtype in different person Identified Automatic Dose Reduction Windows ~ 25 50 % due to incomplete cross-tolerance 25 % in General population 50 % in currently on High dose Elderly/Frailty

STEP 3 : INDIVIDUALIZED Re-assessment Titration up 25% if inadequate Rescue dosing prescription 10 15 % (1/6 of total daily dose)

EXAMPLE A 56 years old female who has advance stage CA breast which currently on Kapanol (50) 2 tab PO at 8PM MST (10) 2 tab PO at 8AM MO IR (10) 2 3 tab per day Kapanol was sold out from hospital. So you need to change it to another drugs

EXAMPLE Step 1: Calculate MEDD [(100+20) 3] + [10x3 3] 40 + 10 50 mg of MO IV per day Step 2 : calculate ADRW

EXAMPLE Switch to Oxycontin 37.5 x 1.5 = 56.25 mg Order Oxycontin (30) 1 tab PO q 12 h

EXAMPLE Step 3: Breakthrough : 6.25 mg MO IR (10) 1 tab PO prn q 4-6h Reassessment If not adequate +25% (~9-10 MO equivalence)

Jirawat Thanestada, M.D. SUMMARY