Pocket Oncology (Pocket Notebook Series), 1st Ed.

NONPAIN SYMPTOM MANAGEMENT

Peter A. Forsberg and Tanya Nikolova

Nausea and Vomiting

• Antiemetic Rx- Select agent based on trigger & receptor as above. Start dosing as PRN & ↑ to standing if needed; if inadequate add agent from another class

• Medications (category: Agents + dosing & frequency all PRNs)

• 5HT3 antagonists, NK 1 antagonists & corticosteroids: Agents & doses in table below; note: Doses are generally lower outside setting of CINV or in less emetogenic regimens

• H1 antagonists: Promethazine 12.5 or 25 mg PO q4–6h

• Dopamine (D2) antagonists: Peripheral- Metoclopromide 5–20 mg IV/PO q4–6h. Central- Prochlorperazine 5–10 mg IV/PO q4–6h; Haloperidol 0.5–2 mg PO/IV q4–6h

• AchM antagonist (antiacetylcholine): Scopolamine 1.5 mg transdermal q72h

• 5HT2 antagonists: Olanzapine 2.5–5 mg PO q12–q24h

• Cannabinoids: Dronabinol 5–10 mg PO q6h; Nabilone 1–2 mg PO bid

• BDZ: Lorazepam 0.5–2 mg IV or PO q4–6h

• Chemotherapy-induced N/V- 3 distinct types: Acute, delayed, & anticipatory. Acute begins 1–2 h after chemotherapy & peaks at 4–6 h, delayed begins at 24 h & peaks at 48–72 h, anticipatory is conditioned response to nausea a/w previous cycles of chemotherapy

• Classifying risk of CINV- Based on % frequency of associated nausea/emesis chemotherapeutic agents are classified into risk classes:

• High risk: >90%; common agents: CIS, high-dose Cyclophosphamide

• Mod. risk: <90% & >30%; eg, Doxorubicin, low-dose Cyclophosphamide

• Low risk: <30% & >10%; eg, Docetaxel, Trastuzumab, GEM

• Min. risk: <10%; eg, Vincristine, rituximab

Constipation

• Frequency- Affects 50% of pts w/advanced CA; majority of pts being treated w/opioid analgesics, other contributants: Malig/obstruction, ↓ PO/fluid intake, inactivity, anticholinergics, electrolyte derangement

• Goal is 1 unforced BM every 1–2 d; should prophylax when opiates started

• Evaluation- R/o obstruction, impaction if present consider glycerol suppos or disimpaction

• Tx- Nonpharm as able: ↑ fluid intake, ↑ activity, fiber supplement or bulk-forming laxative (eg, Metamucil)

• Pharm (initial): Stimulant laxative ± stool softener; eg, Senna 1–2 tabs (8.6–15 mg) qhs or Bisacodyl 5–15 mg ± Docusate 30 mg/d

• Step up Rx- Add on to initial w/osmotic laxative- Polyethylene glycol 17 gm/d (max 34 gm/d), Lactulose 15–30 gm PO q6h PRN, Magnesium hydroxide or Magnesium citrate or per rectal Rx eg, Bisacodyl 10 mg suppos

• If opioid-related constipation doesn’t respond to standard Rx consider adding Methylnaltrexone 0.15 mg/kg SC every other d (N Engl J Med 2008;358:2332); must r/o obstruction before initiating methylnaltrexone

Anorexia/Cachexia Syndrome

• Definitions: Anorexia- loss of appetite & ↓ caloric intake

• Starvation- loss of wt w/relative preservation of muscle mass until end stages

• CA Cachexia Syndrome- multifactorial syndrome defined by loss of skeletal muscle mass that can’t be fully reversed by nutritional support → progressive functional impairment (Lancet Oncol 2011;12(5):489)

• Pathophysiology- chronic inflammation w/↑ cytokine activity (TNFα, IL-1β, IL-6) → dysregulated metabolism w/↑ proteolysis & ↓ appetite

• Dx- ≥10% involuntary wt loss or ≥2% wt loss in pt w/initial BMI <20 or muscle wasting

• Evaluation- assess for reversible contributants incl pain, nausea, constipation/bowel obstruction, mucositis, xerostomia, oral candidiasis, depression, anxiety, & delirium

• Tx- nutritional counseling, dietary & modular nutritional supplementation, exercise program

• Pharm- appetite stimulants:

• Corticosteroids: Dexamethasone 4–8 mg/d or prednisone 20–40 mg/d- Use & benefit limited by SE w/long-term use, indicated primarily for short courses (<6 wks) in advanced disease

• Progesterone analogs: Megestrol acetate 400–800 mg/d (more efficacious in higher)- Appetite ↑ in approx 1 wk, wt gain takes several wks; fewer SE than steroids w/similar efficacy, include ↑ risk of thromboembolic disease, suppression of hypothalamic-pituitary axis if stressed

• Cannabinoids: Dronabinol- Leads to ↑ appetite, less wt gain, SE include sedation & confusion

• Others/investigational: Thalidomide, anabolic steroids (Oxandrolone), NSAIDs, Omega-3 fish oils, psych meds (Mirtazapine, Olanzapine)

• No evidence for prophylactic use of any pharmacologic agents

Dyspnea

• Etiology- Often multifactorial, various causes: Space-occupying masses or pleural effusions, anemia, comorbid COPD or CHF, PE, PNA, hypoxia or hypercarbia, thick secretions & respiratory muscle weakness

• Tx- Initial approach is target-specific etiologies & direct Rx to these eg, thoracentesis for pleural effusion, bronchodilators for bronchospasm

• Supplemental O2- Clear utility in hypoxia, in nonhypoxic pts may have some benefit but no more efficacious than room air by NC

• Pharm- For 1° tx of dyspnea in advanced disease:

• Opioids- 1st line Rx for dyspnea

• Initial doses: Opiate naïve pt- PO Morphine sulfate 2.5–5 mg every 4 h or equivalent (see table in pain management section)

• If opioid tolerant use efficacious dose of currently used opiate

• If dyspnea intermittent use PRN, if constant use scheduled around the clock dosing

• Titrate dosing by 25–50% every 12–24 h until efficacious dose reached & titrate frequency as needed

• Benzodiazepines- 2nd line Rx, 1° efficacy is in combination w/opiates. For intermittent use short-acting benzo (eg, Lorazepam 0.5–1 mg PO q6h) for persistent consider LA (eg, Clonazepam 0.25 mg q12h)

Fatigue

• Prevalence/screening- Occurs in up to 75% of all solid tumor pts & up to 99% of CA pts receiving multimodality Rx. Providers should screen for fatigue at initial visit, at dx of advanced disease & w/each chemo visit; should assess for depression & insomnia w/new dx of fatigue (J Clin Oncol 2008;23:3886)

• Tx- Cognitive-behavioral Rx incl teaching & counseling, education, exercise (unless contraindicated)

• Pharm- Stimulants: Use should be limited to pt’s w/mod.-to-sev. fatigue when nonpharm methods unsuccessful

• Methylphenidate- Initial dose 5–10 mg PO in AM ± 5 mg at noon

• Modafinil- 200 mg in AM ± 100 mg at noon (max 400 mg/d)

• Corticosteroids- Used primarily in setting of further sx, incl anorexia or nausea

• Several common 2° causes to eval & target include anemia (most common), thyroid or adrenal insuff, hypogonadism

Delirium

• Definition- Disturbances in level of consciousness, attention, cognition and/or perception developing abruptly w/fluctuations over course of d

• Clinical subtypes- Hyperactive, hypoactive, & mixed

• Identify & treat reversible causes incl prev EtOH or drug use (withdrawal syndromes); meds esp. opioids, BDZ, & anticholinergics; infxn, dehydration, hypoxia or hypercarbia or electrolyte disturbance (↑ Ca)

• Tx- Correct identified contributants as able then target sx

• Maximize nonpharm intervention prior to pharmacology including reorientation, cognitive stimulation, sleep hygiene, early mobilization, bowel & bladder monitoring, etc.

• Use of antipsychotics should be geared toward short-term use for acute sx

• Benzodiazepines should only be initiated for delirium as an adjunct to antipsychotics in setting of agitation despite adequate antipsychotic dosing (J Clin Oncol 2011;30:1206)