Symptom Control in Patients with Cancer¶
Chapter 74 | Part 4: Oncology and Hematology · Part 4 – Oncology: Solid Tumors · Chapter 74
Key Clinical Points¶
- Prompt symptom assessment improves survival in metastatic cancer patients (Basch et al.).
- PROs (e.g., ESAS–FS) enhance quality of life and median overall survival (31.2 vs 26 months).
- Structured exercise (45 min walking daily) is a primary intervention for fatigue.
- Bupropion reduces fatigue with minimal side effects; Olanzapine is first-line for anorexia without serious harm.
- Duloxetine is the only proven treatment for CIPN.
- Fezolinetant (NK3 receptor antagonist) treats hot flashes in women as a nonhormonal option.
- Immunotherapy risks: Hypothyroidism (5–22%) and hypophysitis (1–2%).
- Nasal vestibulitis affects up to 75% of patients on taxanes/bevacizumab.
- High-dose steroids for dyspnea require monitoring for hyperglycemia, immunosuppression, and osteoporosis.
- Olanzapine is the most effective component in a four-drug cocktail for chemotherapy-induced nausea.
1. DEFINITION & OVERVIEW¶
Symptom control is critical in oncology care, particularly for metastatic cancer patients.
• Immunotherapy Complications: ◦ Hypophysitis: Occurs de novo in 1–2% of patients. ◦ Hypothyroidism: Occurs in 5–22% (average 6%) of patients; may manifest 6–8 weeks post-immunotherapy or later.
• Initial Assessment Priorities: ◦ Screen for: Hypothyroidism, anemia, hypercalcemia, electrolyte abnormalities, and renal failure. ◦ Screening for depression/demoralization is essential.
• Intervention Strategies: ◦ Simple interventions: Correcting anemia, hypothyroidism, or electrolytes. ◦ Exercise: Structured exercise (e.g., 45 min walking daily) prevents/treats fatigue; clinicians should advise resuming the patient's prior exercise regimen rather than prescribing new ones. ◦ Pharmacotherapy for Fatigue: Methylphenidate (5 mg at 7/11 a.m. for 48 h); Bupropion (minimal side effects); Dexamethasone (8 mg daily, monitor for hyperglycemia).
• Assessment Tools: ◦ PRO scales like ESAS–FS are essential for multidimensional symptom assessment.
2. EPIDEMIOLOGY¶
Symptoms are prevalent across cancer populations:
• Fatigue: 70–80% prevalence (most common symptom). • Pain: 40–70% overall; frequently feared by patients. • Nausea/Vomiting: ◦ Chemotherapy-induced: 10–90% (common with cisplatin/doxorubicin). ◦ Non-chemotherapy: Common with bowel obstruction or opioids. • Anorexia/Cachexia: 20–80% prevalence (highest in lung/pancreatic cancers). • Dyspnea: 10–80% lifetime prevalence; more common near end-of-life. • Hot Flashes: ◦ 66% of breast cancer patients on tamoxifen. ◦ 75% of prostate cancer patients on androgen deprivation. • Nasal Vestibulitis: Up to 75% in taxane/bevacizumab recipients. • Oral/GI Toxicity: 30–40% depending on agents (e.g., doxorubicin, palbociclib). • CIPN: Affects majority of patients on neurotoxic chemotherapy.
Symptom Prevalence and Causes¶
Table 74-1 details symptom prevalence and associated causes:
• Fatigue: 70–80% (Chemotherapy; Immunotherapy). • Pain: 40–70% (Nociceptive: Pancreatic; Visceral: Obstruction; Neuropathic: CIPN; Incident: Bone metastases). • Oral/GI Toxicity: 30–40% (Doxorubicin, Palbociclib, Everolimus). • Nausea: 10–90% (Cisplatin, Doxorubicin). • Anorexia/Cachexia: 20–80% (Lung/pancreatic cancers). • Dyspnea: 10–80% (Lung cancer; Effusions; Pulmonary metastases). • Hot Flashes: 66–75% (Tamoxifen; Androgen deprivation). • Nasal Vestibulitis: Up to 75% (Taxanes, Bevacizumab).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Underlying mechanisms for common symptoms:
• Fatigue: Caused by cancer, hypercalcemia, anemia, hypothyroidism, chemotherapy, or immunotherapy. • Pain Types: ◦ Nociceptive: Pressure on nerves (e.g., pancreatic). ◦ Visceral: Distention of hollow viscus (e.g., obstruction). ◦ Neuropathic: Direct nerve damage (e.g., CIPN). ◦ Incident: Pathologic fractures/bone damage. • Nausea/Vomiting: Caused by chemotherapy, bowel obstruction, opioids, radiation, electrolyte imbalances, or cerebral metastases. • Anorexia/Cachexia: Driven by cancer hormones, drug treatments, mechanical difficulties, and food insecurity; characterized by muscle/adipose loss, metabolic imbalance, BMI <20, and sarcopenia. • CIPN: Caused by taxanes/platinums leading to nerve damage (numbness, tingling, burning). • Mucositis: ◦ Oral: 30–40% in patients on regorafenib/sorafenib/palbociclib/doxorubicin. ◦ GI: 50–80% with chemotherapy-induced diarrhea (tyrosine kinase inhibitors, everolimus). • Nasal Vestibulitis: Caused by chemotherapy damage to nasal epithelium leading to dryness/cracking/infection.
Types of Pain¶
Table 74-2 categorizes pain types:
• Nociceptive: Deep, dull, aching; constant and worsening with time (e.g., pancreatic cancer). • Visceral: Cramping, bloating; intermittent (e.g., intestinal obstruction). • Neuropathic: Sharp shooting, burning, allodynia/hyperalgesia (e.g., CIPN). • Incident: Minimal at rest, but excruciating with movement (e.g., bone metastases).
4. CLINICAL FEATURES¶
Assessment protocols for clinical evaluation:
• Fatigue: Use 0–10 rating for best/worst/average pain; identify acceptable score threshold. • Pain: Review prior treatments (e.g., acupuncture, medications). • Anticoagulant use: Screen for NOACs. • Nausea/vomiting: Patient/family interview regarding symptoms. • Anorexia: Direct inquiry about appetite. • Cachexia: Assess fatigue, anorexia, CRP elevation, BMI <20, and sarcopenia on CT. • Dyspnea: Rule out reversible causes (hypoxia, pneumonia, PE, effusion, COPD). • Hot flashes: Evaluate frequency/severity/impact on life in breast/prostate cancer patients. • Nasal vestibulitis: Assess for dryness, bleeding, crusting; confirm with exam. • Constipation: Review bowel habit history; >3 days since last BM = likely constipation. • CIPN: Evaluate timeline and drug exposure (e.g., taxanes). • Mucositis: Check for thrush, aphthous ulcers, herpes infections.
5. DIFFERENTIAL DIAGNOSIS¶
Differential considerations for common symptoms:
• Pain: Differentiate Nociceptive vs visceral vs neuropathic vs incident. • Nausea/vomiting: Distinguish Chemotherapy vs bowel obstruction/opioids/radiation/electrolyte imbalances/post-anesthesia/cerebral metastases. • Dyspnea: Rule out Cancer/radiation/chemotherapy/immunotherapy/COPD/asthma/bronchial constriction. • Anorexia: Differentiate Cancer hormones vs drug treatments/radiation/mechanical difficulties/food insecurity. • Cachexia: Multifactorial (weight loss, metabolic imbalance, reduced intake). • Mucositis: Distinguish Oral vs GI; identify drug-specific causes (fluorouracil/doxorubicin/tyrosine kinase inhibitors). • Nasal vestibulitis: Identify Taxanes/bevacizumab/chemotherapy-induced epithelial damage. • CIPN: Differentiate Chemotherapy agents (taxanes, platinums) vs other causes. • Incident pain: Distinguish Pathologic fractures/bone damage from residual cancer effects.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic approaches:
• Initial Screening: ◦ Check for: Hypothyroidism, anemia, hypercalcemia, electrolyte abnormalities, and renal failure. • Psychological Assessment: ◦ Screen for depression/demoralization. • Symptom Quantification: ◦ Use PRO scales (e.g., ESAS–FS) to assess 12 domains (pain, fatigue, nausea, etc.) on a 0–10 scale. • Cachexia Identification: ◦ Confirm via: 5–10% weight loss; BMI <20; sarcopenia on CT scan. • CIPN Assessment: ◦ Evaluate for Duloxetine benefit (0.6–1.0 point reduction on a 0–10 scale). • GI Mucositis Management: ◦ Loperamide (up to 24 mg/day); octreotide (300 mg/day) for refractory cases; glucocorticoids. • Dyspnea Assessment: ◦ Supplemental oxygen for SpO2 ≤90%; HFNO as bridge to other therapies.
Diagnostic Criteria and Scales¶
• Edmonton Symptom Assessment System–Revised (ESAS–FS): Multidimensional tool assessing 12 domains (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, well-being, sleep, financial distress, spiritual pain) on a 0–10 scale. • Cachexia Criteria: 5–10% weight loss; BMI <20; sarcopenia on CT scan.
7. MANAGEMENT & TREATMENT¶
Treatment strategies:
- Fatigue Management: • Identify/correct reversible causes → anemia, hypothyroidism, electrolytes. • Exercise: Prescribe structured 45 min walking daily; advise resuming prior exercise regimen. • Pharmacotherapy: Methylphenidate (5 mg at 7/11 a.m. for 48 h); Bupropion; Dexamethasone (8 mg/day).
- Pain Management: • Nociceptive: Acetaminophen → NSAIDs → opioids (with constipation prevention). • Visceral: NSAIDs/gabapentin/pregabalin + opioids; octreotide for malignant bowel obstruction. • Neuropathic: Duloxetine (moderately effective); gabapentin/pregabalin; opioids (equally effective as gabapentin/nortriptyline). Note: 3–4 weeks required to assess efficacy. • Incident pain: Low-dose gabapentin (100–200 mg TID) + opioids.
- Nausea and Vomiting Management: • Chemotherapy-related: Dexamethasone, 5-HT3 antagonists, NK1 antagonists, olanzapine (most effective). A four-drug cocktail is often used. • Non-chemotherapy: Olanzapine 5 mg/day.
- Anorexia and Cachexia Management: • Olanzapine 2.5 mg nightly (60% weight gain vs 9% placebo).
- Dyspnea and Hot Flashes Management: • Dyspnea: Supplemental oxygen (SpO2 ≤90%); HFNO as bridge to other therapies. • Hot flashes: Fezolinetant (nonhormonal NK3 antagonist); gabapentin 900 mg/day; progesterone analogues; oxybutynin.
- Mucositis and Nasal Vestibulitis Management: • Oral mucositis: Cryotherapy for fluorouracil; viscous lidocaine 2% for pain; topical steroids for ulcers. • Nasal vestibulitis: Saline/rose geranium in sesame oil nasal sprays (compounded).
- Gastrointestinal Management: • Constipation: Loperamide up to 24 mg/day; octreotide 300 mg/day for refractory cases.
- CIPN Management: • Action: Discontinue/attenuate neurotoxic chemotherapy (per ASCO guidelines for significant CIPN). • Emerging: Cryotherapy/compression therapy (under study).
Pain Management¶
• Nociceptive pain: Acetaminophen → NSAIDs → opioids (with constipation prevention). • Visceral pain: NSAIDs/gabapentin/pregabalin + opioids; octreotide for malignant bowel obstruction. • Neuropathic pain: Duloxetine (moderately effective); gabapentin/pregabalin; opioids (equally effective as gabapentin/nortriptyline). Trials require 3–4 weeks to assess efficacy. • Incident pain: Low-dose gabapentin (100–200 mg TID) + opioids.
Nausea and Vomiting Management¶
• Chemotherapy-related: Dexamethasone, 5-HT3 antagonists, NK1 antagonists, olanzapine (most effective). Four-drug cocktail: dexamethasone + 5-HT3 antagonist + NK1 antagonist + olanzapine. • Non-chemotherapy: Olanzapine 5 mg/day.
Anorexia, Cachexia, and Constipation Management¶
• Anorexia/cachexia: Olanzapine 2.5 mg nightly (60% weight gain vs 9% placebo in RCT). • Constipation: Assess bowel habits; >3 days since last BM = likely constipation. Loperamide up to 24 mg/day; octreotide for refractory cases.
Dyspnea and Hot Flashes Management¶
• Dyspnea: Supplemental oxygen (SpO2 ≤90%); HFNO as bridge to other therapies. • Hot flashes: Fezolinetant (nonhormonal NK3 antagonist); gabapentin 900 mg/day; progesterone analogues; oxybutynin.
Mucositis and Nasal Vestibulitis Management¶
• Oral mucositis: Cryotherapy for fluorouracil; viscous lidocaine 2% for pain; topical steroids for ulcers. • Nasal vestibulitis: Saline/rose geranium in sesame oil nasal sprays (compounded).
8. PROGNOSIS & COMPLICATIONS¶
Prognostic factors and complications include:
• Fatigue: Poor prognosis if unresponsive to interventions. • CIPN: Persistent neuropathy may require long-term management. • Mucositis: Risk of infection/sepsis with severe GI mucositis. • Nasal vestibulitis: Potential for secondary infection. • Olanzapine use: Weight gain, sedation, metabolic syndrome risk. • High-dose steroids: Hyperglycemia, immunosuppression, osteoporosis risk.
9. SPECIAL CONSIDERATIONS¶
Special considerations:
• PROs: Improve survival and quality of life; ESAS–FS is free, multidimensional, and available in multiple languages. • Olanzapine for anorexia: Only agent with proven benefit without serious harm. • Duloxetine for CIPN: Only proven medication. • Fezolinetant for hot flashes: Nonhormonal alternative. • HFNO use: Cost barriers to hospice/home care.
10. KEY PEARLS & CLINICAL TRAPS¶
Key pearls and clinical traps:
• Fatigue management: Prioritize structured exercise and correcting reversible causes (anemia/hypothyroidism); consider bupropion. • Pain management: Opioids effective for neuropathic pain; duloxetine is the only proven CIPN treatment. • Nausea/vomiting: Olanzapine is most effective in a four-drug cocktail; 5 mg/day is effective for non-chemotherapy nausea. • Anorexia/cachexia: Olanzapine 2.5 mg nightly improves weight gain; monitor for metabolic side effects. • Hot flashes: Fezolinetant and gabapentin are effective nonhormonal options. • Mucositis: Cryotherapy prevents fluorouracil-induced mucositis; lidocaine 2% provides local pain relief. • CIPN: Discontinue/attenuate neurotoxic chemotherapy for significant CIPN. • Clinical traps: Overlooking depression in fatigue, underestimating CIPN impact, and inappropriate steroid use.
Reference Tables¶
TABLE 74-1 Common Cancer Symptoms and Their Association SYMPTOM Fatigue Pain, all¶
Harrison's 22e, p.507
| SYMPTOM | PREVALENCE | COMMONLY FOUND CAUSES/EXAMPLES |
|---|---|---|
| Fatigue | 70–80% | Chemotherapy Immunotherapy |
| 40–70% overall | ||
| Oral and gastrointestinal toxicity |
Dependent on agents used; estimates from 30 to 40% | Standard chemotherapy such as doxorubicin Molecularly targeted agents such as palbociclib, infigratinib, everolimus, lenvatinib Radiation therapy |
| Dependent on emetogenic potential of drugs administered; 10–90% |
||
| Nausea not due to chemotherapy |
Limited information on incidence but common | Due to small-bowel obstruction, opioids |
| 20–80% due to cancer | ||
| Dyspnea | 10–80% during a lifetime, more common near end of life | Most common in lung cancer patients or those with effusions, multiple pulmonary metastases |
| Two-thirds of breast cancer and three-quarters of prostate cancer patients with androgen deprivation |
||
| Nasal vestibulitis | Up to 75% of patients | Those receiving taxanes, bevacizumab, etc. |
TABLE 74-2 Types of Commonly Encountered Cancer Pain¶
Harrison's 22e, p.508
| TYPE OF PAIN | CAUSE | CHARACTERISTICS | EXAMPLES |
|---|---|---|---|
| Nociceptive | Pressure on nerves | Deep, dull, aching, constant and worsening with time |
Pancreatic cancer pain, deep boring, and epigastric |
| Distention of a hollow viscus | Cramping, bloating pain, intermittent | ||
| Neuropathic | Direct damage to the nerves from cancer, treatment, or both |
Local pain, sharp shooting, burning, stabbing, often with allodynia (painful sensation with normal touch) or hyperalgesia |
|
| Chemotherapy-induced neuropathic pain; direct damage to the longest nerves with damaged receptors and even loss of nerve fiber density |
Numbness, tingling, pain, which may be mixed together; longest nerves affected most, giving a stocking-glove neuropathy |
||
| Incident or movement pain |
Pathologic fractures, bone damage from cancer, residual damage left after cancer |
Minimal pain at rest, but excruciating pain with movement “bone on bone” |
Very difficult to control |