Side Effects of Treatments for Neuroendocrine Tumors (NETs)
The most common side effects of NET treatments include gastrointestinal symptoms (diarrhea, abdominal pain, nausea), cholelithiasis, hyperglycemia/hypoglycemia, and fatigue, with specific side effect profiles varying by treatment modality. 1, 2
Somatostatin Analogs (SSAs) - First-Line Therapy
Somatostatin analogs (octreotide, lanreotide) are commonly used for both functional and non-functional NETs. Their side effects include:
- Gastrointestinal effects: Diarrhea, abdominal pain, nausea, flatulence, vomiting (occurring in 20-40% of patients) 2
- Gallbladder abnormalities: Up to 62% of patients develop new biliary abnormalities including gallstones (24%), sludge, and biliary dilatation 2
- Glucose metabolism disturbances: Hyperglycemia (27%) and hypoglycemia (4%) 2
- Cardiac effects: Sinus bradycardia (19%), conduction abnormalities (9%), arrhythmias (3%) 2
- Injection site reactions: Pain, erythema, swelling
- Thyroid function: Hypothyroidism (rare) 2
Important caution: SSAs should be used with extreme caution in patients with insulinoma as they can worsen hypoglycemia by suppressing counterregulatory hormones 1
Targeted Therapies
Everolimus (mTOR inhibitor)
- Stomatitis/mucositis (common)
- Hyperglycemia (frequent and potentially severe)
- Fatigue (common)
- Diarrhea (common)
- Pneumonitis (rare but serious) 1
- Anemia (common) 1
- Rash (common) 1
Sunitinib (Tyrosine Kinase Inhibitor)
- Fatigue (very common)
- Hypertension (common)
- Hand-foot syndrome (palmar-plantar erythrodysesthesia)
- Diarrhea (common)
- Congestive heart failure (rare but serious) 1
- Myelosuppression (common)
Cytotoxic Chemotherapy
Side effects vary by regimen but commonly include:
- Myelosuppression: Neutropenia, thrombocytopenia, anemia
- Nausea and vomiting
- Alopecia
- Fatigue
- Mucositis
Streptozocin-based regimens:
- Nephrotoxicity (dose-limiting)
- Nausea/vomiting (severe)
- Glucose abnormalities (due to pancreatic β-cell toxicity)
Temozolomide-based regimens:
- Myelosuppression (dose-limiting)
- Nausea
- Fatigue
Peptide Receptor Radionuclide Therapy (PRRT)
PRRT using radiolabeled somatostatin analogs (90Y-DOTATOC or 177Lu-DOTATATE) has specific side effects:
- Hematological toxicity: Thrombocytopenia, leukopenia, anemia 1
- Nephrotoxicity: More common with 90Y-labeled compounds than with 177Lu-labeled compounds 1
- Hepatotoxicity: Rare but can occur
- Nausea and vomiting: Usually mild and transient
- Hormone crisis: Rare but potentially life-threatening release of hormones during treatment
- Long-term risks: Secondary myelodysplastic syndrome or leukemia (rare, <2% of cases) 1
Hepatic-Directed Therapies
For patients with liver-predominant metastatic disease:
Embolization/Chemoembolization/Radioembolization:
- Post-embolization syndrome: Fever, pain, nausea, vomiting (very common)
- Hepatic abscess or biloma (uncommon)
- Hepatic dysfunction (transient elevation of liver enzymes is common)
- Renal dysfunction (from contrast exposure)
Radiofrequency Ablation/Cryoablation:
- Pain
- Bleeding
- Infection
- Damage to adjacent structures
Monitoring Recommendations
- Regular liver function tests - especially with hepatic-directed therapies and some systemic treatments
- Complete blood counts - particularly with PRRT and cytotoxic chemotherapy
- Blood glucose monitoring - especially with SSAs and everolimus
- Renal function tests - particularly important with PRRT and streptozocin
- Thyroid function tests - periodically with SSA therapy
- Cardiac monitoring - especially in patients receiving SSAs with pre-existing cardiac disease
- Gallbladder ultrasound - periodically in patients on long-term SSA therapy
Management of Common Side Effects
- Diarrhea: Loperamide, dietary modifications, dose adjustments
- Hyperglycemia: Blood glucose monitoring, antidiabetic medications as needed
- Stomatitis: Oral hygiene, topical treatments, dose adjustments
- Fatigue: Activity pacing, addressing anemia if present
- Nausea/vomiting: Antiemetics, hydration
Understanding the side effect profile of each treatment is essential for appropriate patient selection, monitoring, and management. The choice of therapy should consider both efficacy and tolerability, with close monitoring for adverse effects to allow for early intervention.