What conditions can peptide therapy be used for?

Peptide Therapy Applications in Medical Conditions

Peptide therapy is primarily indicated for neuroendocrine tumors (NETs), particularly for symptom control and as an antiproliferative treatment, with somatostatin analogues being the most established peptide therapeutics in clinical practice. 1

Neuroendocrine Tumors (NETs)

Symptom Control

• Somatostatin analogues (octreotide, lanreotide) are first-line peptide therapies for controlling symptoms in functional NETs, particularly carcinoid syndrome with flushing and diarrhea, with control rates of 40-90% 1
• Standard dosing includes octreotide LAR 20-30 mg intramuscularly every 4 weeks or lanreotide 120 mg deep subcutaneously every 4 weeks 1, 2
• Short-acting octreotide (150-250 mcg subcutaneously three times daily) can be added for breakthrough symptoms or rapid relief 1
• Telotristat ethyl (250 mg three times daily), a tryptophan hydroxylase inhibitor peptide, is approved for diarrhea associated with carcinoid syndrome when insufficiently controlled with somatostatin analogues 1

Antiproliferative Treatment

• Octreotide LAR has demonstrated antiproliferative effects in midgut NETs, extending time to tumor progression from 6.0 to 14.3 months compared to placebo (PROMID study) 1, 2
• Lanreotide has shown improvement in progression-free survival in pancreatic and intestinal NETs with Ki-67 up to 10% (CLARINET study) 1, 2
• For progressive disease after somatostatin analogue therapy, peptide receptor radionuclide therapy (PRRT) with radiolabeled peptides is recommended 1, 2

Peptide Receptor Radionuclide Therapy (PRRT)

• PRRT using radiolabeled peptides (177Lu-DOTATATE, 90Y-DOTATOC) has shown significant efficacy in NETs with high somatostatin receptor expression 1
• The NETTER-1 trial demonstrated significant improvement in progression-free survival with 177Lu-DOTATATE compared to high-dose octreotide in midgut NETs 1, 2
• Objective response rates of 18% have been reported with 177Lu-DOTATATE versus 3% with high-dose octreotide 1
• PRRT can be considered for symptom control in patients with refractory functional NETs 1

Bronchial and Thymic Neuroendocrine Tumors

• Somatostatin analogues and interferon-alpha are treatment options for low-proliferating bronchial and thymic carcinoids with severe clinical symptoms 1
• Treatment with these peptides has resulted in partial response in 5-10% of cases, stable disease in 30-50%, and symptomatic improvement in 40-60% 1
• PRRT is an option for patients with tumors showing high somatostatin receptor expression, with tumor shrinkage reported in >50% of treated patients 1

Growth Hormone-Related Conditions

• Growth hormone-releasing peptides (GHRPs) have been investigated for growth hormone deficiency in children 3, 4
• Intranasal GHRP-2 administration has shown modest but significant increases in growth velocity in children with short stature 4
• Growth hormone-releasing hormone (GHRH) has clinical utility in establishing the etiology of GH deficiency and potentially treating GH-deficient children 5

Important Clinical Considerations

Patient Selection

• Somatostatin receptor expression is crucial for efficacy of somatostatin analogues and PRRT, with 70-95% of NETs expressing these receptors 1
• Only about 50% of insulinomas express somatostatin receptors, making peptide therapy less effective for this tumor type 1
• Poorly differentiated NETs and somatostatinomas have lower somatostatin receptor expression and may respond less well to peptide therapies 1

Potential Adverse Effects

• Somatostatin analogues may predispose patients to gallstones; gallbladder removal is often performed during liver surgery for NETs 1
• PRRT can cause temporary myelosuppression, radiation nephritis, and nausea/vomiting during treatment 1
• Acute worsening of hormonal symptoms may occur during or after PRRT (e.g., worsening hypoglycemia in insulinoma or diarrhea in carcinoid syndrome) 1

Emerging Applications

• Peptide therapeutics are being increasingly explored due to their high selectivity, efficacy, and favorable safety profile 6
• Novel approaches include multifunctional peptides, cell-penetrating peptides, and peptide drug conjugates 6
• Peptide therapy is being investigated for aging, catabolic states, and dilated cardiomyopathy 7

While peptide therapy has shown the most established clinical benefit in neuroendocrine tumors, ongoing research continues to expand its potential applications to other conditions, with the development of novel peptides and delivery systems enhancing therapeutic possibilities.