Chemotherapy in Poorly Differentiated pNETs

Cytotoxic chemotherapy remains the mainstay of treatment for individuals with advanced poorly differentiated pancreatic neuroendocrine tumors (pNETs), states Pamela L. Kunz, MD. Typically a platinum-based regimen is used, such as platinum etoposide.

Ongoing research is investigating the benefit of temozolomide versus temozolomide in combination with capecitabine in metastatic pNETs. Individuals who may benefit the most from this therapy are those who require tumor shrinkage, such as patients with bulky disease, rapidly progressive disease, or those who are symptomatic, says Kunz.

In a phase II study, those with pNETs experienced a 45% partial response rate and a 55% stable disease rate with the combination of capecitabine and temozolomide. The median progression-free survival was >18.5 months. In a separate single-institution review, the combination showed a partial response in 47% and a stable disease rate of 27%.

Temozolomide is an alkylating agent, notes Diane Reidy-Lagunes, MD. Its use is associated with the risk of long-term toxicities, such as bone marrow suppression, opportunistic infections, and development of secondary malignancies. The duration of temozolomide therapy does not typically exceed 1 year, due to these risks. However, clinicians have reported continued disease response and tumor shrinkage even while patients were on a treatment holiday. These responses have lasted as long as 1 year, comments Lagunes.