Chemotherapy plays a critical role in the treatment of neuroendocrine tumours (NETs), particularly for high-grade or aggressive forms of the disease. Chemotherapy is typically used in about 20-30% of neuroendocrine cancer cases, particularly in high-grade neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs).
While NETs are generally less responsive to chemotherapy compared to other cancers, it remains an important option for specific subtypes, especially those that are fast-growing or have metastasised.
Chemotherapy can be used either as a standalone treatment or in combination with other therapies, such as surgery, somatostatin analogues (SSAs), or peptide receptor radionuclide therapy (PRRT).
Neuroendocrine Cancer Australia (NECA), is dedicated to supporting individuals diagnosed with NETs, and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.
The aim of chemotherapy is to reduce tumour size, control symptoms, and improve survival outcomes. However, it is used in different ways depending on the patient and the progression of disease:
Chemotherapy is primarily used for treating neuroendocrine carcinomas (NECs), which are high-grade, poorly differentiated tumours with a more aggressive clinical course. For well-differentiated high grade (Grade 3) NETs and intermediate (Grade 2) NETs, chemotherapy is typically considered when the disease becomes advanced, metastatic, or resistant to other treatments.
While not all NETs respond well to chemotherapy, certain subtypes, particularly high-grade and fast-growing tumours, tend to be more responsive.
In treating NETs, chemotherapy can be administered as a standalone therapy, particularly for patients with high-grade or metastatic disease.
It may also be combined with:
Chemotherapy might seem like a catch-all term. However, there are actually distinct types that can be deployed to treat certain types of tumours in different stages around different parts of the body.
Cisplatin and etoposide are commonly used chemotherapeutic agents for treating high-grade neuroendocrine carcinomas (NECs). This combination is particularly effective for rapidly growing, poorly differentiated tumours, such as small-cell lung cancer and aggressive gastrointestinal NETs.
How it works:
Cisplatin works by damaging the DNA in cancer cells, preventing them from dividing, while etoposide inhibits enzymes that are essential for DNA replication.
Streptozocin, often used in combination with 5-fluorouracil (5-FU) or doxorubicin, is a preferred chemotherapy option for pancreatic neuroendocrine tumours (pNETs). This regimen is particularly useful for well-differentiated pNETs, where other therapies may not be as effective.
How it works:
Streptozocin targets the DNA of cancer cells, inducing cell death, and has been shown to significantly reduce tumour size in some patients.
Capecitabine and temozolomide, commonly referred to as the CAPTEM regimen, is a newer chemotherapy combination used for treating low – to intermediate-grade NETs. CAPTEM has shown promising results in patients with pancreatic NETs and other low-grade tumours. CAPTEM can be used in combination with PRRT.
How it works:
Capecitabine, an oral prodrug of 5-FU, interferes with DNA synthesis in cancer cells, while temozolomide is an alkylating agent that induces cell death by damaging the DNA.
Doxorubicin, 5-fluorouracil (5-FU), and other chemotherapeutic agents may be used in specific NET cases, often in combination with other drugs. While less commonly used as frontline therapies, these agents can be effective in treating NETs that are resistant to standard treatments or in patients who cannot tolerate other regimens.
As mentioned previously, different types of chemo may be used in different scenarios. Let’s take a look at some of the most common ones.
Chemotherapy is most frequently indicated for high-grade or aggressive NETs, where rapid tumour growth and metastasis are common. In these cases, chemotherapy is essential for controlling tumour proliferation and improving survival.
Neuroendocrine carcinomas (NECs) are poorly differentiated, fast-growing tumours that require immediate and intensive treatment, with chemotherapy often being the first line treatment option. Given the aggressive nature of NECs, chemotherapy aims to stabilise the disease, manage tumour progression, lessen symptoms, and improve both survival outcomes and the patient’s quality of life.
For patients with metastatic NETs, chemotherapy can help manage symptoms, slow the progression of the disease, and improve quality of life. It is particularly useful when metastases are present in multiple organs or when other treatments are no longer effective.
In some cases, chemotherapy is used as a neoadjuvant therapy to shrink the tumour before surgery, making it easier to remove. Adjuvant chemotherapy may also be used after surgery to destroy any remaining cancer cells and reduce the risk of recurrence.
In late-stage NETs, where curative treatment is no longer possible, chemotherapy may be used palliatively to manage symptoms, reduce tumour burden, and improve the patient’s quality of life.
Chemotherapy works by targeting rapidly dividing cancer cells. In the case of NETs, chemotherapeutic agents interfere with the cells’ ability to replicate DNA or undergo mitosis, leading to cell death.
By disrupting the growth cycle of cancer cells, chemotherapy can slow tumour proliferation and shrink existing tumours. This is particularly important in aggressive or high-grade NETs, where rapid growth and spread can complicate treatment.
The effectiveness of chemotherapy in NETs depends on the tumour’s growth rate, as faster-growing tumours are generally more sensitive to these drugs.
Response rates based on tumour type and grade
The effectiveness of chemotherapy also depends on the tumour’s type and grade.
Long-term outcomes and survival rates
Long-term outcomes for patients receiving chemotherapy vary based on tumour type, grade, and the extent of the disease.
While chemotherapy can improve survival in some patients, particularly those with high-grade NETs, it may not provide long-term control in cases of low-grade NETs.
However, combining chemotherapy with other treatments may enhance overall survival and quality of life.
Like all cancer treatments, chemotherapy can cause side effects. Understanding and managing these are key to providing better quality of life for patients.
Common side effects include:
Managing the side effects of chemotherapy is an important aspect of patient care. Anti-nausea medications, growth factors to stimulate bone marrow, and other supportive treatments can help mitigate the toxic effects of chemotherapy and improve patient comfort.
While chemotherapy can extend survival, its side effects can also impact a patient’s quality of life. Balancing the benefits of tumour control with the side effects of treatment is essential in developing an appropriate care plan for NET patients.
As mentioned prior, chemo can be combined with other treatments to form better outcomes for patients.
In some cases, chemotherapy is combined with SSAs, especially in patients with metastatic or hormone-secreting NETs. SSAs help control symptoms and tumour growth, while chemotherapy targets rapidly dividing cells, providing a dual approach to treatment.
Chemotherapy may also be used in conjunction with PRRT, particularly in patients with high tumour burdens or aggressive disease. PRRT delivers targeted radiation to NET cells, while chemotherapy works systemically, attacking tumour cells throughout the body.
Chemotherapy is often used before or after surgery to enhance the effectiveness of surgical resection. In cases where surgery is not curative, chemotherapy may help control residual disease or prevent recurrence.
A key theme emerges throughout chemotherapy as a treatment – chemotherapy is not a one-size-fits-all approach. There are a range of ways that chemo can be tailored to the patient.
The role of biomarkers in selecting chemotherapy agents is becoming increasingly important. By identifying specific genetic or molecular characteristics of the tumour, physicians can tailor chemotherapy regimens to target the cancer more effectively, improving patient outcomes.
Personalised treatment approaches take into account not only the tumour’s genetic profile but also the patient’s overall health, age, and response to previous treatments. This individualised approach helps optimise chemotherapy regimens and minimise side effects.
Research is ongoing to develop new chemotherapeutic agents that are more effective and have fewer side effects for NET patients. These new agents may target specific molecular pathways involved in tumour growth and provide additional options for patients who have not responded to traditional chemotherapy.
Numerous clinical trials are exploring novel combinations of chemotherapy with other therapies, such as targeted drugs, immunotherapies, and radiation. These trials aim to improve treatment outcomes and expand the options available to NET patients.
As our understanding of NET biology continues to evolve, there is potential for more personalised chemotherapy treatments. By targeting the specific genetic and molecular characteristics of a patient’s tumour, future chemotherapy regimens may be more effective and less toxic, offering new hope for those with NETs.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.
