CHEMOTHERAPY AND ADVANCED THERAPIES IN COLORECTAL CANCER TREATMENT

With the aim of providing Vietnamese patients with the most advanced treatments, the doctors at Hanoi French Hospital continuously collaborate with leading global experts, notably Professor Thierry André—one of the world’s foremost specialists in medical oncology, particularly in gastrointestinal cancers.

Professor Thierry André is an oncology professor at Sorbonne University (Paris, France), Head of the Oncology Department at Saint-Antoine Hospital (Paris, France), and Vice President of the GERCOR Multidisciplinary Cancer Research Group.

He has authored numerous major studies on cancer treatment, most notably the FOLFOX regimen and immunotherapy protocols, which represent the latest advancements in first-line treatment for metastatic colorectal cancer.

Below, Professor Thierry André provides an in-depth analysis of the most advanced therapies for colorectal cancer treatment.

Chemotherapy – the primary treatment to destroy colorectal cancer cells

For localized disease, the tumor in the colon or rectum is surgically removed. In some cases, adjuvant therapy—chemotherapy after surgery—is recommended to reduce the risk of recurrence. For stage III patients, where lymph node metastasis is found in the surgical specimen, adjuvant chemotherapy is essential, as it offers the highest therapeutic benefit.

Without adjuvant chemotherapy, the recurrence risk (metastases or, less commonly, local recurrence) after surgery is about 40%. The risk is lower if the tumor is small and only 1–3 lymph nodes are affected but higher if the tumor is large and more than 3 lymph nodes are involved. Adjuvant chemotherapy improves the cure rate from 50–60% after surgery alone to approximately 75–80% when combining surgery and chemotherapy.

The standard adjuvant chemotherapy regimens include: 5-fluorouracil (5-FU) or capecitabine ± oxaliplatin. The two most effective regimens are FOLFOX (folinic acid, 5-FU, oxaliplatin) and CAPEOX (capecitabine, oxaliplatin). These regimens reduce the risk of recurrence, with a treatment duration of 3 to 6 months, depending on the case.

For advanced disease with metastases that cannot be surgically removed, chemotherapy may be the only treatment option and is often combined with targeted therapy.

The standard regimens include: 5-FU + oxaliplatin (FOLFOX) or 5-FU + irinotecan (FOLFIRI), administered every two weeks. An alternative is capecitabine + oxaliplatin, given every three weeks. In some cases, a stronger regimen (FOLFIRINOX)—which includes all three drugs (oxaliplatin, 5-FU, irinotecan)—may be used.

Targeted therapy – personalized treatment based on molecular testing

Advancements in molecular biology have identified cancer-driving mechanisms, leading to the development of targeted therapies. These drugs act directly on the biological pathways of cancer cells, slowing or stopping their growth.

For metastatic colorectal cancer, additional tests on the initial biopsy sample help determine the targeted therapy to combine with chemotherapy. Next-Generation Sequencing (NGS) technology enables simultaneous analysis of multiple genes, detecting tumor DNA mutations such as RAS and BRAF to establish a molecular profile and identify the optimal treatment.

• If there is no RAS gene mutation, patients may receive cetuximab or panitumumab (EGFR inhibitors) combined with chemotherapy, particularly if the tumor is located in the left colon or rectum.
• If there is an RAS mutation or the tumor is in the right colon, angiogenesis inhibitors such as bevacizumab or aflibercept are used with chemotherapy.
• For metastatic cancer with a BRAF mutation, the combination of encorafenib (a kinase inhibitor) and cetuximab (an EGFR inhibitor) is recommended if first-line chemotherapy fails.

Immunotherapy – activating the immune system to fight cancer

Only about 5% of metastatic colorectal cancer patients benefit from immunotherapy. These are primarily patients with microsatellite instability (MSI) or deficient mismatch repair (dMMR).

Thus, all colorectal cancer patients should undergo MSI/dMMR testing on their biopsy or surgical specimen using molecular biology or immunohistochemistry techniques.

If a patient has MSI/dMMR, they can be treated with pembrolizumab or nivolumab ± ipilimumab, which have shown high efficacy without chemotherapy, according to recent studies.

New drugs and treatment prospects

New drugs such as trifluridine-tipiracil, regorafenib, and fruquitinib have been developed to prolong survival for patients when previous treatments are no longer effective.

With ongoing research in molecular biology and drug resistance mechanisms, more new treatment targets are being identified, opening up promising opportunities for colorectal cancer patients.

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Hanoi French Hospital (HFH)

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