Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases

ABSTRACT

Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10–20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential.

Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options.

Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no ‘single best approach’, making further trials necessary to provide more evidence.

KEYWORDS:

• Colon cancer
• rectal cancer
• liver metastases
• chemotherapy
• survival

Article highlights

• Surgical resection remains the best treatment approach in patients with colorectal cancer with liver metastases (CRC-LM). However, upfront surgery is only possible in about 10–20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential.

• Management of patients with CRC-LM requires a multidisciplinary approach consisting of a team of specialists in oncology, surgery, radiology, and radiotherapy to plan the treatment on a case-by-case basis.

• In resectable disease, most groups recommend the use of perioperative chemotherapy use. The ideal perioperative systemic chemotherapy regimen in this setting still debatable. Most guidelines recommend the use of a fluorouracil-based chemotherapy combined with oxaliplatin. Not enough evidence is present to support the addition of targeted therapy in this setting making it not recommended in most guidelines.

• In CRC-LM, the main line of treatment is chemotherapy which aims at converting the liver metastases into resectable (conversion therapy), or at least improving overall survival and delaying the progression of the disease.

• Conversion therapy usually includes the use of combinations of systemic chemotherapeutic agents with or without the addition of targeted therapy agents.

• The drawback of using systemic chemotherapy combinations in CRC-LM is the development of adverse events and toxicities which can negatively impact quality of life. These complications can, in many cases, limit the recommendation of certain chemotherapeutic regimens in certain settings.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.