New and current second-line treatments

This review discusses current second-line treatment options for metastatic colorectal cancer, as well as new advances in colorectal cancer therapy.

Colorectal cancer (CRC) is the third most common cancer in the world, and up to 40% of CRC patients will experience metastasis, or spread, of the disease. Advances in initial (first-line) treatments have increased survival rates, but recurrence of the cancer, or progression of the disease despite treatments, also lead to an increase in the number of patients who require additional (second-line) treatments.

In the past, the choice of second-line treatments was limited, and based on the type of first-line treatment received. Recent advances, however, have created several new options for the second-line treatment of metastatic disease. The current review evaluated the available second-line treatments for metastatic colorectal cancer (mCRC), as well as recent advances in colorectal cancer therapy.

Currently, standard second-line treatments include chemotherapy with irinotecan alone, or chemotherapy regimens such as FOLFIRI or FOLFOX, which include a combination of several chemotherapy drugs (such as 5-fluorouracil, leucovorin, and oxaliplatin). These combinations have been shown to be most effective as second-line treatment of metastatic cancer.

The inclusion of molecular-targeted drugs such as bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix) have been shown to improve both overall survival and quality of life in many mCRC patients. Molecular-targeted drugs inhibit certain biological actions necessary for cancer growth and spread. For example, bevacizumab inhibits the formation of new blood vessels necessary for tumor growth, and cetuximab prevents cancer cells from responding to growth hormones circulating in the body.

Aflibercept (Zaltrap) is a recently developed drug that blocks new blood vessel formation in a similar manner to bevacizumab. Aflibercept combined with the FOLFIRI chemotherapy regimen has been shown to increase overall survival by up to 20% compared to FOLFIRI chemotherapy alone. However, aflibercept has also been shown to cause higher rates of adverse side effects such as diarrhea, weakness, and infections. 

Although first-line treatments are generally not continued as second-line therapy, recent studies have shown that continuing bevacizumab in combination with a different chemotherapy agent can be beneficial. Bevacizumab continuation was shown in one study to increase the time before disease progression by 1.6 months, and overall survival by 1.4 months. Continuation of bevacizumab was not associated with increased side effects.

This review concluded that multiple options for second-line treatment of metastatic colorectal cancer exist. Disease characteristics and the possibility of side effects need to be taken into consideration when determining the best course of treatment.

Consult with your physician regarding the risks and benefits of all treatment options for metastatic colorectal cancer.