The Effect of Aggressive Chemotherapy in Advanced Colon Cancer

According to research published by the American Society of Clinical Oncology, bevacizumab with four-drug chemotherapy significantly increased survival in advanced (metastatic) colon cancer patients younger than 75.

Advanced (metastatic) colon cancer develops in two forms. The first is widely spread cancer that cannot be treated surgically. In the second, cancer has spread to a single or limited area. If spread is to one organ, cancer is confined to that organ, allowing regional treatment such as surgery. However, most advanced colon cancers are widely spread and cannot be cured surgically. Chemotherapy, radiotherapy, and targeted treatments (bevacizumab, cetuximab, panitimumab) then produce favorable results. Combining chemotherapy regimens with targeted smart drugs aims to increase treatment effectiveness and prolong survival.

Chemotherapy drugs such as irinotecan, oxaliplatin, leucovorin, fluorouracil, and capecitabine stop tumor cell development through different mechanisms. Some kill tumor cells while others prevent multiplication. Bevacizumab, used as targeted treatment in colon cancer, both prevents tumor cell growth and spread and facilitates their destruction by increasing chemotherapy effectiveness. Combined treatments adding smart drugs to chemotherapy ultimately aim to destroy more tumor cells.

For this purpose, in routine practice our stage-four colon cancer patients are treated with irinotecan or oxaliplatin as the main drug, two supporting drugs (5FU, leucovorin), and an additional smart drug. These regimens are known by abbreviations derived from their components: FOLFOX (oxaliplatin, 5FU, leucovorin) and FOLFIRI (irinotecan, 5FU, leucovorin). Discovery of smart drugs over the years and their addition to these combinations markedly increased regimen effectiveness. One treatment is selected first for a stage-four patient and continued while effective. When imaging shows progression, in other words no response to treatment, the other regimen is used, with one of the smart drugs described above added according to patient and tumor characteristics to improve success.

An important study presented this year at the ASCO GI congress in America compared the four-drug chemotherapy regimen described above (FOLFOXIRI: oxaliplatin, irinotecan, 5FU, leucovorin) plus bevacizumab with our routine three-drug regimen plus bevacizumab in advanced colon cancer. Over approximately 3 years, patients younger than 75 with advanced colon cancer received either bevacizumab with four-drug chemotherapy (FOLFOXIRI) or bevacizumab with three-drug chemotherapy (FOLFIRI). The findings indicated that toxicity associated with increasing drug numbers in more intensive combinations was manageable, but treatment was unsuitable for patients older than 75 or those aged 70-75 in poor general health.

However, the study showed that bevacizumab with four-drug chemotherapy (FOLFOXIRI), in advanced colon cancer patients younger than 75 in good general health, doubled overall survival at 5 years. This indicates that it is a valuable option for advanced colon cancer patients able to tolerate it.