Colorectal cancer investigational agents

TABLE 1 27—1 2. Investigational Agents for the Treatment of Colorectal Cancer... 

Chemotherapy. Comparisons of fluorouracil-based regimens alone and in combination with other agents, including trimetrex-ate, raltitrexed, methotrexate, interferon-a, and N-(phosphonacetyl)-L-asparte (PALA), have also been investigated in previously untreated patients with metastatic colorectal cancer. Trimetrexate, raltitrexed, and methotrexate improve response rates and have small effects on progression-free intervals with minimal or no effect on overall survival. The addition of interferon-a or PALA to fluorouracil plus leucovorin increases toxicities and does not improve overall efficacy. 

Given the encouraging safety and therapeutic benefit of °Y in both primary and metastatic liver disease, there is an opportunity to explore its application in combination with other available therapies. Studies to assess the potential synergistic therapeutic benefit of °Y and known radio-sensitizers in both metastatic breast and colorectal cancer are warranted. Combination capecitabine and Y present a low toxicity option for breast cancer patients. The potential to improve hepatic tumor response via the synergistic action of selective uptake of 5-FU in the presence of radiation warrants further investigation. °Y in combination with 5-FU, FUDR and capecitabine in colorectal metastases to the liver require further study. Given the potential for super irradiation of liver parenchyma in the presence of these agents, carefully controlled Phase I dose escalation studies are required. 

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