Metastatic CRC

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based chemotherapy regimens with the addition of irinotecan (CPT-11) or oxaliplatin. It still remains a challenge for oncologists to evaluate the reasons for a wide variation in response and toxicity among patients undergoing systemic 5-FU based chemotherapy. Pharmacogenomics... 

Until the year 2000, the only systemic therapy for metastatic CRC was a bolus or infusional 5-FU regimen, mostly in combination with leucovorin (5-FU/LV), achieving a median survival of 12 month (20). However, over the last 6 years many new agents have been developed and approved by the Federal Drug and Food Administration (FDA) for the treatment of mCRC (7). A summary of the current guidelines for treating colorectal cancer is shown in Table 1. 

ADCC. Cetuximab is approved for treatment of metastatic colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN). Interestingly, an adverse event, acneiform rash seems to correlate with a better response to cetuximab, while there is no such correlation with expression levels of EGFR assessed by immunohistochemistry. Further side effects are rare infusion reactions and hypomagnesia. Two other anti-EGFR antibodies approved for clinical use are the fully human antibody panitumumab (Vectibix)... 

Matrix metalloproteinases-2 and -9 facilitated tumour invasion via basement membrane degradation. Metastatic colorectal cancer cells (CRC line W620) induced matrix metalloproteinase release by human THP-1 monocytes (Swallow et al. 1996). 

Ischaemic hver may be toxic to weakly metastatic human colorectal cancer (CRC) cells on reoxygenation (Jessup et al. 1999). This toxicity involves reactive oxygen and nitrogen species. 

Saltz LB, Locker PK, PirottaN, et al (2000) Weekly irinotecan (CPT-11) leucovorin (LV), and fluorouracil (FU) is superior to daily X5LV/FU in patients (pts) with previously untreated metastatic colorectal cancer (CRC). Proc Am Soc Clin Oncol 18 898 Abstract... 

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