Chemotherapy colorectal cancer

The clinical trial that resulted in FDA approval of bevacizumab (February 2004) was a randomized, double-blind, phase III study in which bevacizumab was administered in combination with bolus-IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previously untreated metastatic colorectal cancer [3]. Median survival was increased from 15.6 months in the bolus-IFL + placebo arm to 20.3 months in the bolus-IFL + bevacizumab arm. 

Fluorouracil-based chemotherapy is the standard of care for the adjuvant treatment of colorectal cancer either as a single agent or, more commonly, in combination with other agents. 5-Fluorouracil (5-FU) alone results in a small improvement in survival that can vary based on the method of 5-FU administration. Studies suggest that protracted or continuous intravenous (IV) 5-FU infusion treatment schedules are more effective than bolus therapy.20... 

CA 125 is a mucin-like glycoprotein antigenic determinant expressed on the surface of coelomic epithelium and human ovarian carcinoma cells however, it does not appear to be specific for ovarian cancer because elevated levels have been reported in breast and colorectal cancers. Studies have shown increased CA 125 levels in patients with ovarian cancer, whereas decreased CA 125 levels in chemotherapy are associated with improved possibility for survival. Some studies have shown failure of CA 125 levels to return to normal after chemotherapy, indicating... 

Chemotherapy is the primary treatment modality for metastatic colorectal cancer (MCRC). Treatment options are generally similar for metastatic cancer of the colon and rectum. 

Chemotherapy Regimens for the Adjuvant Treatment of Colorectal Cancer... 

Human cancers vary widely in their ability to produce metastasis. At present, there are no reliable methods to predict metastatic potential. For optimum patient management, however, knowledge of the aggressiveness of a tumor is desirable when deciding which patients should receive adjuvant chemotherapy. This type of information is particularly important for axillary node-negative breast cancer and Dukes B colorectal cancer. 

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths in the United States. (77). The incidence is approx. 40 per 100,000 in men and 25-30 per 100,000 in women (78). For those with stage 111 disease with presumed micrometastatic disease, adjuvant chemotherapy is used, typically 5-fluorouracil (5-FU) and leucovorin for 6-8 mo, with a 30% reduction in disease recurrence and 22-32% reduction in mortality (79,80). 

Elsaleh H, Joseph D, Grieu F, et al. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 2000 355(9217) 1745-1750. 

Adjuvant chemotherapy involves the use of antineoplastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosarcoma in adults. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

The clinical implications of both amplification and loss in tumors have been studied. In a study of 29 Dukes C colorectal cancer patients, those with tumors that had two or more chromosomal regions of gain or loss had significantly better prognosis than patients with less (p = 0.02) (21). Loss of chromosome 5q and lack of 8q amplification in serous ovarian cancer n = 96) is associated with improved prognosis (5-year survival of 75% versus 0% with no loss on 5q and amplification on 8q p = 0.0007) (22). In childhood ALL the amplification of specific chromosomes, chromosome regions, and genes has been associated with chemotherapy resistance and clinical outcome (23,24). 

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... 

Ichikawa W, Uetake H, Shirota Y et al. Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Clin Cancer Res 2003 9 786-791. 

Cohen V, Panet-Raymond V, SabbaghianN et al. Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. Clin Cancer Res 2003 9 1611-1615. 

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