Colon cancer metastatic

Oxaliplatin (Eloxatin ) is similar to other platinum analogs (e.g., cisplatin) in that it binds to the N-7 position of guanine, which results in cross-linking of DNA and double-stranded DNA breaks.26,40 Oxaliplatin differs from cisplatin in that the DNA damage induced by oxaliplatin may not be as easily recognized by DNA repair genes often seen in colorectal cancer. Oxaliplatin, in combination with 5-FU-based regimens, is indicated for the first- and second-line treatment of metastatic colon cancer, as well as the adjuvant treatment of colon cancer. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

T. J. Yeatman, Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential, Oncogene 15 3083 (1997). 

RT can be administered with curative surgical resection to prevent local recurrence of rectal cancer, before surgery to shrink a rectal tumor and make it operable, or in advanced or metastatic disease to alleviate symptoms. Adjuvant RT, however, does not have a definitive role in colon cancer because recurrences are usually extrapelvic. 

UGTIAI has an important role in the metabolism of irinotecan, etoposide, epiru-bicine, and tipifamib. Irinotecan is a camptothecin derivative used in the treatment of metastatic colon cancer. Irinotecan is a prodrug since it is activated to Ethyl-10-hydroxycamptothecin (SN-38) by carboxyl esterase to exert its antitumor activity mediated by the inhibition of topoisomerase I. SN-38 undergoes UGTIAI-catalyzed glucuronide conjugation to form the inactive SN-38 glucuronide (SN-38G). 

The cancer cell lines SW480 and SW620 are two colon cancer cell lines that were obtained from the same patient the SW480 cell line was obtained from the primary tumor, and the SW620 cell line was obtained from a metastatic site. (Adapted from Seeram et al., 2004)... 

Patients with metastatic colon cancer homozygous for the triple tandem repeat (TSER-3R/3R) had significantly higher intratumoral TS gene expression compared with those with double tandem repeats (TSER-2R/2R) within the 5 -UTR region (3,57). 

In 2004, bevacizumab (Avastin) became the first antiangiogenesis drug to receive FDA approval. It is intended for combination use with standard chemotherapy for metastatic colon cancer. Approval for other indications as part of combination therapy followed non-small-cell lung cancer and breast cancer. The cost for bevacizumab s research and development was 2.25 billion. 

Berger A.C., Sigurdson E.R., LeVoyer T., Hanlon A., Mayer R.J., Macdonald J.S., Catalano P.J., Haller D.G. (2005) Colon cancer survival associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol23, 8706-8712. 

Schumacher P., Dineen S., Barnett C., Fleming J., Anthony T. (2007) The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg 194, 827-832. 

It was significantly effective when used in combination with fluorouracil-based chemotherapy and led to the improvement of overall response rates, time to progression, and survival of patients with metastatic colon cancer (55,57,58). Bevacizumab and irinotecan, fluorouracil, leucov-orin (IFL) chemotherapy regimen showed an increase in median survival by 4.7 months, in progression free survival by 4.36 months, and in overall response rates (complete and partial responses) by 10.2% when compared with IFL plus placebo. 

Selzner, M., Bielawska, A., Morse, M.A., Rudiger, H.A., Sindram, D., Hannun, Y.A., Clavien, P-A. 2001. Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer. Cancer Res. 61, 1233-1240. 

Mrs KT, a 52-year-old hospital cleaner, is admitted as an inpatient to your oncology ward with symptoms from advanced colon cancer. Her GP referred her to the hospital oncology team three weeks ago for investigations (including colonoscopy and subsequent biopsy of a colonic mass, as well as whole body computerised tomography (CT) scan) that revealed stage IV metastatic colon cancer. Her consultant oncologist has now admitted her for FOLFOX systemic cytotoxic chemotherapy treatment. 

Every Monday in your oncology outpatient department, you run a pharmacist/ nurse-led oral capecitabine clinic, where patients are referred to you by oncologists for pretreatment counselling, drug history-taking and supplementary chemotherapy prescribing (under set clinical management plans) for the adjuvant treatment of colon cancer or treatment of metastatic colorectal cancer. 

Further investigation had confirmed a recurrence of her colon cancer, with metastatic spread to the lungs and liver. 

Hannun YA, Clavier PA. Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic 159. human colon cancer. Cancer Res. 2001 61 1233-1240. 

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