Irinotecan Standardization

Some lymphomas, for example, are related to overexpression of Bcl-2. Antisense oligonucleotides are specially designed to target the overexpression of Bcl-2. Oblimersen (Genasense) is an antisense drug by Genta to block Bcl-2 production and enhance the efficacy of other standard chemotherapy drugs such as paclitaxel, fludarabine, irinotecan, and cyclophosphamide. 

For patients who cannot tolerate the intensity of the oxaliplatin and irinotecan regimens the standard Mayo (see Poon et al., 1989), Roswell and de Gra-mont Park 5-FU regimens (see de Gramont et al., 1997) remain appropriate. In addition the oral fluo-ropyrimidine pro-drug, capecitabine, is equally beneficial. 

This benefit comes at a cost of significant toxicity, particularly neuropathic, and more mature data are necessary to demonstrate the ultimate benefit of adjuvant therapies on improved overall survival. So far irinotecan plus 5-FU based therapy has produced disappointing results in adjuvant treatment. Despite the present lack of data addressing overall survival benefit, oxaliplatin plus 5-FU/leucovorin is widely recommended as the gold standard adjuvant therapy for stage 3 disease. For those whose medical fitness or other contra-indications preclude oxaliplatin based therapy 5-FU/leucovorin on a weekly or monthly schedule is recommended. Oral capecitabine for 6 months has recently been reported to be at least equivalent to 5-FU/leucovorin. 

Cetuximab is used for treatment of metastatic colorectal carcinoma, which expresses EGFR, in combination with irinotecan, provided that these patients are refractory to irinotecan-based standard chemotherapeutic regimen. However, in patients who could not tolerate irinotecan-based chemotherapeutic regimen, it is used as a single treatment for EGFR-expressing metastatic colorectal cancer. The doses are similar to the doses used for squamous cell carcinoma of the head and neck. 

Reversible alopecia is very common at standard doses of podophyllotoxin derivatives, starting at doses of 500 mg/ m of etoposide. It is also common even with low, continuous oral doses of etoposide (for example 50 mg/m / day). Partial or complete alopecia occurs in 12-70% of patients taking topotecan or irinotecan (123). 

Triple-drug therapy consisting of fluorouracil and leu- covorin with oxaliplatin or irinotecan improves survival compared to fluorouracil plus leucovorin alone, and is considered as standard first-line therapy for metastatic disease. Bevacizumab, in combination with fluorouracil-based chemotherapy, is also indicated for initial treatment of metastatic colorectal cancer. Patients may benefit from more than one regimen duringthe treatment of their disease. 

The results of N9741 have been debated between clinicians since their presentation. Whether an irinotecan-containing regimen (IFL or FOLFIRI) is still the standard of care for metastatic disease, or if it has been replaced by FOLFOX4 is an unanswered question. Most patients should receive irinotecan- and oxaliplatin-containing regimens at some point during treatment for their disease. 

Upon disease progression following standard initial therapy, appropriate treatment options may include oxaliplatin plus fluorouracil and leucovorin, irinotecan plus cetuximab, cetuximab, irinotecan, continuous-infusion fluorouracil, capecitabine plus irinotecan or... 

I Irinotecan. Two important trials have delineated an appropriate standard of care for patients who experience disease progression with fluorouracil therapy for metastatic colorectal cancer. The results of these trials demonstrate a survival benefit associated with irinotecan, which was approved by the FDA in 1996, as second-line therapy for recurrent or progressive disease following fluorouracil. In phase n studies of previously treated patients with metastatic colorectal cancer, objective response rates of 13% to 27% have been observed. ... 

Based on the results of these trials, irinotecan shonld be considered standard second-line therapy for patients who have failed prior treatment with fluorouracil-based regimens. Either dosage regimen (irinotecan 125 mg/m IV weekly for 4 weeks followed by a 2-week rest period or 300 to 350 mg/m IV every 3 weeks) is acceptable. For the every 3-week regimen, initial administration of irinotecan at the lower dose should be considered for patients who have received significant prior pelvic or abdominal irradiation. Protracted continnons-infusion fluorouracil could be considered for those individuals with disease that no longer responds to bolus IV fluorouracil plus leucovorin or irinotecan. 

Irinotecan is a DNA topoisomerase inhibitor. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. It is indicated in the metastatic cancer of the colon or rectum after standard treatment with fluorouracil. 

Higher response rates are seen when 5-FU is used in combination with other agents, such as cyclophosphamide and methotrexate (breast cancer), cisplatin (head and neck cancer), and with oxaliplatin or irinotecan in colon cancer. The combination of 5-FU and oxaliplatin or irinotecan has become the standard first-line treatment for patients with metastatic colorectal cancer. The use of 5-FU in combination regimens has improved survival in the adjuvant treatment for breast cancer, and with oxaliplatin and leucovorin, for colorectal cancer. 5-FU also... 

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