Irinotecan

Irinotecan (also known as CPT-11) is a semisynthetic derivative of the natural alkaloid camptothecin which antagonizes the activity of topoisomerase I. Topoisomerase I plays a key role in replication by relaxing the supercoiled DNA helix with reversible and transient single stranded DNA breaks. Following conversion to irinotecan's active metabolite, SN-38, these transient breaks are stabilized resulting in replication arrest and apoptosis. The major toxicity of irinotecan is delayed onset diarrhea. An acute cholinergic syndrome characterized by diaphoresis, salivation, lacrimation, abdominal cramps, and bradycardia, may be observed during administration and typically responds to atropine (Takasuna et al, 1996). When compared to infusional 5-FU in patients who progressed on first line bolus 5-FU, irinotecan resulted in an improved overall survival and time to progression (4.2 vs 3.9 months, p = .030) (Rougier et al, 1997). A second study by Cunningham and colleagues (1998) showed an improved overall survival of 9.2 vs 6.5 months (p = .0001) with irinotecan vs best supportive care alone. Two subsequent studies established the combination of irinotecan with 5-FU/LV as an important combination for patients with advanced CRC (Table 97-1). Concerns regarding toxicity with the weekly schedule of irinotecan and bolus 5-FU/LV (IFL) were raised due to an unexpected number of early deaths in two cooperative group studies involving IFL (Rothenberg et al, 2001). The majority of deaths were attributed to GI toxicities or thromboembolic events, prompting recommendations for close clinical monitoring and early supportive intervention for patients treated with IFL.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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