Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irinotecan (CPT-11) is a novel water-soluble, semisynthetic derivative of camptothecin, with inhibitory effects on mammalian DNA topoisomerase I, high cytotoxic activity in vitro and anticancer activity in animal models. Fifty-nine patients, with cancer refractory to conventional therapy, were entered in this phase I study, using a weekly schedule administration. A total of 304 weekly doses were administered at dose levels ranging from 50 to 145 mg/m2 (30-90 min i.v. infusion). Leukoneutropenia and diarrhea were the dose-limiting toxicities and appeared to be dose related, reversible and noncumulative. However, interpatient variability of toxic effects was substantial. Prolongation of the infusion time from 30 min to 90 min appeared to decrease the diarrhea. Other toxicities included moderate emesis, asthenia, alopecia, abdominal pain, and anemia. CPT-11 plasma disposition was bi- or triphasic with a terminal half-life of 9.3 h. CPT-11 area under the plasma concentration versus time curves increased linearly with dose (r = 0.47, P < 0.01). The active metabolite area under the plasma concentration versus time curve correlated significantly with that of CPT-11, but not with that of CPT-11 dose. Both CPT-11 and 7-ethyl-10-hydroxycamptothecin areas under the plasma concentration versus time curve correlated significantly with leukoneutropenia and diarrhea. One partial and 4 minor responses were observed at dose levels of 130 and 145 mg/m2. Using this weekly schedule, recommended doses for phase II studies are 100 mg/m2 in high risk patients and 115 mg/m2 in others.
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PMID:Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. 804 82

It is wellknown that cholinomimetic side effects, such as sedation, abdominal pain, nasal flow and watery eyes, may develop in patients in the early stage of Irinotecan (CPT-11) administration; however, there have been no investigations concerning methods for preventing the development of these side effects. To assess the protective effects of pre-treatment with d-CM on cholinomimetic side effects in the early stage after Irinotecan (CPT-11) administration, we prescribed d- Chlorpheniramine maleate (d-CM) to a group of patients prior to Irinotecan (CPT-11) administration. Twenty members from the group of non-d-CM-treated patients (n=39) and 4 members from the group of treated patients (n=20) complained of side effects. The pre-administration of d-CM significantly reduced the number of patients with side effects (p<0.05). The relative risk (RR) for the frequency of side effects was 0.39 (95% CI; 0.15-0.98), demonstrating that the frequency of side effects was significantly reduced. Based on theses findings, we concluded that the pre-administration of d-CM had protective effects against side effects that might develop in the early stage after Irinotecan (CPT-11) administration.
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PMID:[Protective effects of d-chlorpheniramine maleate pre-treatment against acute side effects of Irinotecan(CPT- 11)]. 2177

Oxaliplatin is a common chemotherapy drug used for colon and gastric cancers. Common side effects are peripheral neuropathy, hematological toxicity, and allergic reactions. A rare side effect is seizures which are usually associated with posterior reversible leukoencephalopathy syndrome (PRES). A 50-year-old male patient presented with severe abdominal pain. CT scan of the abdomen showed acute appendicitis. Appendectomy was done and pathology showed mixed adenoneuroendocrine carcinoma. Adjuvant chemotherapy was started with Folinic acid, Fluorouracil, and Oxaliplatin (FOLFOX). During the third cycle of FOLFOX, the patient developed tonic-clonic seizures. Laboratory workup was within normal limits. EEG and MRI of the brain showed no acute abnormality. The patient was rechallenged with FOLFOX but he had tonic-clonic seizures for the second time. His chemotherapy regimen was switched to Folinic acid, Fluorouracil, and Irinotecan (FOLFIRI). After 5 cycles of FOLFIRI, the patient did not develop any seizures, making Oxaliplatin the most likely culprit for his seizures. Oxaliplatin-induced seizures rarely occur in the absence of PRES. One case report has been described in the literature. We present a rare case of tonic-clonic seizures in a patient receiving Oxaliplatin in the absence of PRES.
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PMID:Oxaliplatin-Induced Tonic-Clonic Seizures. 2649 86