Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.
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PMID:[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. 782 85

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

Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.
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PMID:Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer. 2187 14