Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF) is a semisynthetic illudin analog with broad in vitro anti-neoplastic activity. In this leukemia phase I study, we investigated the toxicity profile and activity of Irofulven in patients with primary refractory or relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS). Irofulven was given as an intravenous infusion over five minutes daily for five days. The starting dose was 10 mg/m2/day (50 mg/m2/course). Courses were scheduled to be given every 3-4 weeks according to toxicity and antileukemic efficacy. Twenty patients [AML: 17 patients; MDS: one patient; ALL: one patient; mixed lineage acute leukemia: one patient] were treated. Nausea, vomiting, hepatic dysfunction, weakness, renal dysfunction, and pulmonary edema were dose limiting toxicities, occurring in two of five patients treated at 20 mg/m2/day and two of three patients treated at 12.5 mg/m2/day. The MTD was defined as 10 mg/m2/day for five days. One patient with primary resistant AML achieved complete remission. Proposed phase II studies will further define the activity of Irofulven in patients with better prognosis AML and in other hematological malignancies, both as a single agent and in combination regimens, particularly with topoisomerase 1 inhibitors.
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PMID:Phase I study of irofulven (MGI 114), an acylfulvene illudin analog, in patients with acute leukemia. 1129 29

A liver tumor metastatic from a sigmoid colon carcinoma was diagnosed in a 70-year-old man. Because hepatectomy was not indicated, the patient was treated with a combination of oxaliplatin, levofolinate, and fluorouracil (5-FU) (modified FOLFOX 6 regimen). After 15 cycles of chemotherapy, this regimen was considered to have been ineffective; therefore, treatment was started with the topoisomerase inhibitor irinotecan and an intravenous infusion of 5-FU and levofolinate (FOLFIRI). After receiving irinotecan and levofolinate, the patient had chills, a severe cough, and dyspnea. We diagnosed pulmonary edema as a side effect due to oxaliplatin, and the chemotherapeutic regimen was changed from FOLFIRI to FOLFOX plus bevacizumab. After the third cycle of oxaliplatin and levofolinate, pulmonary edema recurred, and a preshock state developed again. We suspected that either oxaliplatin or irinotecan had caused the pulmonary edema and, therefore, administered levofolinate, 200 mg/m(2); 5-FU, 400 mg/m(2); and bevacizumab, 330 mg/m(2); intravenously on day 1, followed by 5-FU, 2,400 mg/m(2), as a continuous intravenous infusion at 46 hours without either of oxaliplatin, levofolanate, and bevacizumab. After being treated with levofolinate again, the patient suddenly complained of severe dyspnea; this symptom confirmed that levofolinate had caused the pulmonary edema. To our knowledge, severe pulmonary edema caused by levofolinate has not been reported previously. This adverse effect was clinically significant because it led to the patient's death.
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PMID:Pulmonary edema caused by levofolinate treatment in patients with liver metastases from colorectal cancer. 2441 19