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)

A 60-year-old male with hepatocellular carcinoma was treated by repeated intra-arterial injection of epirubicin, carboplatin and doxorubicin. Subsequently, radiotherapy and intravenous administration of etoposide were also carried out. Thirty-three months later he developed AML (M2). The chromosome analysis revealed 45, X, -Y, t (8;21) (q22;q22), which suggested that this leukemia was induced by topoisomerase II targeting agents. He was treated with low dose BHAC and G-CSF and achieved complete remission. This leukemia may be caused by synergic effect of topoisomerase II inhibitors and carboplatin together with radiotherapy. This may be the first report of therapy-related leukemia following chemotherapy for hepatocellular carcinoma.
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PMID:[Therapy-related AML(M2) with t(8;21) that developed three years after chemotherapy for hepatocellular carcinoma]. 869 93

Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled, 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study ofsequential administration of topotecan 1.25 mg/m2 days 1-5 and etoposide 50 mg po b.i.d. days 6-12, every 28 days without G-CSF. Most patients had diffuse large B-cell lymphoma and all had received only one prior regimen (CHOP, 20 patients, or equivalent, 2 patients). Patients with stable or responding disease were allowed to proceed to high-dose therapy and autologous stem-cell transplant after 2 cycles of therapy. The 22 patients received a total of 62 cycles of topotecan + etoposide (median 2, range 1-6), and 4/22 completed all six planned cycles. Hematologic toxicity was significant and resulted in incomplete etoposide dosing in half of all cycles in 16/22 patients. Nineteen of twenty-two patients had grade 3/4 neutropenia, 12 had grade 3/4 thrombocytopenia, and 6 grade 3/4 anemia. Eleven patients had at least one episode of febrile neutropenia or had documented infection. Non-hematologic toxicity was mild. Four patients had a partial response (PR) (18.2%), nine had stable disease and seven progressed; three patients with stable disease went on to ABMT. The combination of topotecan and etoposide as given in this study has modest activity in relapsed/refractory aggressive histology NHL, and produces marked myelosuppression. Other doses and schedules combining topo I and II inhibitors, or topo I inhibitors with alkylating agents, should be explored with the addition of hematopoietic growth factors in this patient population.
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PMID:Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin's lymphoma: a National Cancer Institute of Canada Clinical Trials Group study. 1240 Jun

The combination of irinotecan (Camptosar), epirubicin, and capecitabine (Xeloda) has shown an acceptable toxicity profile. In this open-label phase I study, irinotecan was administered IV at a fixed dose of 250 mg/m2 on day 1 in combination with capecitabine at a fixed dose of 1500 mg/m2 for days 2 to 7 and epirubicin starting at a dose of 40 mg/m2 and escalating by 10 mg/m2 in cohorts of three patients for those with metastatic adenocarcinomas. With the addition of granulocyte colony-stimulating factor (G-CSF [Neupogen]) to the regimen, patients received epirubicin at clinically relevant doses after dose-escalation. Results of the topoisomerase activity will be reported with the final results of this phase I study. The dose-limiting toxicity has not yet been reached. This combination regimen in patients with upper gastrointestinal malignancies and breast cancer will be investigated as part of phase II studies, once the dose-limiting toxicity is determined. The appropriate sequencing of the regimen to maximize clinical efficacy will also be determined.
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PMID:Irinotecan, epirubicin, and capecitabine in metastatic adenocarcinomas: preliminary results of a phase I study. 1568 35

The cure rate for several solid tumour malignancies including breast cancers, head and neck cancers, bone cancers, and sarcoma has improved remarkably with the advent of neoadjuvant and adjuvant therapies. Unfortunately, exposure to chemotherapy or radiation as a part of these treatments exposes patients to the risk of subsequent myeloid malignancies. Therapy related myeloid malignancies have certain characteristic findings. They typically arise within 10 years of treatment exposure, they are seen in younger patients, and the greatest risk is in patients who receive therapy with alkylating agents or topoisomerase II inhibitors. Solid tumours whose therapies utilize these agents at higher doses, namely bone/soft tissue cancers, testicular cancer, anal cancer, and brain tumours, appear to be the groups at highest risk for T-MN. Beyond these patients, emerging populations diagnosed with T-MN include prior platinum exposure, and patients requiring G-CSF support with chemotherapy.
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PMID:Myeloid malignancies after treatment for solid tumours. 3092 74