Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epipodophyllotoxins, etoposide and teniposide, have been used in leukemias and malignant lymphomas for the past 15 years. Although etoposide has acquired a place in many first-line protocols for lymphomas and, more recently, for leukemias, the role of teniposide has remained limited. Teniposide is a more potent inhibitor of topoisomerase II than etoposide, and has a less toxic effect on hematopoietic progenitor cells. Both drugs have been regarded as equitoxic and cross-resistant. The role of teniposide in front-line treatment of leukemias has only been established in childhood acute lymphoblastic leukemia (ALL). Some promising results have been obtained in small numbers of patients with refractory adult ALL and acute monoblastic leukemia. However, the remission rates and remission duration were not significantly different from those of other combination regimens. Data on teniposide in untreated acute nonlymphoblastic leukemia are very scarce. In non-Hodgkin's lymphoma, the antineoplastic activity of teniposide has been demonstrated in studies by the European Organization for Research and Treatment of Cancer and in two large studies conducted by the Australian and New Zealand Lymphoma Co-operative Chemotherapy Study Group. In these studies, teniposide had comparable but not significantly better activity than vincristine. The dose-dependent antineoplastic activity of teniposide has led to its use in several conditioning regimens in bone marrow transplantation for leukemias and lymphomas. The limited clinical data currently available on teniposide seem to warrant further clinical trials with this agent in leukemias and lymphomas.
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PMID:Teniposide in lymphomas and leukemias. 141 40

Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble derivative of etoposide, a semisynthetic podophyllotoxin that is important in the treatment of a variety of malignancies, including lung cancer, germ cell tumors, non-Hodgkin's lymphoma, Hodgkin's lymphoma, acute leukemia, etc. Because etoposide is poorly water soluble, it must be dissolved in a polysorbate 80-based solvent mixture, which is moderately allergenic and requires a large volume of saline for administration. Etoposide phosphate is water soluble and is rapidly converted in vivo to etoposide by endogenous phosphatases. Because it is water soluble, etoposide phosphate can be administered in volumes much smaller than those required with etoposide therapy, permitting rapid intravenous administration in the outpatient setting. We recently reported the results of a phase I study using etoposide phosphate on a bolus, daily x 5 schedule. Like others, we demonstrated that etoposide phosphate has pharmacokinetic properties virtually identical to those of etoposide. Our dose-finding study indicated that etoposide phosphate can be used in doses up to 100 mg/m2/d x 5 every 3 weeks in patients who have not had extensive prior chemotherapy, and that a dose of 75 mg/m2 would be appropriate for patients who had undergone multiple prior therapies or who had prior radiotherapy. The dose-limiting toxicity was neutropenia. Paclitaxel, a microtubule-stabilizing agent, is active against a variety of solid and hematopoietic malignancies that overlap with those against which etoposide is active. Because the mechanisms of action of these two agents differ, it is logical to suppose that the combination of the two agents might produce some additive effect when used to treat cancers that respond to both individual agents. We therefore undertook a phase I study using paclitaxel as a 3-hour infusion in combination with a 5-minute infusion of etoposide phosphate daily x 3 every 21 days. We used the 3-hour paclitaxel schedule because it has been shown to be less myelotoxic than longer infusions at the same doses. Our goal in this ongoing study is to determine the maximum tolerated doses of the two drugs in combination, to determine the toxicities of the regimen, and to assess its anticancer activity.
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PMID:A phase I study of etoposide phosphate plus paclitaxel. 899 73