Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Teniposide and etoposide are third-generation semi-synthetic derivatives of epipodophyllotoxin. Following the initial clinical introduction of teniposide in the 1970s, investigations focused almost exclusively on its analogue, etoposide, because of its formulation, which was felt to have advantages in addition to oral administration. Despite consistently inadequate dosing and scheduling, early phase I and II trial results with teniposide were promising, and current trends encourage a second look. The substantial antitumor activity of teniposide is comparable with that of etoposide, and clinical interest was rekindled when it was shown to have considerable activity against small cell lung cancer (SCLC). In view of the inadequacy of early trials and the premature cessation of clinical study, it is recommended that teniposide be reevaluated for its activity against malignant lymphomas, Hodgkin's disease, leukemias, and SCLC, against all of which its early results were encouraging. In addition, consideration should be given to its activity against brain tumors, neuroblastomas and other childhood solid tumors, and ovarian cancer; its potential value against gastric, hepatocellular, breast, and bladder cancers also should be investigated. Other areas that warrant further study include elucidation of the exact mechanism of action of teniposide, its role in both single- and multiple-agent chemotherapeutic regimens, and resolution of its optimal dose and schedule. Finally, it is suggested that with new routes of administration and improved formulations, teniposide may be expected to play a significant role in the treatment of malignant lymphomas, SCLC, and pediatric lymphocytic leukemia and neuroblastoma.
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PMID:Teniposide in adult solid tumors: a historical perspective. 141 38

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