Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current report presents the data of the Division of Cancer Treatment of the National Cancer Institute (NCI) on the antitumor activity of the anthracycline antibiotic 4'-epidoxorubicin in experimental tumor systems. Direct comparisons are made with doxorubicin in individual experiments, and the data are related to those of earlier studies in the form of a review of experimental activity, in order to assess the relative activity of 4'-epidoxorubicin and doxorubicin. The experimental test models utilized by the NCI for these studies included the leukemias P388 and L1210, B-16 melanoma, Lewis lung carcinoma, the colon tumors 26 and 38, and the mammary tumors CD8F1 and C3H16/C. The human tumors growing in xenograft in athymic mice included the models LX-1 lung tumor, CX-1 colon tumor, and MX-1 mammary tumor. Additional comparisons were made with the tumor models Gross leukemia, sarcoma 180, MSV-induced sarcoma, MS-2 tumor, and a variety of human tumors growing in athymic mice, as well as with in vivo toxicologic and in vitro cytotoxicity models. Although for 4'-epidoxorubicin there is only a minimal alteration of the configuration of the doxorubicin molecule, quantitative comparison of 4'-epidoxorubicin and doxorubicin revealed not only similarities but also differences in biological activity. Both drugs showed activity against a broad spectrum of experimental tumors, with 4'-epidoxorubicin more effective against some tumors and equally effective against others. 4'-Epidoxorubicin evidenced less toxicity than doxorubicin in both acute and chronic toxicity studies with retention of therapeutic effectiveness and showed reduced cardiotoxicity. With 4'-epidoxorubicin there resulted a higher therapeutic index and therapeutic ratio, permitting the use of higher dosage and a greater margin of safety. The preclinical differences in therapeutic and toxicologic manifestations of 4'-epidoxorubicin, reflecting apparent alterations in pharmacologic properties and mode of action in comparison with doxorubicin, support the broad spectrum clinical trials of this already-demonstrated clinically active drug.
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PMID:The effectiveness of the anthracycline analog 4'-epidoxorubicin in the treatment of experimental tumors: a review. 388 88

Epidoxorubicin (EDX) was administered to a group of 26 patients with acute leukaemia or lymphoma, replacing either daunorubicin or doxorubicin (DXR) as a component of multiple-chemotherapy regimens. In 10 patients with acute non-lymphocytic leukaemia treated at presentation, 5 complete and 4 partial remissions were obtained. All patients with lymphoma of different types responded at least partially: in a group of 14 cases, 8 in relapse and 6 at presentation, there were 10 complete and 4 partial remissions. It is of interest that such results were obtained in patients of high median age with dosages of EDX much lower than those employed for DXR.
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PMID:A pilot study of epidoxorubicin (NSC 256942) in combination treatment of acute leukaemia and non-Hodgkin's lymphoma. 639 Feb 86

The tAnGo trial is a randomized, open-label, multicenter phase III trial examining adjuvant treatment with epirubicin (Ellence)/cyclophosphamide (Cytoxan, Neosar) for four cycles followed by paclitaxel alone or combined with gemcitabine (Gemzar) for four cycles in patients with early-stage breast cancer. In the Cancer and Leukemia Group B (CALGB) 9344 trial, addition of paclitaxel to anthracycline/cyclophosphamide adjuvant therapy resulted in increased time to recurrence and improved survival. Because an unplanned subgroup analysis in CALGB 9344 indicated a significant benefit of paclitaxel in patients with estrogen receptor (ER)-negative disease but not ER-positive disease, the initial tAnGo trial design called for enrollment of patients with ER-negative disease. The tAnGo trial entry criteria were recently amended to allow any ER status, given experience suggesting that clinical benefit of taxane-containing regimens in ER-positive disease may emerge over a time frame longer than that required to detect benefit in ER-negative disease. Gemcitabine has been included as a partner for paclitaxel in the tAnGo trial based on high response rates, including high complete response rates, observed in phase II trials of the combination in more advanced disease and based on the tolerability and safety of the combination compared with those of other taxane-containing two-drug combinations. The tAnGo trial is currently accruing patients and has a target population of 3,000. Trial results should provide important information on the role of gemcitabine in adjuvant therapy for breast cancer.
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PMID:Adjuvant chemotherapy for early-stage breast cancer: the tAnGo trial. 1568 22