Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between March 1980 and December 1981, 22 patients were treated with 4'(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA), each given by I.V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced. The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1-23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission. Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I.V. hyperalimentation. We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL. Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.
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PMID:4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia. 619 61

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.
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PMID:Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party. 875 14