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

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

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

Metoclopramide is very useful in hematology. This French drug has been continuously used for twenty years as a powerful inhibitor of nausea and vomiting induced by numerous antineoplastic associations. When administered intravenously in patients under sequential chemotherapy for leukemia or lymphoma, metoclopramide prevents digestive discomfort. After each infusion, the ingestion of solution or tablets prolongs the antiemetic action for several hours without any side-effects. Conversely, corticosteroid therapy is well tolerated in ulcerous and gastritic patients and tolerance is preserved in others when they are submitted for the first time to high doses of metoclopramide, because of the acceleration of gastric evacuation.
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PMID:[Metoclopramide in hematology]. 629 Nov 61

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.
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PMID:Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma. 636 49

A total of 47 patients with relapsed or primarily refractory leukemia were treated with mitoxantrone alone or in combination with vincristine sulfate and prednisone or cytarabine. Eligible patients included those with adequate renal and hepatic function, normal left ventricular ejection fraction, and those who had received previous treatment. When mitoxantrone was given alone in a once daily times five schedule, 5 of 12 acute lymphoblastic leukemia patients achieved complete remission; 4 of these patients had been refractory to reinduction and 1 to induction chemotherapy with anthracycline-containing treatments. Four of these patients had progressive disease, and three died during induction. Of 12 patients with acute myeloid leukemia, 1 had a complete remission, 1 had a partial remission, 8 had progressive disease, and 2 died during induction. Mitoxantrone was also found to be active in two patients in the blastic transformation of chronic myeloid leukemia with a response in one patient lasting 17 weeks. Combinations of mitoxantrone with vincristine sulfate and prednisone resulted in complete remission in four of nine acute lymphoblastic leukemia patients and one of four patients with Tdt-positive chronic myeloid leukemia in blast crisis. Three of these patients had not experienced a prior remission following anthracycline-containing treatments. Partial remission occurred in two of the acute lymphoblastic leukemia patients and one of the Tdt-positive chronic myeloid leukemia patients. Two of this latter group of patients died in induction. Treatment with mitoxantrone and cytarabine resulted in two acute myeloid leukemia patients achieving complete remission and one a partial remission; two patients had progressive disease, and one died in induction. No response was seen in a patient with Tdt-negative chronic myeloid leukemia after two courses of treatment. One patient with acute leukemia in the course of myelofibrosis died in induction. All the patients achieving complete remission are alive and have been in complete remission from 2 to 12 months. Side effects included mild nausea and vomiting in 9 of 13 patients treated with the mitoxantrone-vincristine sulfate-prednisone combination, and in 3 of 8 patients treated with the mitoxantrone-cytarabine combination. Other side effects of the combination treatments include drug-induced oral mucositis (of a lesser degree than with mitoxantrone alone), transient hepatic abnormalities, and infectious complications, such as sepsis, Candida sp colonization of the upper digestive tract, and soft tissue cellulitis, in a few patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mitoxantrone as a single agent and in combination chemotherapy in patients with refractory acute leukemia. 638 64

Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drug-related gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia.
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PMID:Mitoxantrone in the treatment of relapsed and refractory acute leukemia. 638 65

Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4-9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2-3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR + PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.
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PMID:Phase II trial of aclacinomycin A in acute leukemia and various solid tumors. 657 90

m-AMSA, an acridine dye derivative, has been utilized in 36 patients with advanced hematologic malignancies. In 22 patients with lymphoma receiving 120 mg/m2 every 3 weeks, 10(45%) have achieved remissions. Eight of these remissions have been partial. The median duration of remission in patients with lymphoma was 3 months (range 1-12+ months). In 11 patients with acute leukemia receiving m-AMSA, 40 mg/m2 t.i.d. for 5 days, three (27%) have achieved remissions. Two of the three remissions have been complete. All three remissions in patients with leukemia were sustained for 1 month. Two patients with myeloma and one patient with chronic lymphocytic leukemia failed to respond. The major toxicity of m-AMSA has been myelosuppression. The dose-limiting toxic effect in patients with lymphoma was neutropenia. Nausea and vomiting, alopecia, phlebitis, and hepatic dysfunction have been noted in a minority of patients. Phlebitis appeared to be prevented with heparin administration after m-AMSA infusion. One fatal arrhythmia occurred, apparently related to therapy. m-AMSA appears active in advanced leukemia and lymphoma. Further studies are merited, particularly in combination with known effective agents, in order to improve upon remission duration.
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PMID:m-AMSA: phase II trial in advanced lymphoma and leukemia. 658 46

Aclarubicin (ACR) was administered in a prospective cooperative phase II trial to 44 patients with possibly refractory acute nonlymphocytic leukemia who were previously treated with daunorubicin and cytarabine. Induction treatment consisted of 80 mg/m2 of ACR iv daily for 3 days, followed by 80 mg/m2 iv daily for 2 days in patients not obtaining a complete remission (CR) after 2-4 weeks. CR was observed in eight patients (18%) and partial remission was observed in six (14%). On monthly maintenance chemotherapy with ACR and cytarabine, the duration of CRs varied between 10 and 58 weeks. Achievement of remission was not related to age, presence or absence of Auer bodies, cytogenetic characteristics, or previous response to daunorubicin and cytarabine. Side effects were nausea and vomiting observed in 86% and diarrhea in 34% of the patients, whereas mucositis and alopecia were uncommon. Disturbances of cardiac function arousing suspicion of acute ACR toxicity were observed in seven patients. No case of chronic cardiotoxicity was observed, despite the fact that 20 patients received ACR doses greater than 400 mg/m2, with seven of the 20 having had a previous daunorubicin dose greater than 400 mg/m2. As CR was obtained in four of 14 patients with primary therapy-resistant leukemia and in two of 16 patients with relapse and no response to re-treatment with daunorubicin and cytarabine, ACR does not seem to show clinical cross-resistance to daunorubicin. Evaluation of ACR in first-line chemotherapy of acute nonlymphocytic leukemia appears justified.
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PMID:Aclarubicin in the treatment of acute nonlymphocytic leukemia refractory to treatment with daunorubicin and cytarabine: a phase II trial. 659 2

The physiological pyrimidine nucleoside thymidine (dThd) is cytotoxic to normal and neoplastic cells in culture that are exposed to concentrations in excess of 1 mM for prolonged periods. In order to explore the antileukemic potential of the compound, we have treated six patients with relapsed leukemia or lymphoma with marrow and blood involvement, by prolonged infusions of dThd, at dosages of 90 to 240 g/sq m/day for 14 to 29 days. Mean plasma dThd concentration ranged from 3.8 to 5.5 mM. Cerebrospinal fluid levels were measured on three occasions and ranged from 2 to 23.5% of simultaneous plasma levels. Diarrhea was dose limiting in one patient. The other side effects included nausea and vomiting in all patients, hepatotoxicity in two patients, electrolyte imbalance in one, progression of a pericardial effusion to tamponade in one, and mild central nervous system toxicity in five. In all cases, this therapy produced bone marrow aplasia. One patient with acute lymphoblastic leukemia, refractory to prior treatment, achieved a complete remission which lasted for 16 weeks. Another patient with lymphoblastic lymphoma had a greater than 50% reduction in his mediastinal mass which lasted for less than 1 month. At multiple points during therapy, the bone marrow S-phase fraction was measured by flow cytometry and autoradiography. In five patients, the proportion of cells in S phase increased during the first few days of the infusion but then returned to base line, concomitant with an overall reduction in the number of bone marrow blasts. Cytoreduction was evaluated by the technique of W. Hiddemann, B. D. Clarkson, T. Buchener, M. R. Melamed, and M. Andreeff (Blood, 59: 216-225, 1982). The magnitude of tumor cell kill ranged from 0.7 to 3.6 logs of blasts/cu mm of bone marrow. The data demonstrate that dThd is able to induce a complete remission in a patient with acute leukemia previously refractory to treatment. However, because of the very large drug quantities, fluid volumes, and the prolonged course required to produce the necessary tumor cell kill, this treatment approach is too impractical to be used extensively.
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PMID:Effect of very high-dose thymidine infusions on leukemia and lymphoma patients. 671 7


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