Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.
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PMID:Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872). 157 44

Thirty children with refractory acute lymphocytic leukemia (ALL) were treated with mitoxantrone, 8 mg/m2/day, for 5 days. Three children received a second course of the drug 3 to 4 weeks later. All but two patients had received prior anthracycline therapy. There were 2 complete responses, 4 early deaths, and 24 patients with persistent leukemia. Of the 21 patients with circulating blasts at the start of mitoxantrone who did not achieve remission, 16 (76%) had complete clearance of their peripheral blood blasts. Although all patients developed profound neutropenia (less than 100 per mm-3), mucosal and hepatic toxicities were uncommon and mild. Mitoxantrone has moderate activity in childhood ALL and should be considered for further trials in less heavily pretreated patients.
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PMID:Phase II trial of mitoxantrone in acute lymphocytic leukemia of childhood. A Pediatric Oncology Group study. 178 26

Mitoxantrone (Novantrone, American Cyanamid Company; NO) and high-dose cytarabine (Ara-C; AC) have each been shown to be active in non-Hodgkin's lymphomas (NHL) in various studies. The studies reported here are sequential. The first study (NOAC I) combined high-dose cytarabine (3 g/m2/12 h as a 3 h infusion on day 1) with mitoxantrone (10 mg/m2/d on days 2 and 3). Of 31 patients with relapsed and refractory NHL, 7 achieved complete remission (CR) and 7, partial remission (PR). Myelosuppression was the major toxicity of this regimen. In the second study (NOAC II), the dosage of cytarabine was escalated to 3 g/m2/12 h on days 1 and 2 (4 doses) while mitoxantrone remained 10 mg/m2/d on days 2 and 3. The effects of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) were simultaneously studied. Twenty-three patients from five centers were treated with NOAC plus rhGM-CSF while 14 patients from four centers received NOAC II alone. A CR was achieved in 9 of 23 patients who received the additional rhGM-CSF and in 2 of 14 patients treated with NOAC alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nL) after chemotherapy was 8 days versus a median of 13 days without rhGM-CSF, while the duration of severe thrombocytopenia (less than 20/nL) was not significantly different. The rates of infection and mucositis were 25% and 17%, respectively, with rhGM-CSF compared to 53% and 60% without rhGM-CSF. Thus, this last nonrandomized pilot study indicates that administration of rhGM-CSF reduces the duration of chemotherapy-induced cytopenia and the rate of mucositis. This growth factor does not appear to result in stimulation of lymphoma cells. At present, a controlled randomized trial is being conducted using NOAC II with rhGM-CSF or placebo to establish the definitive role of this growth factor in the treatment of NHL.
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PMID:Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin's lymphoma. 225 18

Mitoxantrone (Novantrone, NO) and high-dose cytarabine (Ara-C, AC) have each been shown in monotherapy trials to be active in non-Hodgkin's lymphoma (NHL). In the current study, a combination of the two drugs (NOAC) was administered to 31 patients with advanced NHL refractory to modern sequential chemotherapy regimens. Ara-C was administered at 3 g/m2 as a 3 hour infusion every 12 hours on day 1 (2 doses) and mitoxantrone at 10 mg/m2/day on days 2 and 3. Of the 18 patients with high-grade malignant NHL, six have attained a complete remission (CR) and two, a partial remission (PR). One CR and 5 PRs were achieved among the other 13 patients with intermediate or low-grade NHL. The median time to relapse (TTR) of patients achieving CR was 7 months with a range from 4 to 17 months. Myelosuppression with subsequent infections was the major toxicity of this regimen. The median duration of severe neutropenia (less than 0.5/nl) was 9 days with a range of 0 to 27 days and the median duration of severe thrombocytopenia (less than 20/nl), 5 days with a range of 0 to 35 days. Infectious complications during cytopenia was seen in 45.3% of the courses administered and fever of unidentified origin was seen in 42.3%. About 63% of the patients were hospitalized for intravenous antibiotic or antimycotic treatment. Other side effects were mild and included nausea, stomatitis, and transient tachycardia of greater than 100/min. Thus, this regimen was active in refractory NHL with poor prognosis, and the toxic side effects were not excessive. Evaluation of the activity of this regimen at higher dose levels of Ara-C is warranted.
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PMID:Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma. 277 3

Twenty-three patients (16 male, seven female) with hepatocellular carcinoma (HCC) were treated by hepatic arterial infusion (HAI) of mitoxantrone every 4 weeks. At each treatment, a catheter was inserted percutaneously into the main hepatic artery via the femoral artery under image intensification. Treatment consisted of a 24-hour continuous HAI of mitoxantrone, 6 mg/m2/d X 3 (eight patients) or 10 mg/m2/d X 3 (14 patients) without heparin. Eight patients had only one infusion, nine patients four infusions, five patients three infusions, two patients two infusions, and one patient five infusions. A partial response was seen in six patients, with a median duration of 20 weeks (range, 18 to 38 weeks). Five patients achieved stable disease, with a median duration of 20 weeks (range, 11 to 42 weeks). The median survival of the overall group was 22 weeks. Survivals of responding, stable, and nonresponding patients were 32 weeks, 24 weeks, and 9 weeks, respectively. Complications of catheter placement included asymptomatic dissection of the hepatic artery (one patient), and asymptomatic thrombosis of the hepatic artery (five patients). Three patients experienced mild nausea and vomiting, and six patients had mild to moderate alopecia. Granulocytopenia was frequent at both dose schedules. The granulocyte nadir was greater than 1,000/microL in 34% of evaluable courses, 500 to 1,000/microL in 32%, and less than 500/microL in 34% of courses. Two patients developed neutropenia-associated fever. A platelet nadir below 100,000/microL was seen after only 10% of courses, and only two patients had platelets below 50,000/microL. Seven patients received doxorubicin after progression on mitoxantrone. Four received systemic doxorubicin, 50 mg/m2, and three HAI of doxorubicin, 25 mg/m2, for three days. Two patients achieved partial response (18 weeks and 32 weeks) to HAI doxorubicin. Mitoxantrone has activity in HCC and is well tolerated when administered by HAI. It is not entirely cross-resistant with doxorubicin.
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PMID:Hepatic arterial infusion of mitoxantrone in the treatment of primary hepatocellular carcinoma. 303 Dec 27

Mitoxantrone (MIT) has recently been introduced into cancer therapy as a possible substitute for the structurally related drug, adriamycin (ADR), because it causes less cardiotoxicity and fewer gastrointestinal side effects. However, the dose-limiting toxicity of MIT is pronounced neutropenia. The in vitro hematoxicity of both drugs in granulocyte-macrophage precursor cells (GM-CFCs) was analyzed using drug-exposure schedules analogous to the principles of the in vivo pharmacokinetics of MIT. Bone-marrow and peripheral-blood cells were exposed to 0.075-20 ng/ml MIT or ADR for 5, 20, 60, and 120 min, and for 14 days. The 14-day exposure resulted in Do values of 0.95 and 0.68 ng/ml for bone-marrow and peripheral-blood GM-CFCs subjected to MIT. Exposure to ADR resulted in Do values of 5.43 and 5.13 ng/ml, respectively. As was the case after 14-day exposure to MIT or ADR, short-term exposure again revealed that peripheral-blood GM-CFCs were more sensitive to both drugs. Moreover, at low concentrations, ADR was less toxic than MIT in both types of GM-CFCs, but was more toxic than MIT when a concentration of 20 ng/ml was used. The intracellular concentration of MIT, as measured by high-performance liquid chromatography, was constantly below 1 ng per 2 X 10(7) cells, even when it was applied at a concentration of 20 ng/ml for an exposure time of 2 h. The fact that such low concentrations of MIT are toxic for hemopoietic precursor cells may explain the myelotoxicity of this drug. However, the difference between the precursor-cell toxicity of MIT and that of ADR was small when their respective therapeutic doses were taken into consideration. Further analyses of their toxicity in stem cells and/or the microenvironment would appear to be needed.
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PMID:Comparative in vitro toxicity of mitoxantrone and adriamycin in human granulocyte-macrophage progenitor cells. 362 56

Nineteen out of 62 evaluable patients with advanced breast cancer achieved an objective tumour response to mitoxantrone (31%) given in a dose of 12-14 mg/m2 by i.v. infusion repeated at 3-weekly intervals. The response rate in patients who had received no prior chemotherapy for advanced disease was 35%, compared with 22% in previously treated patients. Median duration of response was 10 months. Responses were seen in three out of nine patients who failed to respond to adriamycin. Neutropenia was dose limiting and eight out of 65 patients evaluable for toxicity had a neutropenic infection. Two patients developed readily reversible cardiac failure and two more developed physiological features of cardiac impairment, all after prolonged treatment. Other toxicities were mild and the drug was well tolerated; severe alopecia occurred in only one patient. Nine patients treated with a combination of mitoxantrone, vincristine and methotrexate all developed leukopenia with a mean white blood count of 1400/mm2 (range 200-2400) although no episodes of neutropenic infection were seen and the combination was otherwise well tolerated. Mitoxantrone is an active, well tolerated drug in the treatment of advanced breast cancer and merits further evaluation.
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PMID:Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer. 666 33

Sixty-five patients with advanced breast carcinoma were treated with mitoxantrone, an anthracenedione with structural similarities to adriamycin. The series included 26 patients who had received no prior chemotherapy. Treatment was given in a dose of 12-14 mg/m2 by IV infusion, repeated every 3 weeks. Sixty-two patients were evaluable for response, but all were evaluable for toxicity. One (2%) achieved a complete response and 18 (29%) a partial response (overall response rate 31%). The response rate in patients who had received no prior chemotherapy was 35%, vs 22% in previously treated patients. The median duration of response was 10 months (range 3.5-18.5 months). Two responders had previously failed to respond to adriamycin, and a third responder subsequently failed to respond to adriamycin. Neutropenia was the most frequently seen toxicity, with a WBC of less than 2,000/mm3 seen in 26 patients (40%), eight of whom (12%) had a neutropenic infection. Thrombocytopenia (less than 100,000/mm3) occurred in 12 patients (18%), but in three of these only after at least 6 months of treatment. Two patients developed readily reversible cardiac failure after prolonged treatment (11-13 months). Other toxicities were in general mild, and the drug was well tolerated: severe alopecia occurred in only one patient. Mitoxantrone is an active well-tolerated agent in the treatment of advanced breast carcinoma, but the risk of neutropenia requires careful supervision. The long-term risk of cardiotoxicity cannot yet be fully assessed.
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PMID:Mitoxantrone: an active new agent in the treatment of advanced breast cancer. 669 66

Thirty-one patients with measureable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received dihydroxyanthracenedione (DHAD, NSC 301739) on a 5-day I.V. schedule administered every 4 weeks. Good-risk patients received DHAD at the starting daily dose of 4 mg/m2 while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 3 mg/m2. There were no complete or partial remissions in this study. Eight of 30 evaluable patients had disease stabilization. The dose-limiting toxic effect was myelosuppression; neutropenia was more severe than thrombocytopenia. The myelosuppression was more severe in patients who had poor bone marrow reserves and abnormal pretreatment liver functions (serum alkaline phosphatase and serum glutamic oxaloacetic transaminase) levels greater than or equal to 1.5 times normal). DHAD administered by the 5-day dose schedule as used in this study is not effective against colorectal cancer.
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PMID:Phase II evaluation of dihydroxyanthracenedione (DHAD, NSC 301739) in patients with metastatic colorectal cancer. 683 6

Twenty-nine patients with measurable metastatic upper gastrointestinal cancer received dihydroxyanthracenedione (DHAD, NSC 301739) on a 5-day I.V. schedule administered every 4 weeks. Good-risk patients received DHAD at the starting daily dose of 4 mg/m2, while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 3 mg/m2. Most of the patients had disease refractory to 5-Fu-adriamycin-mitomycin-C-containing regimens. Eight of 25 patients evaluable for response had received no prior chemotherapy. There were no complete or partial remissions in this study. Stabilization of disease occurred in six of 14 patients with gastric carcinomas and five of 10 patients with pancreatic carcinomas. The dose-limiting toxic effect was myelosuppression; neutropenia was more severe than thrombocytopenia. The myelosuppression was more severe in patients who had poor bone marrow reserve and liver function impairment. These results suggest that DHAD administered by the 5-day dose schedule as used in this study is not very effective against gastric and pancreatic carcinomas.
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PMID:Phase II evaluation of dihydroxyanthracenedione (DHAD, NSC 301739) in patients with upper gastrointestinal tumors. A preliminary report. 686 18


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