Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.
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PMID:Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. 171 46

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.
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PMID:Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease. 201 17

The maximum tolerated dose for a combination chemotherapy regimen of Thiotepa, Mitoxantrone and Methotrexate (TMM) administered intravenously every three weeks to twelve patients with metastatic breast cancer was: Thiotepa: 15mg/m2, Mitoxantrone: 10mg/m2 and Methotrexate: 30mg/m2. The major toxicities from the combination related to myelosuppression. Partial response was seen in 5 patients, ranging in duration from 1.25 to 10 months. Four out of eight patients who had received prior doxorubicin responded. The results are encouraging and warrant further study of this combination.
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PMID:A pilot trial of TMM (thiotepa, mitoxantrone and methotrexate) chemotherapy for metastatic breast cancer. 212 30

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 is a substituted anthraquinone with considerable activity against human acute leukemia. The authors' goal was to treat patients with continuous infusion mitoxantrone in order to maintain cytotoxic steady state levels with acceptable toxicity and to assess the results. Daily mitoxantrone levels showed a mean steady state plasma level of 16.8 +/- 1.4 ng/ml (range, 9.1-25.1) with a systemic clearance of 519 +/- 47 ml/minute/m2. No drug accumulation occurred. Mitoxantrone was undetectable 24 hours postinfusion. All patients, including two patients with chronic myelogenous leukemia in blast phase, had greater than 90% reduction in leukemia cell mass (marrow cellularity X percent leukemia cells) by day 6. However, six patients received 3 days of etoposide at that point because of residual acute nonlymphocytic leukemia (ANLL). Overall four patients (36%) had a complete remission; one additional patient had a bone marrow remission but also had a persistent granulocytic sarcoma. Toxicities included severe but tolerable myelosuppression, mucositis, and hepatic dysfunction. There was no correlation between mitoxantrone levels, toxicity, or clinical response. Continuous infusion produces cytotoxic plasma mitoxantrone levels and rapid clearing of ANLL from bone marrow. Further dose escalation may be possible.
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PMID:Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia. 234 Apr 63

Mitoxantrone was given to 19 patients with liver metastases from breast cancer and biochemical evidence of liver dysfunction. In all, 2 patients received the drug at a dose of 10 mg/m2 on days 1 and 2 of the first course of treatment; 1 patient was given 9 mg/m2 and 17 received 8 mg/m2. Subsequent courses were given at a dose of 10 mg/m2. Three patients (16%) showed a partial response, with time to progression of between 3 and 7 months. Toxicity was considerable, with myelosuppression being the major problem.
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PMID:Phase II study of mitoxantrone for liver metastases from breast cancer. 259 Oct 4

Mitoxantrone, an anthracenedione, has been shown to be as effective as doxorubicin, but with less local or systemic toxicity, when used for the treatment of advanced breast cancer. As the high molecular weight and hydrophilic property of this drug let us predict a slow intracavity resorption, we tested its use in the treatment of malignant effusions refractory to systemic chemotherapy. 18 women, 43 to 83 years old, with cytologically demonstrated metastatic pleural effusions, and with prominent clinical symptoms, were included in the study. All these patients were refractory to hormonotherapy and combination chemotherapy (previous regimens included anthracyclines in 17 patients but none had received systemic mitoxantrone). No previous local treatment had been attempted. During the study period, no other treatment has been given. Mitoxantrone (6 mg/m2) has been administrated after effusion aspiration. A complete response was seen in 8 patients, a partial response in 5, and no change in the 5 others but one had received only one injection on account of a transitory shock immediately after. No others side effects were reported (fever, local pain, alopecia, vomiting). No patient had evidence of myelosuppression. These results suggest that intracavity injection of mitoxantrone is feasible and generally safe in most patients. Some efficiency has been seen in previously heavily treated patients refractory to systemic chemotherapy. Local administration of mitoxantrone deserves further investigation.
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PMID:[Efficacy and toxicity of intrapleural mitoxantrone: apropos of 18 cases of pleural metastases of breast cancer]. 266 79

To determine the safety and efficacy of mitoxantrone use in hyperbilirubinemic breast cancer patients, a prospectively determined dosage schedule was evaluated in a multi-center trial. Pretreatment bilirubin prospectively defined three groups: Controls (with normal bilirubin) and two Study groups (with either moderate or severe bilirubin increase). Bilirubin determined initial mitoxantrone dose as well: bilirubin less than 3.5 mg/dl, 14 mg/m2; and bilirubin greater than or equal to 3.5 mg/dl, 8 mg/m2. Mitoxantrone at 14 mg/m2 was well tolerated in patients with moderate hepatic dysfunction. Patients with severe hepatic dysfunction demonstrated a mixed toxicity picture, with performance status (ECOG level 3) defining a population with limiting myelosuppression and/or early death. The survival of Study patients with severe hepatic dysfunction (median 17 days) was significantly worse than both Control (p less than 0.01) and Study (p less than 0.05) patients with lower bilirubin. Entry performance status (ECOG level 0-2 versus level 3) profoundly influenced survival (median survival 222 days versus 25 days, respectively, p less than 0.0001). Objective responses were seen in patients with both normal and elevated bilirubin. Bilirubin reduction following mitoxantrone commonly occurred, representing at least an indicator of favorable prognosis. Recommendations for mitoxantrone use include: 1. Patients with moderate bilirubinemia tolerate 14 mg/m2 mitoxantrone with reasonable chance for benefit. 2. Patients with severe hepatic dysfunction and poor performance status should not be given mitoxantrone. A definitive recommendation regarding use of reduced 8 mg/m2 mitoxantrone in patients with severe hyperbilirubinemia and favorable performance status requires further study.
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PMID:Mitoxantrone use in breast cancer patients with elevated bilirubin. 269 28

Nineteen evaluable patients with advanced carcinoma of the vulva or vagina were treated with mitoxantrone, 12 mg/m2, every 3 weeks. All patients had good performance status and measurable disease and only nine had received prior chemotherapy. No complete or partial responses were noted. The major toxicity was myelosuppression; other toxicity was mild, and no cardiac toxicity or drug deaths occurred. The median progression-free interval was 1.3 months for patients with vulvar cancer and 1.6 months for patients with vaginal cancer. Median survival was 3.2 months for patients with vulvar cancer and 2.7 months for patients with vaginal cancer. Mitoxantrone displays no activity in patients with advanced carcinoma of the vulva or vagina.
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PMID:Mitoxantrone in the treatment of advanced vulvar and vaginal carcinoma. A gynecologic oncology group study. 270 4

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


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