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)

One hundred and three patients previously treated with chemotherapy including an anthracycline were entered in a VMMC protocol study: vindesine (Eldisine), mitoxantrone (Novantrone) and mitomycin C (Ametycine). Group A consisted of 41 women who received the protocol published by Belpomme: vindesine (2.5 mg/m2 day 1 and 8) and mitoxantrone (12 mg/m2/day) every 4 weeks, and mitomycin C (8 mg/m2) every 8 weeks. Group B consisted of 62 patients who were treated with a modified protocol: vindesine (2.5 mg/m2) and mitoxantrone (12 mg/m2) every 3 weeks on day 1, and mitomycin C (8 mg/m2) every 6 weeks. Tolerance was acceptable with 79% of patients complaining of weakness. There was a 66% incidence of gastro-intestinal toxicity, a 10.7%-incidence of neurotoxicity (reversible dysethesias), and a 5.8% incidence of cardiotoxicity. There was considerable hematotoxicity of grade 2, 3 and 4: neutropenia 16.6%, thrombocytopenia 7.7%, anemia 21.4%. There was a 19.2% overall objective response rate (CR and PR) (95% confidence interval: 12-30) (CR: 3.2%). The median duration of the response was 39 weeks. There was no significant difference in response rates whether or not the patients (19 cases) were undergoing simultaneous hormonal therapy and no difference according to the protocol used. Similarly, neither menopause nor a previous response to anthracyclines had any effect on the response rate. The 19.2% response in this protocol is similar to other breast cancer salvage chemotherapy protocols for patients who have failed to respond to anthracyclines (< 20%).
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PMID:[A study of VMMC protocol (vindesine, mitoxantrone, mitomycin C) as a salvage chemotherapy in advanced breast cancers]. 139 55

The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.
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PMID:Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity. 191 86

Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM-CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty-three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM-CSF. The following side effects were associated with the administration of rhGM-CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response.
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PMID:Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study. 219 41

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

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

No published data are available concerning the activity and tolerability of intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in humans. To fill this gap, 19 patients with advanced ovarian cancer previously treated with at least one first-line chemotherapy cycle received the following myelosuppressive regimen: mitoxantrone (DHAD) 12 mg m-2 i.v. on day 1; ifosfamide (IFO) 4 g m-2 i.v. on days 1 and 2; mesna 800 mg m-2 i.v. t.i.d. on days 1 and 2. G-CSF (Filgrastim) was given at a dose of 5 micrograms/kg/day i.m. from day 6 to day 19, its pharmacokinetics being assessed in five patients. The neutrophil nadir was observed after a mean period of 8 days, and the neutrophil count was < 1.0 x 10(3) mm-3 for a mean of 6 days during the cycle of chemotherapy. The neutrophil count fell after the withdrawal of G-CSF on the 19th day of treatment. The difference in absolute neutrophil count between day 19 and day 21 was statistically significant (P = 0.0001); nevertheless, at day 21 no WHO grade 3-4 neutropenia was reported. DHAD and IFO were respectively given at 95% and 93% of the planned dose. The pharmacokinetics of G-CSF i.m. seems to be similar to that of the drug given subcutaneously. No evidence of cumulative myelosuppression was observed. G-CSF was well tolerated and no complications were observed at the injection sites. In conclusion, if the results obtained in this pilot study regarding the activity of i.m. G-CSF are confirmed by a randomised trial, the intramuscular administration of G-CSF could become a valid alternative for patients who dislike the subcutaneous route and who are being treated with chemotherapy that does not induce profound thrombocytopenia.
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PMID:The intramuscular administration of granulocyte colony-stimulating factor as an adjunct to chemotherapy in pretreated ovarian cancer patients: an Italian Trials in Medical Oncology (ITMO) Group pilot study. 751 30

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.
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PMID:A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma. 795 Sep 23

Malignant pleural effusion due to metastatic sarcoma is a difficult problem to treat. Mitoxantrone hydrochloride is an anthracenodione that has been reported to be useful when used intracavitary for malignant effusion due to gynaecological malignancies. We reviewed 15 cases of malignant pleural effusion due to pleural involvement by metastatic sarcoma that were treated with intrapleural mitoxantrone. None of the patients had previous pleurodesis. A standard dose of 20 mg per square metre in 50 cc of saline solution was instilled by chest tube after drainage of the effusion. All patients were initially evaluated by chest CAT scans and chest films, control films were done immediately and 6 weeks after treatment. Thirteen cases were evaluated. Three patients presented with fever, two patients had local pain and one patient developed neutropenia. Three patients did not respond to the treatment. Complete resolution of the effusion was achieved in 76% of the patients: such an effect could be due to the local antineoplastic activity of the drug. We believe that mitoxantrone is effective in the treatment of malignant pleural effusion due to pleural involvement with sarcoma without causing significant local or systemic toxicity.
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PMID:Mitoxantrone for malignant pleural effusion due to metastatic sarcoma. 830 71


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