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 (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione dihydrochloride) in animal studies appears to have a mechanism of action and broad antitumor spectrum similar to the anthracyclines and in preliminary animal studies is without cardiotoxicity. To determine the maximally tolerated dose, mitoxantrone was given to 25 patients with various advanced solid tumors. Sixteen patients had received prior doxorubicin and/or lomustine (CCNU). Myelosuppression was the major toxic effect. All 13 patients who received mitoxantrone doses greater than or equal to 2.73 mg/m2 x 5 days experienced moderate (2000--3000 cells/mm3) or severe (less than 2000 cells/mm3) leukopenia. Thrombocytopenia was also encountered in three of these 13 patients (severe in one, less than 50,000 cells/mm3). At dose levels less than 2.73 mg/m2 x 5 days, myelosuppression was seen in four of 12 patients (three with mild leukopenia and one with mild thrombocytopenia). The blood cell count nadir occurred at 10 days and full recovery occurred by Day 21. Minor clinically insignificant ECG changes occurred in five patients. Minor and transient antitumor effects were seen in five patients. The maximum tolerated dose of mitoxantrone over a 5-day course is 2.73 mg/m2, with leukopenia being the limiting toxic effect.
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PMID:Phase I study of a 5-day schedule of mitoxantrone (dihydroxyanthracenedione). 708 34

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

Cyclic intra-arterial infusion chemotherapy using Mitoxantrone via reservoir system was prescribed for 8 patients with advanced hepatocellular carcinoma. According to the clinical staging system, two patients were in Stage III and the other six patients in Stage IV-A. Vp-3 portal invasion was observed in six out of the eight patients. Mitoxantrone (5-8 mg/body) was administered intra-arterially via port-a-cath device every 4 weeks. For tumor response, there were two PR cases, four NC cases, and two PD cases. Thus, the response rate was 25%. The mean survival period was 6.5 months, and 1-year survival rate was 13%. In one of two PR cases, the survival time has been more than two years so far. Gastrointestinal toxicities such as nausea and vomiting were not severe. Critical myelosuppression requiring medication was not observed. Although a temporary increase of serum bilirubin was found in two cases, no severe damage to hepatic function was observed. From our preliminary data, this arterial infusion chemotherapy using Mitoxantrone via reservoir system can be safely performed on non-hospitalized patients with advanced hepatocellular carcinoma, and may be a useful treatment modality.
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PMID:[Clinical study of cyclic intra-arterial chemotherapy using mitoxantrone for advanced hepatocellular carcinoma]. 808 50

Fifty-eight evaluable patients with acute leukemia were treated with Mitoxantrone (DHAD) according to two schedules: 14 mg/M2 as a single I.V. pulse dose administered three-week intervals, and 4 mg/M2/day for five days every three weeks. Six of 58 patients achieved a complete remission. One complete remission and 1 partial remission were observed among 26 patients treated with the single pulse schedule. Five (16%) complete remissions were attained among 32 patients treated on the daily x 5 schedule. Responses were observed only in patients with non-lymphoblastic leukemia. DHAD was very well tolerated with myelosuppression as the major toxicity. Nausea and vomiting were minimal. Subclinical cardiac toxicity occurred in two patients. This was identified by serial reductions in cardiac ejection fractions. DHAD appears to have significant activity in acute non-lymphoblastic leukemia with minimal toxicity.
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PMID:Mitoxantrone (dihydroxyanthracenedione) in acute leukemia. An evaluation of two treatment schedules by the Southwest Oncology Group. 826 31

The intratumoral (i.t.) delivery of anticancer drugs aims at controlling tumor growth and thereby provides palliative treatment for liver neoplasms. Mitoxantrone is a good candidate for local or regional administration because (1) its metabolism is mainly hepatic, (2) it has a steep dose-response curve for multiple solid tumors, and (3) its fixation in tissues is sustained without vesicant effects after extravasation. We compared the tolerance, pharmacokinetics, and antitumor effects of mitoxantrone on hepatic VX2 tumors in rabbits treated with i.t. intraarterial hepatic (i.a.h.) or i.v. mitoxantrone, i.t. ethanol; or i.t. 0.9% NaCl and in control animals. Tumor growth rates (TGRs) were evaluated at 9 days after treatment. Myelosuppression was the limiting toxicity of i.v. mitoxantrone at 1.5 mg/kg (maximal tolerated dose, MTD), but neither i.t. nor i.a.h. administration led to hematologic toxicity at the same dose. The mitoxantrone retained in tumors after i.t. administration was seen as blue-stained areas of complete necrosis according to histologic analysis. Pharmacokinetic parameters showed a significantly decreased systemic exposure to the drug after both regional treatments, although the i.a.h. route appeared to have an edge over the i.t. route. TGRs were significantly reduced after i.t. mitoxantrone (81 +/- 62%), i.a.h. mitoxantrone (337 +/- 110%), and i.t. ethanol treatments (287 +/- 117%) as compared with control values (886 +/- 223%; p < 0.01). Treatment with i.v. mitoxantrone (816 +/- 132%) had no antitumor effect, nor did NaCl injections (868 +/- 116%). Mitoxantrone given i.t. induced the highest antitumor effects, resulting in a 3.5-fold reduction in TGRs as compared with i.a.h. mitoxantrone and i.t. ethanol treatments (p < 0.02). Treatment with i.t. mitoxantrone provided efficient antitumor therapy without producing major side effects. This method should be considered as palliative treatment for nonresectable liver tumors and other localized malignancies.
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PMID:Pharmacokinetics and antitumor effects of mitoxantrone after intratumoral or intraarterial hepatic administration in rabbits. 854 84

Twenty-three patients with acute non lymphocytic leukemia (ANLL), were treated with a single-6 day course of Mitoxantrone 6mg/m2/day, Etoposide 80mg/m2/day and intermediate dose Cytarabine (ara-C) 1g/m2/day (MEC). Patients who achieved complete remission (CR) were submitted to a 4-day-course of MEC as consolidation. Seventeen patients (73.9%) obtained CR, five patients (22.7%) were resistant to the treatment and one patient died during induction. Median remission duration was 11 months; overall median survival was 16 months. Relapses occurred in 11 patients; eight patients are still alive: 6 in 1st, 2 in 2nd CR (mean survival 20.1 months, range 17-26). All patients experienced severe myelosuppression comparable to that observed after classical induction cycles including ara-C in continuous intravenous infusion; none, however, died of infection. Non-hematologic toxicity was minimal; in particular, neurotoxicity was not observed. According to our results, the MEC regimen, which was previously demonstrated to be active in refractory patients, represents an effective induction treatment in ANLL, with an acceptable toxicity.
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PMID:MEC (mitoxantrone, etoposide and intermediate dose cytarabine): an effective induction regimen for previously untreated acute non-lymphocytic leukemia. 859 Aug 45

Fifty-five consecutive patients with metastatic breast cancer (MBC) (n = 57) were treated with a combination of levofolinic acid (I-FA) 100 mg/m2 plus 5-fluorouracil (5-FU) 340 mg/m2 i.v. on day 1-3, cyclophosphamide (CTX) 600 mg/m2 i.v. on day 1 and mitoxantrone (DHAD) 12 mg/m2 i.v. on day 1. DHAD dose was progressively escalated by 2 mg/m2/cycle up to 18 mg/m2 in the absence of dose-limiting toxicities. Granulocyte colony stimulating factor (G-CSF) was given s.c. in order to prevent neutropenia. DHAD dosage could be increased to 18 mg/m2 in 66 out of 317 cycles of chemotherapy (21%). In most patients the dose-limiting toxicity was represented by myelosuppression. A statistically significant correlation was found between median white blood cell (WBC) or absolute neutrophil count (ANC) nadir and DHAD dose level. Moreover, a statistically significant correlation was observed between the number of chemotherapeutic cycles, nadir ANC and WBC, and the occurrence of anemia and thrombocytopenia of increasing severity. These data suggest the occurrence of progressive cumulative bone marrow toxicity. Although patients who reached different DHAD levels showed differences in mean dose intensity, such differences were not statistically significant. No correlation was found between the increase in dose intensity and type, rate or duration of objective responses. In patients with metastatic breast cancer the overall response rate was 72% (95% CL 57-84%) with a 18% complete response rate. Median duration of response was 12 and 11 months, respectively, for complete and partial responses. Projected median survival of the whole series of patients with MBC was 18 months. These data demonstrate that the combination of 5-FU with I-FA, CTX and DHAD is very active against MBC. G-CSF use allows the increase DHAD dosage up to 18 mg/m2/cycle, but its use may be linked to the occurrence of sometimes severe cumulative hematological toxicity.
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PMID:Dose intensification of mitoxantrone in combination with levofolinic acid, fluorouracil, cyclophosphamide and granulocyte colony stimulating factor support in advanced untreated breast cancer patients. A multicentric phase II study of the Southern Italy Oncology Group. 909 30

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.
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PMID:[Lipiodol with and without Gelfoam in primary liver tumors. Plasma levels of Mitoxantrone and clinical results]. 929

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.
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PMID:A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors. 974 May 42

Anthracyclines are among the most active agents in metastatic breast cancer. Mitoxantrone demonstrated a different toxicity profile when compared to doxorubicin. We performed a phase I/II study of single-agent high-dose mitoxantrone therapy for advanced breast cancer. Nineteen patients who had a diagnosis of metastatic breast cancer received treatment at the M.D. Anderson Cancer Center between June 1986 and December 1987. The patients received escalating doses of mitoxantrone until a maximum tolerated dose (MTD), defined as grade 3 or 4 nonhematologic toxicity or infection, was obtained. The starting dose of 25 mg/m2, given by short intravenous infusion, was escalated by 25% in each five-patient cohort if each patient in the previous cohort tolerated the initial course and 2 or fewer patients reached the MTD. The median cumulative dose of mitoxantrone was 93 mg/m2 (range, 25-205) and the maximum single dose was 39 mg/m2. Myelosuppression was the dose limiting toxicity. The median duration of granulocyte count < or = 250/microl was 5-7 days. Four patients (22%) had infections that required hospitalization, 3 patients (17%) had cardiac toxicity. One patient (6%) achieved a complete response, and 3 (17%) had a partial response, with an overall response rate of 22.3%. No apparent dose-response relationship was observed in our study. The mitoxantrone dosage recommended for phase II studies is 25 mg/m2 every 3-4 weeks. We conclude that high-dose mitoxantrone therapy for metastatic breast cancer was relatively well tolerated but was not associated with a higher response rate than that of standard dose mitoxantrone.
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PMID:Phase I/II trial of high dose mitoxantrone in metastatic breast cancer: the M.D. Anderson Cancer Center experience. 1044 21


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