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)

A total of 64 courses of ifosfamide (IFM) treatments for sarcoma patients were evaluated for toxic effects. A dose of 100 ml of 1/2 diluted Maalox by normal saline was instilled into urinary bladder with clump of catheter for 15 min for uroprotection instead of Mesna that was not available in Japan at that time. Forty-six courses of ifosfamide treatment in 12-16 g/m2 doses with daily Maalox instillation resulted only one hemorrhagic cystitis, while 18 courses at a dose of 6-10 g/m2 of IFM without Maalox eventuated in 5 cases of hemorrhagic cystitis. Forty-six courses of ifosfamide treatment at a dose of 12-16 g/m2 (mean dose of 14.4 g/m2) for 5 to 6 day continuous infusion were evaluated also for myelosuppression, nephrotoxicity, neurotoxicity, and other toxicities. Myelosuppression was acceptable, although the absolute neutrophil count of the 80% course was below 500. No patient showed neurotoxicity characterized by confusion or somnolence. No course resulted in abnormal serum creatinine elevation, although two of 46 courses caused an abnormal decrease of creatinine clearance. One patient had arrhythmia that required medical treatment after 5 courses of IFM treatment.
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PMID:[Toxic effects of ifosfamide in the treatment of bone and soft tissue sarcomas]. 845 88

Ifosfamide (5 g/m2) was compared with its parent analogue cyclophosphamide (1.5 g/m2) in a randomized phase II study. Both drugs were given by 24-h intravenous (i.v.) infusion every 3 weeks along with i.v. bolus infusions of mesna (400 mg/m2), which was given every 4 h for nine administrations. Eligibility criteria included an age of 15-75 years, biopsy-proven advanced metastatic soft-tissue sarcoma, and a World Health Organization performance status of 0-2. Exclusion criteria were prior treatment with classic alkylating agents, a creatinine level of > 150 mumol/l, a bilirubin level of > 20 mumol/l, a leukocyte cell count of < 3.5 x 10(9)/l, and a platelet count of < 100 x 10(9)/l. A total of 171 patients were entered, 24 of whom were ineligible and 12, inevaluable, leaving 135 patients evaluable. In all, 67 patients were treated with cyclophosphamide, and the overall response rate was 7.5%. All responders to cyclophosphamide were patients who had not received prior chemotherapy (13% of 38 patients). Another 68 patients were given ifosfamide, 18% of whom responded to treatment. Of the 28 ifosfamide-treated patients who had received prior chemotherapy, 7% were responders. The response rate for the remaining 40 patients was 25%. The higher overall response rate (P = 0.13) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy.
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PMID:Cyclophosphamide versus ifosfamide: a randomized phase II trial in adult soft-tissue sarcomas. The European Organization for Research and Treatment of Cancer [EORTC], Soft Tissue and Bone Sarcoma Group. 845 94

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m2 followed by a 24-h infusion of ifosfamide at 5 g/m2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses. The median time to progression was 29 weeks for all evaluable patients and 67, 40, and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (World Health Organization grades 3 and 4) in 73% of the evaluable patients. Other side effects were rare and usually well manageable.
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PMID:Ifosfamide plus doxorubicin in previously untreated patients with advanced soft-tissue sarcoma. 845 99

The Southwest Oncology Group (SWOG) performed a phase II trial of a combination of ifosfamide/mesna/cisplatin in patients with metastatic soft-tissue sarcoma who had previously received one chemotherapeutic regimen. A total of 39 patients were registered in the study, including 7 treated during a limited-institution pilot phase; 38 patients were fully eligible and evaluable. During the pilot phase, patients were treated with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on days 2 and 9. Due to excessive myelosuppression, the day-9 cisplatin dose was dropped when the study was opened groupwide, and the subsequent 32 patients were treated at 3- to 4-week intervals with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on day 2. Myelosuppression was severe, with granulocytopenia (< 0.5 x 10(9)/l) being observed in 26 of 38 patients. Three cases of National Cancer Institute grade 3 or 4 nephrotoxicity (serum creatinine, > 3 times the normal value) and three cases of grade 3 or 4 central nervous system toxicity were reported. Overall, three complete and five partial responses were achieved, for a major response rate of 21%. The median survival of all patients was 11 months. We conclude that ifosfamide-based chemotherapy can produce objective responses in previously treated patients with metastatic soft-tissue sarcoma but that cisplatin increases the toxicity of therapy. Phase II trials of new agents are needed to identify drugs with clinical activity in the treatment of soft-tissue sarcomas.
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PMID:Phase II trial of ifosfamide and cisplatin in the treatment of metastatic sarcomas: a Southwest Oncology Group study. 845 1

Currently, anthracyclines and ifosfamide are the most effective drugs for the treatment of disseminated soft-tissue sarcoma. We designed a treatment protocol of rapidly alternating epirubicin/dacarbazine and ifosfamide for previously untreated soft-tissue sarcoma, whereby 100 mg/m2 epirubicin was given on day 1, 500 mg/m2 dacarbazine was given on days 1 and 2, and 6,000 mg/m2 ifosfamide given via 24-h infusion was begun on day 15. The entire treatment cycle was scheduled to begin again on day 28 if the leukocyte count had reached 3.0 x 10(9)/l. From June 1988 to May 1991, a total of 28 patients were enrolled in the study. Eight patients (31%) achieved a partial response to therapy. The median duration of partial response was 8.5 months, and the median time to progression for all patients was 5 months. Myelosuppression was dose-limiting (leukocyte nadir, 1.7 x 10(9)/l; platelet nadir, 70 x 10(9)/l). Prolonged myelosuppression forced frequent therapy delays; therefore, only 74% of the planned doses could be given. The nonhematologic toxicity was tolerable. This rapidly alternating treatment protocol was determined to offer no therapeutic advantage over anthracycline therapy either alone or in combination with dacarbazine in terms of response rate or time to disease progression. The inclusion of hematopoietic growth factors, however, might ameliorate the dose-limiting myelosuppression and permit the administration of higher doses.
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PMID:A pilot study of rapidly alternating epirubicin/dacarbazine and ifosfamide as first-line therapy for metastatic soft-tissue sarcoma in adults. 845 2

On the basis of ifosfamide's demonstrated single-agent activity in adult soft-tissue sarcoma, the Eastern Cooperative Oncology Group (ECOG) tested whether ifosfamide would add to the efficacy of doxorubicin in a three-regimen, controlled phase III trial. Doxorubicin, ECOG's standard to which newer chemotherapeutic treatments are compared, was given at a dose of 80 mg/m2 every 3 weeks and was designated the control regimen. Ifosfamide was given at a dose of 3,750 mg/m2 on days 1 and 2 every 3 weeks in combination with 30 mg/m2 doxorubicin given each day for 2 days; additionally, mesna was given to counter the genitourinary toxicity associated with ifosfamide. A second experimental regimen consisted of doxorubicin (40 mg/m2), mitomycin (8 mg/m2), and cisplatin (60 mg/m2), all given intravenously on day 1, with repeated cycles being scheduled for day 21. Of the 279 adults with soft-tissue sarcoma who were entered in the study, 260 were analyzed. The overall response rate was 20% for doxorubicin, 34% for ifosfamide/doxorubicin, and 31% for doxorubicin/mitomycin/cisplatin, with the difference between the first two regimens being significant (P = 0.04). The median survival was 8.8, 11.5, and 9 months, respectively, for the three regimens. Myelosuppression, the predominant toxicity, occurred in 60%, 88%, and 58% of patients, respectively.
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PMID:Efficacy of ifosfamide in combination with doxorubicin for the treatment of metastatic soft-tissue sarcoma. The Eastern Cooperative Oncology Group. 845 6

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.
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PMID:The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group. 845 7

Thirty patients with previously untreated and measurable or evaluable advanced soft tissue sarcoma entered this phase II study. Median age was 53 years (range: 24-71 years). Starting dose of Epirubicin was 100 mg/m2 IV bolus on day 1 combined with Ifosfamide, 2.5 g/m2, as a 6-hr IV infusion on day 1 and day 2 with uroprotection with Uromitexan, 1.6 g/m2, on day 1 and day 2. This schedule was repeated every 3 weeks. In case of minimal myelosuppression, the dose of Epirubicin was increased by 10 mg/m2 up to 130 mg/m2. Ifosfamide dosage was not increased. Mean cumulative dose of Epirubicin received was 477 +/- 272 mg/m2 (range: 200-1200 mg/m2). Of 27 evaluable patients (WHO criteria), 13 had a partial response (48%), 4 showed no change (15%), and 10 had progressive disease (37%). Median time to progression was 27 weeks. Of 27 patients evaluable for toxicity, hematological toxicity at day 21 was mild. Nonhematological toxicities consisted of nausea and vomiting in 82% of patients (WHO grade 3-4 = 19%), stomatitis in 44.5% (WHO grade 3 = 7.5%), and alopecia in 96% (WHO grade 2-3 = 89%). Appearance of cardiac dysfunction without heart failure during the treatment led to discontinuation of this chemotherapy in 3 patients. The results of this study show that the combination of Epirubicin and Ifosfamide is effective in advanced soft tissue sarcoma with an acceptable toxicity. However, we cannot conclude from this trial whether combination Epirubicin and Ifosfamide is superior to Epirubicin alone.
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PMID:Epirubicin and ifosfamide in advanced soft tissue sarcoma: a phase II study. 846 14

Tumor size is a significant prognostic variable for attaining complete regression (CR) with local hyperthermia (HT) and radiation therapy (RT). The addition of weekly chemotherapy was evaluated to improve the efficacy of thermoradiotherapy in poor-prognosis lesions (i.e. > or = 7 cm2 or > or = 14 cm3) which have an expected CR rate of approximately 30 +/- 8%. Patients were entered into a two-arm phase-II study: arm 1 = breast cancer (10 patients), ifosfamide (1.5 g/m2) + epirubicin (20 mg/m2) + HT + RT; arm 2 = sarcoma (7 patients) and head and neck cancer (9 patients), cisplatin (40 mg/m2) + HT + RT. Therapy encompassing 106 triple-modality sessions was generally well tolerated for both arms; 2 instances of grade-3 and 1 of grade-4 (arm 2) local toxicity (WHO criteria) were observed. There were 4 instances of grade-3 myelosuppression (arm 1). The CR rates for arms 1 and 2 were 70 and 19%, respectively, suggesting that the combination of ifosfamide/epirubicin/HT/RT deserves further investigation in the context of localized breast cancer.
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PMID:Local hyperthermia, radiation, and chemotherapy in locally advanced malignancies. 864 24

CC-1065 is a unique alkylating agent that preferentially binds in the minor groove of double-stranded DNA at adenine-thymine-rich sites. Although it has broad antitumor activity in preclinical models its development was discontinued because of deaths observed during preclinical toxicology studies. Adozelesin is a potent synthetic analog that was chosen for clinical development because it had a similar preclinical antitumor spectrum, but did not produce deaths similar to CC-1065 at therapeutic doses. Phase I evaluations using a variety of Adozelesin treatment schedules have been conducted. This report describes our experience using a multiple dose treatment schedule. Endpoints including antitumor response, maximum tolerated dose, dose limiting toxicity as well as other toxicities and the recommended Phase II starting dose were determined. Adozelesin was given as a 10 minute IV infusion for 5 consecutive days every 21 days or upon recovery from toxicity. The dose range evaluated was 6-30 mcg/m2/day. All patients had refractory solid tumors and had received prior cytotoxic treatment. Thirty-three patients (22 men: 11 women) were entered onto the study and 87 courses were initiated. Dose limiting toxicity was cumulative myelosuppression (leucopenia, thrombocytopenia). The maximum tolerated dose was 30 mcg/m2/day. The only other significant toxicity was an anaphylactoid syndrome that occurred in 2 patients. A partial response was observed in a patient with refractory soft tissue sarcoma. The recommended Phase II starting dose of Adozelesin using a 10 minute IV infusion for 5 consecutive days is 25 mcg/m2/day to be repeated every 4-6 weeks to allow recovery from myelotoxicity, based on our experience. Additional Phase I and II studies with Adozelesin are recommended.
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PMID:Phase I trial of Adozelesin using the treatment schedule of daily x5 every 3 weeks. 882 50


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