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)

Ifosfamide and vinorelbine have demonstrated single-agent activity against advanced non-small cell lung cancer. The dose-limiting toxicity of each agent is myelosuppression. Several trials have studied this combination to determine its toxicity and efficacy in non-small cell lung cancer. We conducted a dose-escalation study of vinorelbine in a novel (daily x 3) schedule with ifosfamide and granulocyte colony-stimulating factor support to define the dose-limiting toxicities and maximum tolerated dose of vinorelbine in this combination. Other investigators have studied this combination in the phase II setting. In our phase I study involving 42 patients, the recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2, each given on 3 consecutive days, followed by granulocyte colony-stimulating factor. The overall response rate was 40%, with a median survival of 50 weeks. Myelosuppression proved to be dose limiting for this regimen, without other major toxicities. Other groups have studied the ifosfamide/vinorelbine combination, and studies adding cisplatin to this regimen have been conducted as well. Given the tolerable toxicity and encouraging response rates and 1-year survival rate seen with this regimen, further investigation of the ifosfamide/vinorelbine regimen has continued in a phase II Cancer and Leukemia Group B trial. Further study of the potential application of the combination as induction therapy for stage III disease is warranted.
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PMID:A review of ifosfamide and vinorelbine in advanced non-small cell carcinoma of the lung. 953 5

Ifosfamide is an active drug in the therapy of paediatric tumours such as rhabdomyosarcoma, Ewings' sarcoma, Wilms' tumour, neuroblastoma, germ cell tumours and lymphomas. Myelosuppression is the major toxicity along with haemorrhagic cystitis. The latter is largely prevented by the use of concomitant mesna.
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PMID:The role of ifosfamide in paediatric cancer. 967 60

Phase II studies have confirmed gemcitabine (GEMZAR) to be an active single agent in treating non-small-cell lung cancer (NSCLC), with response rates averaging 21%. Toxicity, including myelosuppression, is mild, making gemcitabine an attractive agent to consider in combination regimens. Most experience with gemcitabine in combination has been with cisplatin. Five phase II studies have been performed using different scheduling and dosage regimens. Response rates varied from 38% to 54% and median survival was 8.4-14.3 months. This combination was well tolerated and required minimal hospitalization. Haematological toxicity of short duration was dose limiting, with thrombocytopenia WHO grades 3/4 in 16-52% of patients and neutropenia in 36-58%. Nausea and vomiting occurred with cisplatin. Ifosfamide has been combined with gemcitabine in a phase I/II study. Based on phase I data, ifosfamide 1500 mg m(-2)day(-1) was chosen for the phase II study. The overall response rate was 32%. Toxicity was mild and was mainly related to short-lived myelosuppression. In summary, the favourable toxicity profile of single-agent gemcitabine enables its safe combination with other active agents in the treatment of NSCLC. The combination with cisplatin appears particularly encouraging, and a phase III study comparing this combination with standard chemotherapy regimens is planned. The combination of gemcitabine with radiotherapy is also under investigation.
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PMID:Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. 971 86

A phase II study was performed to assess the safety and efficacy of ifosfamide and mitoxantrone in recurrent and/or metastatic squamous cell carcinomas of the head and neck. Treatment consisted of ifosfamide 1500 mg/m2 in 1000 ml saline, infused over 60 min and mesna 20% of the total dose of ifosfamide in three doses for 3 days combined with mitoxantrone 12 mg/m2 given as a short infusion on day 1. Treatment courses were repeated every 4 weeks until a total of six cycles. Twenty-two patients entered this trial, 13 of whom had received chemo- and radiation therapy, and nine patients who underwent radiation therapy with or without prior surgery. We observed no objective response, with the exception of two patients who experienced minor response (reduction of tumor size of 25%). The dose-limiting toxicity was myelosuppression with grade 3/4 leukocytopenia in seven patients (32%) and grade 3/4 neutropenia in 15 (68%). Severe organ toxicity except alopecia (91%) was not observed. Ifosfamide combined with mitoxantrone does not improve the therapeutic armentarium in recurrent squamous cell carcinoma of the head and neck.
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PMID:Ifosfamide and mitoxantrone in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck. 1129 Aug 67

Ifosfamide is an alkylating agent with proven efficacy in the treatment of solid tumours and malignant lymphomas. Because it causes only mild to moderate myelosuppression, ifosfamide is often used in combination regimens with other agents. Ifosfamide has been mainly used in therapy of lymphoma as a component of salvage regimens, but high-dose ifosfamide is also effective in the mobilization of peripheral stem cells for treatment of patients with relapsed or refractory lymphoma with regimens containing autologous stem cell transplantation. Based on promising data with a new combination regimen containing idarubicin, etoposide and ifosfamide (IIVP-16) in patients with poor-risk non-Hodgkin's lymphoma, we have performed a phase II study using DIZE (dexamethasone 20 mg i.v. days 1-4, idarubicin 8 mg/m2 i.v. days 1 + 2, ifosfamide 1.0 g/m2 continuous infusion (c.i.) days 1-4, and etoposide 160 mg/m2 c.i. days 1-4) in patients with relapsed or refractory Hodgkin's and non-Hodgkin's lymphoma. In 43 evaluable patients, the response rate was 58%, including 11 complete remissions (CR) and 14 partial remissions (PR). The mean duration of response was 8 months (1-30). Myelosuppression was generally mild with mean duration of neutropenia < 1000/microL of 2.5 days (range 0-18) and thrombocytopenia < 25,000/microL of 1.5 days (0-17). Thus, DIZE is an effective and safe regimen for pretreated patients with aggressive lymphoma. These results appear to compare favourably with other salvage regimens such as IMVP-16 or DHAP. In conclusion, salvage regimens containing ifosfamide can play an important role in patients who are not eligible for high-dose chemotherapies. Moreover, ifosfamide might also have a role in reducing tumour burden and selecting those patients who qualify for HDCT.
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PMID:The role of ifosfamide in the treatment of relapsed and refractory lymphoma. 1148

To evaluate activity and toxicity of a non platinum-based triplet including Gemcitabine, Ifosfamide and Navelbine (GIN) in advanced NSCLC. Stage IIIB/IV NSCLC patients with WHO PS < 2 and bidimensionally measurable disease entered the study. Gemcitabine 1000 mg/sqm day 1 and 1000-800 mg/sqm day 4, Ifosfamide 3 g/sqm day 1 (with Mesna), Navelbine 25 mg/sqm day 1 and 25-20 mg/sqm day 4 were administered intravenously every 3 weeks. Objective responses (ORs) were evaluated every 2 courses: a maximum of 6 courses were administered in responding patients. According to Simon's optimal two-stage design more than 18 ORs out of 54 patients were required to establish the activity of this regimen. Fifty patients entered the study. Main characteristics of the 48 evaluated patients were: median age 63 years, ECOG performance status 0 = 65%, stage IV disease 79% and non-squamous histology 71%. The total number of courses administered was 200, median per patient 4 (range 1-6). Toxicities were evaluated according to WHO criteria: neutropenia grade 3-4 occurred in 47% of the courses; thrombocytopenia grade 3-4 in 6.6%; anaemia grade 3 in 3.5%. Twelve episodes of febrile neutropenia were reported and three patients required hospital admission. No toxic death was reported. Non-haematological toxicity, including skin rash, alopecia and fatigue, were generally. Twenty-five ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI: 37.4-66.5%). One-year survival was 46.5%. This non-platinum-based outpatient triplet showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose-limiting. The GIN regimen may represent a valuable alternative to standard platinum-based doublets and triplets in the treatment of advanced NSCLC and further studies with this platinum-free combination are warranted.
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PMID:Gemcitabine, Ifosfamide and Navelbine (GIN): activity and safety of a non-platinum-based triplet in advanced non-small-cell lung cancer (NSCLC). 1172 Apr 27

Docetaxel has shown activity in the treatment of non-small-cell lung cancer (NSCLC) that has failed previous chemotherapy. Ifosfamide is an active alkylating agent used in the first-line treatment of NSCLC. We conducted a phase II study of docetaxel and ifosfamide chemotherapy in two groups (one with and one without previous paclitaxel treatment) of NSCLC patients who had failed previous chemotherapy, to assess the response and toxicity of this combination chemotherapy. Fifty patients were enrolled from June 2000 to December 2001, including 26 patients treated with paclitaxel-containing agents and 24 patients who had never been treated with paclitaxel. Treatment consisted of docetaxel 60 mg/m(2) and ifosfamide 3 g/m(2) intravenous infusion on day 1 of every 3 weeks. Two hundred and thirty-eight cycles of treatment were given, with a median of 5 cycles (range, 1-8 cycles). All patients were evaluable for toxicity profile and response rate. The major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 40 patients (80%) during treatment. Febrile neutropenia occurred in 7 patients (14%). Grade 3 anemia occurred in 2 patients. The majority of patients needed a decrease in the treatment dose due to grade 4 or febrile neutropenia. Interstitial pneumonitis occurred in 3 patients, leading to the death of two. Other toxicities were few and mild in severity. After two cycles of treatment, 5 patients (10%) had a partial response (95% confidence interval 1.7-18.3%), including 2 patients previously treated with paclitaxel and 3 who had not received this treatment. More patients who had been previously treated with paclitaxel suffered from progressive disease than among those who had never been treated with paclitaxel (P = 0.049). The median time to disease progression was 5 months and the median survival was 8.2 months. Median survival was 7.6 and 8.7 months, respectively, in patients with and without previous paclitaxel treatment (P = 0.56). Median survival was 8.7 and 7.6 months in patients receiving docetaxel and ifosfamide as second- and third-line chemotherapy, respectively (P = 0.327). In conclusion, docetaxel and ifosfamide salvage chemotherapy produces a relatively low response rate, low dose intensity, and higher proportion of severe neutropenia in NSCLC. Physicians should be alert to the potential of interstitial pneumonitis. Nevertheless, median survival was of a reasonable duration.
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PMID:Phase II study of docetaxel and ifosfamide combination chemotherapy in non-small-cell lung cancer patients failing previous chemotherapy with or without paclitaxel. 1258 75

Ifosfamide is an alkylating agent with well-demonstrated efficacy against a large number of malignant diseases. With cyclophosphamide it shares a toxicity profile characterized by myelosuppression and urotoxicity, but ifosfamide has additionally disclosed adverse neurological effects. Ifosfamide-related central nervous system toxicity is characterized by metabolic encephalopathy of varying severity. Symptoms have been reported in 5-30% of all patients treated with ifosfamide. The mechanism of ifosfamide-related central nervous system toxicity has not been fully elucidated, although the symptoms have most often been noted when the drug is given at high doses or administered orally. The neurotoxicity is generally self-limiting and reversible between 48 and 72 h after discontinuation of ifosfamide, although fatal sequelae have been reported. Therapeutic options are now available.
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PMID:Neurological toxicity of ifosfamide. 1458 41

Purpose. To define the maximally tolerated dose (MTD) of ifosfamide when given with G-CSF on an every other week schedule, and to define the MTD of edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods. Forty-one patients with metastatic or unresectable, locally advanced sarcoma participated in this 2-step phase I trial.The starting dose of ifosfamide was 10 gm/m(2) given by continuous intravenous infusion over 4 days every 2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m(2) intravenously every 2 weeks was added in subsequent cohorts of patients.Results. Myelosuppression was the most prominent toxicity. Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide 12 gm/m(2) given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m(2) could be given safety as an intravenous bolus with ifosfamide 10 gm/m(2) every 2 weeks. Therapeutic responses were observed in patients with measurable disease.Conclusions. This study demonstrates the feasibility of administering a dose-intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be applied in the adjuvant or neo-adjuvant setting.
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PMID:Evaluation of dose-intense Ifosfamide, with and without edatrexate, in adults with sarcoma. 1852 Dec 74

Background. Pharmacokinetic data on clearance of ifosfamide in hemodialysis patients are limited. Consequently, these patients are excluded from therapy with this agent. We review the outcomes for patients at our institution with end stage renal disease on dialysis who received ifosfamide for metastatic sarcoma. Patients and Methods. We treated three patients with end stage renal disease on hemodialysis with escalating doses of ifosfamide. Data on radiographic response to therapy, WBC and platelet counts, signs or symptoms of infection, neuropathy and bladder toxicity are reported. Starting doses of ifosfamide were based on review of the literature available with subsequent modifications based on each patient's prior exposure to myelosuppressive agents and on symptoms of neurotoxicity and the degree of myelosuppression following each cycle of chemotherapy. Results. Myelosuppression was the most common side effect from therapy, but no patient developed a life threatening infection, neurotoxicity, or hematuria. One patient developed epistaxis in the setting of thrombocytopenia while on warfarin therapy. All patients had clinical evidence for therapeutic response and two had documented radiographic improvement following ifosfamide administration. Conclusion. Ifosfamide can be used safely in combination with hemodialysis in patients with end stage renal disease.
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PMID:Ifosfamide may be safely used in patients with end stage renal disease on hemodialysis. 2010 95


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