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)

We conducted a phase II study of ifosfamide and etoposide chemotherapy in patients with untreated extensive-disease small-cell lung cancer to assess response and toxicity. Between January 1994 and December 1995, 16 patients were treated. Ifosfamide and etoposide doses were ifosfamide 2 g/m2, with mesna, i.v. infusion over 30 minutes on days 1-3 and etoposide 80 mg/m2 i.v. over 120 minutes on days 1-3 every 4 weeks for up to six cycles. All patients were evaluable for toxicity profile and treatment response. As expected, the major toxicity was myelosuppression. With one exception, grade 3 or 4 leukopenia occurred in all patients during treatment, and 48.7% of the total courses had grade 3 or 4 leukopenia. Nine of 16 patients (56.3%) experienced episodes of febrile neutropenia. One toxic death due to febrile neutropenia with sepsis was documented. Toxicities other than leukopenia were few and mild in severity. After two cycles of treatment, the overall response rate was 81.3% (95% confidence interval 62.2-100) in this study. The median duration of response was 8 months and median survival was 11 months. In conclusion, ifosfamide and etoposide is an active combination regimen with acceptable toxicity profile in Chinese patients with extensive-disease small-cell lung cancer.
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PMID:Phase II study of ifosfamide and etoposide chemotherapy for extensive-disease small-cell lung cancer. 915 94

Ifosfamide is an analogue of cyclophosphamide active in the treatment of numerous tumours. Although its use by continuous infusion seems to be responsible for less toxicity, differences of efficacy and toxicity, observed according to its doses and schedules of administration, still remain debated. The objective of this study was to assess the toxicity of high-dose ifosfamide given by continuous infusion over 6 days and its therapeutic activity in various advanced tumours. Twenty-six patients were treated with 14 g/m2 ifosfamide, an equal dose of MESNA, and routine granulocyte- or granulocyte/macrophage-colony-stimulating factor during the intercycle. Courses were repeated every 3 weeks until disease progression or unacceptable toxicity occurred; 75 cycles were administered. The mean number of cycles per patient was 3 (range 1-11). Extrahaematological toxicity was manageable in most patients, WHO grade II or more neurological (5 patients) and renal (5 patients) toxicities occurring in those heavily pretreated with platinum compounds and presenting peritoneal disease. WHO grade III or more neutropenia occurred in 60% of cycles, while grade III-IV thrombocytopenia and anaemia were observed in 19% of them. Three partial responses (germ-cell tumour, chondrosarcoma, soft-tissue sarcoma) and one complete response (metastatic osteosarcoma) were assessed, all in patients with tumours refractory or resistant to standard-dose ifosfamide, which underlines the possibility of circumventing the resistance to ifosfamide given in conventional schedules. The present results confirm previous reports of changes in the therapeutic index of ifosfamide according to its dose and administration schedule.
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PMID:6-Day continuous infusion of high-dose ifosfamide with bone marrow growth factors in advanced refractory malignancies. 917 96

Hematological and clinical data of 14 children with neuroblastoma treated according to the German neuroblastoma therapy study NB 90 were analyzed. Therapy included 4 or 8 intensive therapy elements N1 (Etoposide 125 mg/m2 day 1-4, Vindesine 3 mg/m2 day 1, Cisplatin 40 mg/m2 day 1-4) and N2 (Vincristine 1.5 mg/m2 day 1 + 8, Dacarbazine 200 mg/m2 day 1-5, Ifosfamide 1500 mg/ m2 day 1-5, Doxorubicin 30 mg/m2 day 6 + 7) in alternating order. The hematological recovery was studied after 86 therapy elements N1/N2. G-CSF had been given in 23 therapy courses, while no cytokine was administered in 63 therapy courses. Mobilization of CD34+ cells was studied in 13 therapy courses with G-CSF. Severe myelosuppression with an absolute neutrophil count < 500/microL was noted 2-4 weeks after each therapy element. The use of G-CSF did not prevent, but shortened neutropenia. There was no difference in the number of infections nor time delay of therapy between the courses with or without G-CSF. In 11 therapy courses G-CSF was started on the day following the last chemotherapy dose (N1: day 5; N2: day 9). In 12 therapy courses G-CSF was given delayed, starting day 12 after the initiation of therapy. Kinetics of granulocyte recovery was similar in the early or delayed application of G-CSF. Neutrophil recovery after the therapy element N1 was earlier and faster compared to that of therapy element N2. The more rapid rise of the neutrophils after the N1 element was accompanied by an effective mobilization of CD34+ cells. Taking into account the limitations of this retrospective study, the data may help to optimize the application of G-CSF in a very intensive therapy study like NB90.
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PMID:[Kinetics of myelopoietic regeneration and mobilization of CD34-positive cells within the scope of the NB90 Neuroblastoma Therapy Study]. 934 Apr 28

The purpose of the study was to establish the maximum tolerated dose of ifosfamide, administered over 72 hr, in metastatic breast cancer patients, pretreated with chemotherapy. Ifosfamide and mesna were given at the same dose, in the same solution, using a portable Pharmacia CADD-1 pump connected to a central venous access, at three dose levels: 7.5 g/m2 (6 patients), 9 g/m2 (8 patients), 10.5 g/m2 (3 patients); the courses were repeated every 3 weeks. Seventeen patients with a median age of 55 years (range, 34-68) and median performance status of 0 (range, 0-2) were treated. The patients were pretreated with a median of 2 (range, 1-3) prior regimens including anthracyclines in 14 patients and paclitaxel in 9. Dose-limiting toxicity was defined as the occurrence of any of the following events in > or = 2/6 patients: absolute neutrophil count < 500/ml for > 7 days or < 100/ml for > 3 days; febrile neutropenia; grade 4 thrombocytopenia; any grade > or = 3 nonhematologic toxicity. The dose-limiting toxicities were febrile neutropenia and grade 4 thrombocytopenia in 2/3 patients treated at 10.5 g/m2. Seven patients achieved an objective response (response rate 41%; 95% CI, 18% to 67%). We conclude that 72-hr infusion of ifosfamide is feasible in ambulatory patients. The recommended dose for phase II studies is 9 g/m2, with courses repeated every 21 days.
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PMID:A dose-finding study of ifosfamide by three-day continuous infusion in pretreated, advanced breast cancer patients. 942 16

Ifosfamide, Carboplatin and Etoposide (ICE) therapy was used to treat 4 patients, 2 with refractory osteosarcoma, and one each with relapsed brain tumor and newly diagnosed brain tumor. ICE therapy was administered in doses of Ifosfamide 1,800 mg/m2 x 5, Carboplatin 400 mg/m2 x 2 and Etoposide 100 mg/m2 x 5. A total of 30 courses were administered. Two cases of osteosarcoma had a stable disease (range, 3-9 months) and 2 cases of brain tumor had a complete response by magnetic resonance imaging. Moderate or severe toxicity evaluated on a per course basis included: neutropenia 83%, thrombocytopenia 93%, fever 30%, hepatotoxicity 3%, and hemorrhagic cystitis 3%. The median time to hematologic recovery was 20 days. ICE therapy is highly effective for the treatment of refractory or recurrent solid tumors with acceptable toxicity.
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PMID:[Pilot study of relapsed osteosarcoma and brain tumor with ifosfamide, carboplatin and etoposide (ICE therapy)]. 949 32

Ifosfamide and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are among the most active agents for the treatment of non-small cell lung cancer, with single-agent response rates of 20% or greater in previously untreated patients with advanced disease. These two agents have been evaluated in several phase I and II trials of two-, three-, and four-drug regimens to determine their safety and efficacy in this patient population. Ifosfamide and paclitaxel doublets were evaluated in two phase I and II trials. Response rates ranged from 15.4% to 34%, with 1-year survival rates as high as 37%. Toxicity was acceptable, with greater degrees of myelosuppression seen with 24-hour infusion times for paclitaxel. Three-drug studies of ifosfamide, paclitaxel, and a platinum analogue have shown that these three drugs may be combined. Myelosuppression is considerable, however, and febrile neutropenia rates are high, even when growth factors are used. The addition of etoposide to the three-drug regimens has been evaluated only in phase I studies. Myelosuppression increases, and rates of febrile neutropenia as high as 26% have been reported. The lack of any suggestion of additional efficacy and the substantial toxicity suggest that four-drug combinations are not advisable.
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PMID:Ifosfamide and paclitaxel combinations for the treatment of advanced non-small cell lung cancer. 953 4

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

Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.
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PMID:Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. 984 84

The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.
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PMID:Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma. 1002 70

lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.
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PMID:Evaluation of ifosfamide for treatment of various canine neoplasms. 1083 May 40


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