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)

VM-26, a semisynthetic podophyllotoxin, was tested for antitumor activity and clinical toxicity in 181 children. The drug was administered iv at weekly intervals, beginning at a dose of 130 mg/2/week. The dose was increased, as tolerated, after 3 and 6 weeks to 150 and 180 mg/m2/week, respectively. The only major toxicity was hematologic, with neutropenia predominating. Anaphylaxis occurred in one patient. The drug demonstrated significant activity in acute lymphocytic leukemia (four responses among 15 patients) and neuroblastoma (ten responses among 31 patients). Objective responses were also noted in one patient each with acute myelogenous leukemia, Hodgkin's disease, histiocytic lymphoma, Wilms' tumor, Ewing's sarcoma, undifferentiated carcinoma, and sacrococcygeal sarcoma. Further trials of VM-26 in these childhood malignancies are warranted.
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PMID:Phase II study of VM-26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group. 38 Aug 3

A total of 37 adult patients with locally advanced or metastatic soft-tissue sarcoma (STS) entered a pilot study of combination chemotherapy based on the CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine) regimen, in which cyclophosphamide was replaced by ifosfamide and mesna (1 g/m2 ifosfamide given daily on days 1-5 as 2-h infusions, 1.5 mg/m2 vincristine given on day 1 as a bolus injection, 50 mg/m2 doxorubicin given on day 1 as a 5-min infusion, and 250 mg/m2 dacarbazine given daily on days 1-5 as 30-min infusions). The overall response rate in 24 patients who were evaluable for response was 46% [95% confidence interval (CI), 25%-67%] and that in subjects who had not undergone prior chemotherapy was 50% (CI, 27%-73%). In all, 4 patients achieved a complete response (17%; CI, 5%-37%) and 2 remain in remission; 3 additional subjects were surgically rendered disease-free after they had shown a partial response. Overall, 31 patients were evaluable for toxicity. Toxicity was mainly hematological; in 3 patients the nadir WBC was less than 0.5 x 10(9)/l, and in 2 cases the nadir platelet count was less than 50 x 10(9)/l. During neutropenia, infections requiring intravenous antibiotics occurred in 8 patients (26%) and in 14 of 190 cycles (7.5%); 1 of these was fatal. We conclude that this new regimen offers promise for the treatment of advanced STS, producing acceptable toxicity.
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PMID:Ifosfamide, vincristine, doxorubicin and dacarbazine in adult patients with advanced soft-tissue sarcoma. 160 May 89

Doxorubicin and ifosfamide are the two most active agents used in the treatment of advanced inoperable soft-tissue sarcoma, but their use in combination produces dose-limiting myelosuppression. To explore the feasibility of combining optimal doses of both drugs, doxorubicin (75 mg/m2) and ifosfamide (5 g/m2) were given every 3 weeks with recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF; 250 micrograms m-2 day-1) by subcutaneous injection for up to 14 days after each course. A total of 52 patients with progressive metastatic soft-tissue sarcoma were entered, none having received prior chemotherapy. One patient was ineligible and received no treatment after registration. Preliminary analysis of six cycles of chemotherapy revealed that the full protocol dose intensity had been administered to the majority of patients. Although the median leucocyte and neutrophil counts did not fall with subsequent courses of chemotherapy, the duration of neutropenia increased with each course delivered. Cumulative thrombocytopenia was a major dose-limiting toxicity and was the main reason for any dose modifications that occurred. Although 26 patients experienced infections after one or more courses of treatment, in only 7 was admission required for parenteral antibiotics. One patient died as a result of septicaemia after the first cycle of treatment. To date, there have been 22 responses (43%) with 8% complete remissions. It appears that the administration of rhGM-CSF allows this high-dose regime of chemotherapy to be given safely and the early encouraging response rate adds support to the concept that increasing the dose of doxorubicin improves the outlook for patients with advanced soft-tissue sarcomas.
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PMID:Doxorubicin plus ifosfamide with rhGM-CSF in the treatment of advanced adult soft-tissue sarcomas: preliminary results of a phase II study from the EORTC Soft-Tissue and Bone Sarcoma Group. 179 8

Trimetrexate, a lipophilic, 2,4-diaminoquinazoline derivative of methotrexate, enters cells by passive diffusion rather than via a transport system. Trimetrexate has shown promising activity in animal model systems. A total of 16 patients with metastatic soft-tissue sarcoma who had received only one prior chemotherapy regimen were treated with trimetrexate (8 mg/m2 given intravenously daily for 5 days) every 3 weeks. Treatment-related toxicity included greater than or equal to grade 2 neutropenia (8/16), thrombocytopenia (3/16), mucositis (4/16) and skin rash (3/16). No partial or complete responses were observed in 15 evaluable patients (95% confidence interval for true response rate, 0-22%) Six subjects showed stabilization of disease for periods ranging from 2 to 9 months. At this dose and on this schedule, trimetrexate appears to have little activity against refractory soft-tissue sarcomas.
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PMID:Phase II trial of trimetrexate in patients with advanced soft-tissue sarcoma. 183 Feb 49

Data from several clinical trials in patients with solid tumors clearly demonstrate that recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) is able to shorten the time period of neutropenia after chemotherapy and to reduce neutropenia-related morbidity such as infections, time in hospital, etc. A placebo-controlled, double-blind multicenter trial including 81 patients with acute lymphoblastic leukemia and non-Hodgkin's lymphoma demonstrates the efficacy of rhGM-CSF to enhance engraftment (neutrophils greater than 0.5 x 10(3)/mm3) after autologous bone marrow transplantation (p less than 0.001) and to reduce the frequency of bacterial infections (34% vs. 56%). In addition, GM-CSF is able to shift the cell cycle of myeloid leukemic cells from the G0 to S phase in vitro and in vivo, which results in an increased sensitivity to cell-cycling-dependent cytostatic agents. Dose intensification of chemotherapy in patients with soft tissue sarcoma and metastatic breast cancer is possible due to adjuvant treatment with GM-CSF and results in a higher frequency of remissions. Further controlled clinical studies are warranted to support these results.
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PMID:New therapeutic modalities for the clinical use of rhGM-CSF in patients with malignancies. 204 60

The first placebo-controlled trial of zidovudine in the management of HIV infection involved patients with the acquired immune deficiency syndrome (AIDS) following their first episode of Pneumocystis carinii pneumonia and patients with severe AIDS-related complex (ARC). Zidovudine was shown to increase survival, and the trial was terminated early at the request of an independent review board. In order to obtain more information on the long-term efficacy and tolerance of the drug the study was continued on an open-label basis where all patients were offered zidovudine. Data from this ongoing open-label study are reviewed on a regular basis. Side-effects associated with zidovudine include anaemia and neutropenia both of which are more predominant in patients with more advanced disease. Two basic strategies have been adopted with the aim of improving the therapeutic index of the drug involving (i) dose modification and (ii) combination with other antiviral or immunomodulatory compounds. Although several phase I and II studies are proceeding it is likely that research in this area will continue to expand. AIDS patients with Kaposi's sarcoma (but without a history of AIDS-defining opportunistic infection) were precluded from the original phase II trial described above. The value of zidovudine in the treatment of the sarcoma per se has yet to be established. Trials are currently in progress in this indication evaluating the potential of zidovudine administered either alone or in combination with interferon. Possibly the largest area of research is concerned with defining the role of zidovudine earlier in the course of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Current and future trials with zidovudine. 264 66

Forty-three adult patients with locally advanced or metastatic soft tissue sarcoma entered a pilot study of combination chemotherapy comprising 50 mg of doxorubicin/m2 by intravenous bolus, 850 mg of dacarbazine/m2 by 1-hour infusion, and 5 g of ifosfamide/m2 by 24-hour infusion with mesna uroprotection. The overall response rate in 40 assessable patients was 25% with two complete remissions. Twenty-four episodes of infection occurred in 148 courses (16%). These infections were usually associated with neutropenia (granulocyte count less than 0.5 X 10(9)/L), which occurred in 70% of the courses. These results do not differ from those elicited by each agent alone, and may reflect inadequacies of dose intensity or scheduling, or evaluation in a study population with adverse prognostic factors.
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PMID:Combination chemotherapy with doxorubicin, dacarbazine, and ifosfamide in advanced adult soft tissue sarcoma. Canadian Sarcoma Group--National Cancer Institute of Canada Clinical Trials Group. 277 39

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.
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PMID:Effects of Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of lymphoid neoplasms with very poor prognosis. 301 6

The regimen of doxorubicin (DOX), ifosfamide (IFF), and dacarbazine (DTIC) (AID) for previously untreated inoperable or metastatic sarcoma has acceptable toxicity with significant activity. Twenty patients received 79 courses of DOX (60-75 mg/m2) with or without DTIC (900 mg/m2) by continuous infusion over 72 hours with escalating doses of IFF and mesna uroprotection. Nineteen patients were evaluable for toxicity. Myelosuppression was dose-limiting. The maximum tolerated dose was DOX at 60 mg/m2, DTIC at 900 mg/m2, and IFF at 7500 mg/m2 per course. Of the 79 courses analyzed, 33 (42%) resulted in wbc counts less than 1000/microliter; 14 (18%) were complicated by fever and neutropenia, and three by sepsis. There were no toxic deaths. Relative platelet sparing was observed and nadirs were brief. In contrast to bolus-dose DTIC divided over 5 days, DTIC by continuous infusion did not add significantly to gastrointestinal toxicity. Nausea and vomiting was well controlled by antiemetics. Mucositis occurred sporadically. Unlike our phase II study of IFF alone, no CNS or renal toxicity was observed. No cardiac toxicity was encountered, although only four patients have received greater than 450 mg/m2 of cumulative DOX. One episode of DOX extravasation occurred despite a long iv line that extended to the axilla. No serious tissue damage was observed, perhaps due to the dilute solutions of DOX used. Partial responses were seen in eight of 18 evaluable patients (44%) and in six of 11 patients at or near the phase II level. Two additional patients with minimal response have continued tumor regression. The median number of courses before partial response was four (range, one to five). The median duration of response has not been reached (3+ to 10+ months). An inoperable primary has been rendered surgically resectable in one patient. Activity in previously untreated sarcomas should be further evaluated in a randomized phase III study against a standard DOX-containing combination.
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PMID:Doxorubicin, ifosfamide, and dacarbazine (AID) with mesna uroprotection for advanced untreated sarcoma: a phase I study. 308 17

A 57-year-old patient with chronic granulocytic leukemia in blast crisis and severe neutropenia is presented. This patient developed right sided peritonitis due to an isolated transmural granulocytic sarcoma of the terminal ileum. The affected segment was resected and the patient survived 4 more months. Thus, despite neutropenia, an aggressive surgical approach should be considered in a leukemic patient presenting with unexplained acute abdomen, since, as demonstrated here, a localized lesion which could not have otherwise been detected, was ultimately found and promptly resected.
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PMID:Acute abdomen due to granulocytic sarcoma of the terminal ileum. 318 48


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