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)

In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH levels and lymphoma size and randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen. RhGM-CSF significantly reduced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements. Complete response rates were 63% for all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group. Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-CSF arm. However, there were no significant differences in overall survival between the GM-CSF treatment and control groups (21 vs. 23 months). Early relapse rates were markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen. Thus, GM-CSF abates toxic side effects of chemotherapy and may help to maintain dose intensity in high-risk hNHL.
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PMID:Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF. 751 44

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

A 52-year-old man, who complained of tarry stool and systemic lymphadenopathy, was admitted to our hospital on July 2, 1992. Biopsy showed diffuse large cell lymphoma. Leukocytosis with atypical lymphocytes was not shown in the peripheral blood, but there was an elevated serum LDH level. The man was found to have both HTLV-I antibody and the monoclonal integration of proviral DNA in malignant lymph node cells obtained at biopsy. The diagnosis was lymphoma-type adult T-cell leukemia (ATLL). The chemotherapy regimens of MI-FP, CHOP and modified DHAP were used for the treatment, but were not effective. So, he was treated with etoposide 75 mg orally for 25 days (chronic oral etoposide therapy) and achieved partial remission. This chemotherapy induced myelosuppression with neutropenia, but there was no documented infection. Chronic oral etoposide therapy is an effective regimen for patients with relapse or refractory lymphoma.
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PMID:[Adult T cell leukemia/lymphoma effectively treated with chronic oral etoposide]. 837 79

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.
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PMID:[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)]. 902 Sep 48

The results of chemotherapy remain unsatisfactory for many patients with advanced lymphomas. Both standard and more aggressive chemotherapy regimens might have their respective role in the management of theses diseases. We have tested the feasibility and assessed the toxicity and activity of a LNH84-derived chemotherapy for aggressive non-Hodgkin's lymphoma in two general hospitals. Thirty-three untreated patients were included over a period of 4 years. Median age was 39 years, 21 were male. International Working Formulation was F for 2 patients, G for 17, H for 8, I for 1, J for 4, one unclassified. Seventeen patients had B symptoms, 15 stage IV, 8 bulky disease, 21 abnormal LDH, 5 performance status > or =2. The overall response rate was 93%. The single treatment related death resulted from bleomycin acute pneumonitis. Neutropenia WHO grade 4 occurred in all patients, resulting in infections grade 3 in 12 and thrombocytopenia grade 4 in 3. In the induction phase, courses could never be repeated day 14. The dose intensity of the four drugs contained in this phase is thus calculated between 64.5 and 81.5%. At 3 years, overall survival is 80% and event-free survival is 62%. This LNH84-derived regimen is effective. However, the induction phase is toxic and a 3-weekly interval appears more appropriate. Such intensive treatment might benefit patients with very aggressive lymphomas and this should be studied in randomized comparison against standard CHOP.
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PMID:Feasibility, toxicity, and activity of LNH84-derived chemotherapy in the management of aggressive lymphomas. 925 80

In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.
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PMID:Combination salvage chemotherapy with MIZE (ifosfamide-mesna, idarubicin and etoposide) for relapsing or refractory lymphoma. 938 66

Following its introduction into the market, PAPM/BP (panipenem/betamipron) was clinically studied in 188 evaluable cases out of 207 cases primarily of respiratory infectious diseases treated at the pediatric departments of 15 hospitals. In the clinical evaluation, the drug proved effective in three of three cases of sepsis; three of three cases of suppurative meningitis; nine of ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63 cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of phyothorax, all of which are respiratory infectious diseases; one of one case of secondary infection of a chronic respiratory disease; and two of two cases of lymphadenitis, which is a disease of the soft dermal structure. The overall efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram-positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31 strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes. Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae (88.2%), three of four strains of M. catarrhalis, and two of two strains of K. pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23 strains of S. pneumoniae that were examined, penicillin-resistant strains accounted for 56.5%, showing an elimination rate of 100%. No serious adverse effects were observed, and the incidence of adverse effects was 1.45%. As for abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case (0.51%). These results suggest that PAMP/BP could be considered the first choice in the treatment of infectious diseases in pediatrics, due to its effectiveness and high level of safety.
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PMID:[Clinical and bacteriological studies on panipenem/betamipron in pediatrics. Kanagawa Research Group for Infectious Diseases of Children]. 964 2

Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors.
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PMID:Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. 1057 56

The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC < or = 0.5 x 10(9)/l) and febrile neutropenia (FN, an ANC < 0.5x10(9)/l in association with a body temperature of > or = 38.3 degrees C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged > or = 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibility included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of > or = 38.3 degrees C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had > or = 2 extranodal diseases, 59% had serum LDH > 1 x normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of < or = 3.5 g/dl, serum LDH > 1 x normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5-90.7) (high risk), 23.9% (95% CI, 12.6-38.8) (intermediate risk) and 4.4% (95% CI, 0.5-15.1) (low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4-83.5), 17.4% (95% CI, 7.8-31.4) and 2.2% (95% CI, 0.05-11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (> or = 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated.
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PMID:A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma. 1075 86

Vinorelbine (Navelbine is a semisynthetic vinca alkaloid devoid of serious neurotoxicity. When given weekly vinorelbine has documented activity against many tumors, including lymphomas. Since weekly schedules cannot be easily incorporated in combination regimens, we tested an infusional schedule of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve, HIV or other serious infection, central nervous system disease, or prior stem cell or bone marrow transplantation were ineligible. In the phase I part, patients received a constant intravenous bolus of 8 mg/m(2), followed by intravenous continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m(2) /d in successive three-patient cohorts. Cycles were repeated every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the continuous dose of 14 mg/m(2) /d. Consequently, for the Phase II trial the starting continuous infusion dose was 12 mg/m(2) /d. After the first 19 patients were entered in the phase II study, the starting infusion dose was reduced to 10 mg/m(2) /d because of frequent grade (3/4) myelosuppression and mucositis. Forty-four patients were entered in the phase II study, of whom 41 are evaluable. Median age was 61 years, 23 were males, with clinically aggressive non-Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Disease in one patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and to the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 2(1/4)1, and serum beta(2) -microglobulin > 3.0 mg / L in 16/31 patients. Responses were observed in four of 22 patients with aggressive NHL (18%, 95% confidence interval 5%-40%), and in six of 18 with indolent NHL (33%, 95% confidence interval 13%-59%). Median progression-free survival was 6 months for responders. During the Phase II trial 114 vinorelbine courses were administered. Neutrophil nadir was < 1000/microl in 65% and < 100/microl in 35% of courses, respectively. Platelet nadir was < 100,000/microl in 30% and < 20,000/microl in 8% of courses, respectively. Grade (3/4) mucositis was seen in 18% of courses, and neutropenic fever in 13%, and was complicated by death in one patient. We conclude that this dosage and schedule of vinorelbine has modest activity in patients with relapsed or refractory NHL. Myelosuppression is frequent but reversible, but there is no significant neurotoxicity. The role of vinorelbine in combination regimens for patients with relapsed lymphomas, particularly those of indolent histology, should be further investigated.
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PMID:Infusional vinorelbine in relapsed or refractory lymphomas. 1134 9


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