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)

Randomized trials suggest improved disease-free survival in low-grade non-Hodgkin's lymphoma (LGNHL) when interferon is combined with multiagent chemotherapy. This phase II trial was conducted to investigate the feasibility of combining fludarabine monophosphate (fludarabine) and IFN in a regimen for treatment of LGNHL. Twenty-one patients were evaluable. Median age was 55 years, and patients had been treated with an average of 1.7 chemotherapy regimens before enrollment. Patients received 25 mg/m2 of fludarabine intravenously on days 1 through 5 followed by 2 x 10(6) U/m2 of interferon-alpha-2a subcutaneously on days 22 through 26. Cycles were repeated every 4 weeks with delays and dose modifications for significant cytopenias. Patients were restaged after cycles 4 and 8, and those with at least a partial response to therapy were given maintenance therapy consisting of 2 x 10(6) U/m2 interferon-alpha-2a subcutaneously three times per week for 6 months. The overall response rate was 76% with a 25% complete response (CR) rate. Overall response rates were 75% (3/4 with 2 CR's) for chemotherapy-naive patients and 76% (13/17 with 3 CR's) for previously treated patients. Median time to progression was 12 months, and currently two patients are without evidence of progression at a median follow-up of 55 months. Grade III or greater toxicities included neutropenia (39%), anemia (17%), thrombocytopenia (5%), fevers/chills (5%), and fatigue (5%). Fludarabine and interferon can be effectively and safely combined in a regimen with significant activity against LGNHL. A modification of this regimen may be suitable for further study.
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PMID:Phase II study of fludarabine combined with interferon-alpha-2a followed by maintenance therapy with interferon-alpha-2a in patients with low-grade non-hodgkin's lymphoma. 1215 72

We performed a phase I study combining gemcitabine and interferon (IFN)- 2b in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and recommended doses for phase II trials. Five dose levels of gemcitabine (mg/m )/IFN- (x10 IU) were planned: 500/5, 1000/5, 1000/7, 1000/10 and 1200/10. Gemcitabine was given once weekly and IFN 3 x weekly for 3 consecutive weeks followed by 1 week of rest (28-day cycles). Between February 1997 and June 1999, 21 patients with advanced pancreatic ( =3), ovarian ( =1), renal ( =10) and non-small cell lung cancer (NSCLC; =7) were enrolled. The MTD was reached at gemcitabine 1000 mg/m and IFN- 7 x 10 IU, with two of three patients having dose-limiting toxicity (thrombocytopenia). The predominant hematologic toxicities (grade 3/4) were neutropenia and thrombocytopenia (13 and five patients, respectively). Three patients had moderate neutropenic fever and one had grade 4 AST/ALT; none required hospitalization. Of the 18 evaluable patients, responses included one partial response (NSCLC) and 10 stable diseases (eight renal cancer). We conclude that the recommended phase II study regimen is gemcitabine 1000 mg/m and IFN- 5 x 10 IU, every 28 days. The results, particularly those in metastatic renal carcinoma, are encouraging and worthy of further evaluation in phase II trials.
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PMID:Gemcitabine and interferon-alpha 2b in solid tumors: a phase I study in patients with advanced or metastatic non-small cell lung, ovarian, pancreatic or renal cancer. 1239 52

Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/microL and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection. Constitutional neutropenia, which is common among blacks, should not exclude patients from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections.
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PMID:Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. 1283 10

Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
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PMID:Side effects of therapy of hepatitis C and their management. 1240 99

Imatinib mesylate (STI571) is a highly effective and well-tolerated treatment for patients with chronic-phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty-three chronic-phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6-19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1-4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3-4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non-haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic-phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic-phase CML patients with a previous history of intensive treatment.
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PMID:Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation. 1258 Sep 69

More than 4 million people in the United States are infected with hepatitis C virus (HCV). During the next 20-30 years, the burden of HCV-related mortality and morbidity will likely double. To date, the most effective treatment for chronic HCV infection is the combination of either interferon (IFN)-alpha or pegylated IFN-alpha and ribavirin. For a sustained virologic response, treatment adherence and dose maintenance are essential. However, both IFN-alpha and ribavirin induce hematologic toxicity, such as anemia, neutropenia, and thrombocytopenia, which can compromise treatment adherence and dose maintenance and could, therefore, potentially influence outcomes. Although there are currently no approved treatments for hematologic complications of HCV therapy, studies have shown that hematopoietic growth factors can provide significant benefits. This review highlights the pharmacology, risks, and benefits of recombinant hematopoietic growth factor therapy in HCV-infected patients.
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PMID:Hematologic disorders associated with hepatitis C virus infection and their management. 1503 43

The efficacy and secondary effects of an induction dose of interferon-alpha2b (IFN-alpha2b) with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C infection were compared. A prospective study was undertaken between March 1998 and November 2001 in which 84 Spanish hospitals took part. Six hundred and fourteen naive patients (age range 18-65 years) diagnosed with chronic hepatitis C virus (HCV) infection and without cirrhosis or co-infection by other viruses, were included. Patients were divided into two groups. Group A (n = 304) received induction treatment with a daily dose of 5 MU of IFN-alpha2b for 4 weeks, followed by 5 MU three times a week with ribavirin (1000-1200 mg/day, according to weight) until completing 1 year of treatment. Group B (n = 310) received the standard dose of IFN-alpha2b of 3 MU three times per week for 48 weeks together with ribavirin (1000-1200 mg/day, according to weight). Both groups were completely comparable according to age, gender, body weight, transaminase levels, genotype, viral load and hepatic inflammatory activity (Knodell Index). No control group was included for ethical reasons. Pegylated interferon was not available at the time of the study. Serum baseline samples were collected for the determination of genotype. Samples were also collected at baseline, weeks 4, 12, 24, 48 and 72, in order to detect and quantify HCV-RNA. The efficacy of treatment was evaluated by means of sustained viral response (SVR) characterized by persistent negativity of HCV-RNA at the end of the follow-up period. At week 4, the response to treatment was greater in group A (49.6%) compared with group B (34.5%) (P = 0.0002), and was maintained until week 12 (64.1% compared with 55.8% respectively) (P = 0.03). These differences disappeared at week 24, when group A (69%) was compared with group B (65%) (NS). At week 48, the response rate for group A was 50.6% compared with group B 47.4% (NS), and at week 72, the SVR in group A was 46% compared with 40.3% for group B (NS). The global SVR was 43.1%. On analysing the response to treatment according to genotype and viral load, we found that the induction treatment was slightly superior in patients with genotype 1 and an elevated viral load (>2 x 10(6) copies/ml). They achieved a SVR in group A of 39.1% compared with 25.5% in group B (P < 0.05). However, this slight improvement obtained in group A, was achieved at the expense of a greater percentage of dropouts compared with group B (6.4% vs 2.2%, P < 0.01); a greater rate of side effects (58.5 vs 36.7%, P < 0.05) and also a greater percentage of neutropenia (3.1% vs 0.9%, P < 0.05). The induction treatment presented a better initial response, but this was not maintained at the end of treatment, and did not improve the results obtained with the standard treatment. Although the patients with genotype 1 and elevated viral load had a better response with the induction treatment, this was accompanied by a greater percentage of dropouts and secondary effects. It would be interesting to repeat this type of study in the future, using pegylated interferon.
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PMID:Comparative study of the efficacy of an induction dose of interferon-alpha2b with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C. 1463 77

Management of HCV infection and related liver disease with treatment currently available lead to a sustained virological response in 20% of patients using interferon (IFN)-alpha mono-therapy and approximately 40-45% in those on combination therapy with ribavirin.The aim of the present investigation was to compare the effect of consensus interferon alphacon-1 (C-IFN), and IFN-alpha 2b plus ribavirin, in patients relapsing after treatment with interferon alone. A total of 112 randomised patients with relapsing HCV infection (M/F=53/59), were treated for 24 weeks with: (A) IFN-alpha 2b starting with 5/6MU/day till negativity of HCV-RNA followed by 3MU every other day, plus ribavirin 15mg/kg/day (n=34); (B) C-IFN 9microg/day (n=40); (C) ursodeoxycholic acid (UDCA; sodium salt) 450mg/day (n=37). At the end of treatment, patients were observed at follow-up for 24 weeks.Clearance of HCV-RNA was achieved by the end of treatment in 23 patients (68%) in Group A and 21 also showed a biochemical response with normal ALT; in Group B, 33 patients (82%) had both a virological and a biochemical response; in Group C, one patient cleared HCV-RNA. At the end of follow-up (sustained-response), 29% of patients in Group A (n=10/34) had negative PCR (seven patients relapsed at the 4th week, six at the 12th); in Group B, a sustained response was achieved in 58% (p<0.03; two patients relapsed at the 4th week, three at the 12th and five at the 24th).MAJOR SIDE EFFECTS COMPRISED: neutropenia (n=17) and decrease in Hb>1.5g/dl (n=33) in Group A, recurrence of psoriasis in two patients in Group B and abdominal discomfort and diarrhoea in 11 patients in Group C.Rapid clearance of circulating HCV-RNA was induced by C-IFN (66% at three weeks, 71% at six weeks): this was a good prognostic index both for end of treatment and sustained response. Treatment with C-IFN lead to a higher response rate compared to that of recombinant IFN-alpha 2b in association with ribavirin. The action of C-IFN is superior in the time taken to reach the maximal response rate during treatment and in the lower prevalence of relapse of the infection.
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PMID:Consensus interferon versus interferon-alpha 2b plus ribavirin in patients with relapsing HCV infection. 1466 12

We assessed the activity and safety of a biochemotherapy regimen in which courses of paclitaxel, methotrexate, and cisplatin were alternated with courses of 5-fluorouracil, alpha-interferon, and cisplatin in the treatment of refractory urothelial carcinoma. Forty patients were enrolled in the study. In the phase I portion, 15 patients were treated according to an escalating dosage regimen designed to determine the maximum tolerated dose. A total of 30 patients received treatment according to the maximum tolerated dose regimen: methotrexate (30 mg/m(2)) given iv on days 1 and 22; paclitaxel (175 mg/m(2)) given iv over 3 h on day 1; cisplatin (70 and 25 mg/m(2)) administered iv on days 1 and 22, respectively; 5-fluorouracil (400 mg/m(2)) given iv by continuous infusion daily for 5 days beginning on day 22; and alpha-interferon (4 mIU/m(2)) given SC daily for 5 days simultaneously with the 5-fluorouracil infusions. The regimen was repeated at 42-day intervals. The 40 treated patients had an overall response rate of 43%, a complete response rate of 18%, and a median survival time of 44 weeks. Most of the toxic effects were hematologic: Grade 4 neutropenia occurred in 30% of patients (12 patients) and Grade 3 thrombocytopenia in 20% (8 patients). Even though this alternating biochemotherapy regimen was active for patients with refractory urothelial carcinoma, its activity was not better than that of certain single cytotoxic agents. Furthermore, the complicated dosing schedule and toxic effects of the regimen precluded its routine use in the treatment of urothelial carcinoma.
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PMID:Treatment of refractory urothelial carcinoma with alternating paclitaxel, methotrexate, cisplatin (TMP) and 5-fluorouracil, alpha-interferon, cisplatin (FAP). 1467 May 40

(1) Three versions of interferon alfa are marketed in France for the treatment of chronic hepatitis C, namely alfa-2a, alfa-2b, and alfacon-1. When used in combination with ribavirin, the three drugs have similar risk-benefit ratios. (2) Two pegylated forms are now also available, namely peginterferon alfa-2a and peginterferon alfa-2b. (3) The clinical evaluation dossier contains data from four trials comparing peginterferon alfa alone with standard interferon alfa alone, and two trials comparing peginterferon alfa + ribavirin combinations with standard interferon alfa + ribavirin. (4) In terms of virological and biochemical outcomes, the peginterferon was more effective than the corresponding standard interferon when either drug was used alone. (5) In patients infected with genotype 1 hepatitis C virus, and a low viral load, the peginterferon + ribavirin combination was more effective than the standard interferon + ribavirin combination at reducing viral load below the limits of detection. (6) Pending comparative trials, there is no evidence of any difference in efficacy between peginterferon alfa-2a and peginterferon alfa-2b. (7) It is not yet clear whether peginterferon has any favourable impact on hepatic histological outcomes compared with standard interferon. (8) Except for a dose-dependent increase in the risk of neutropenia, the safety profile of peginterferon does not seem markedly different from the safety profile of standard interferon. (9) Like standard interferon alfa, peginterferon alfa is injected subcutaneously, but only once a week (instead of three times a week). (10) The use of peginterferon alfa-2 in France multiplies drug costs by a factor of three compared with standard interferon alfa-2. (11) In practice, the use of peginterferon alfa instead of standard interferon alfa is justified mainly for patients infected with genotype 1 who have a low viral load. Other patients may appreciate the smaller number of injections.
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PMID:Pegylated interferon: new preparation. Chronic hepatitis C: advantageous for some patients, but more data needed. 1498 84


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