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)

Pegylated liposomal doxorubicin is associated with a lower risk of cardiotoxocity than conventional formulations of doxorubicin, allowing the use of higher cumulative doses. In this Phase II study, 25 patients aged over 70 years (median 79, range 75-82 years) with aggressive non-Hodgkin's lymphoma (NHL) (International Prognostic Index (IPI) -2, 12 (48%); IPI-3, 10 (40%); IPI-4, 3 (12%)) received CHOP with pegylated liposomal doxorubicin. All completed 6 treatment cycles and were evaluable for efficacy and safety. A complete response was achieved in 13 (52%) patients and a partial response in 12 (48%) patients, which was maintained for at least 12 months. The median time to progression was 26 months (range 14->42) and median overall survival was 32 months (range 26-48). No Grades III/IV toxicity occurred; adverse events included neutropenia, anaemia, nausea and vomiting, diarrhoea and constipation in 16-29% of the cycles. Pegylated liposomal doxorubicin is an effective and well-tolerated component that may be substituted for doxorubicin in the CHOPC (cyclophosphanide, doxorubicin, vincristine, prednizolone) regimen for the treatment of aggressive NHL in elderly people.
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PMID:Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stages III/IV) non-Hodgkin's lymphoma. 1216 80

The purpose of this study was to determine the efficacy of salvage chemotherapy with, P-IMVP-16/CBDCA, consisting of carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX), for patients with aggressive non-Hodgkin's lymphoma (NHL) who had previously received CHOP [a regimen of cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisolone], as first-line chemotherapy. The 45 consecutively enrolled patients received methylprednisolone (mPSL) 1000 mg per body for 3 d (from day 1 to day 3), IFM 1000 mg/m(2) for 5 d (from day 1 to day 5), MTX 30 mg/m(2) on day 3 and day 10, VP-16 80 mg/m(2) for 3 d (from day 1 to day 3), and CBDCA 300 mg/m(2) on day 1, with granulocyte colony-stimulating factor every 21 d. Patients 70 yr of age or older were given 75% of the standard dose. The response rate [complete response (CR) plus partial response (PR)] was 55.6% (25/45), including 12 (26.7%) CR and 13 (28.9%) PR. The overall survival rate for the 45 patients was 31.1% at 1 yr and 17.3% at 2 yr. The failure-free survival rate for the 45 patients was 6.7% at 1 yr and 4.4% at 2 yr. The survival rate for the 25 responders was 48.0% at 1 yr and 24.0% at 2 yr, and the survival rate for the 20 non-responders was 10.0% at 1 yr (P<0.001). Multivariate analysis demonstrated that prior chemotherapy (reduced-dose CHOP for age 70 yr or older) and the number of cases of extranodal involvement (>1) were significant unfavorable factors for overall survival. Although the major toxicity was neutropenia, no patient died of infection related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable. Unfortunately, the clinical outcome with P-IMVP-16/CBDCA was unfavorable, possibly because the study comprised consecutive patients who had received identified intensive chemotherapy, such as biweekly CHOP. Salvage chemotherapy with P-IMVP-16/CBDCA is not sufficient to cure relapsed or refractory aggressive NHL. Aggressive NHL should be cured by first-line chemotherapy with or without hematopoietic stem cell transplantation.
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PMID:A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin's lymphoma who had previously received CHOP therapy as first-line chemotherapy. 1222 93

Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled, 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study ofsequential administration of topotecan 1.25 mg/m2 days 1-5 and etoposide 50 mg po b.i.d. days 6-12, every 28 days without G-CSF. Most patients had diffuse large B-cell lymphoma and all had received only one prior regimen (CHOP, 20 patients, or equivalent, 2 patients). Patients with stable or responding disease were allowed to proceed to high-dose therapy and autologous stem-cell transplant after 2 cycles of therapy. The 22 patients received a total of 62 cycles of topotecan + etoposide (median 2, range 1-6), and 4/22 completed all six planned cycles. Hematologic toxicity was significant and resulted in incomplete etoposide dosing in half of all cycles in 16/22 patients. Nineteen of twenty-two patients had grade 3/4 neutropenia, 12 had grade 3/4 thrombocytopenia, and 6 grade 3/4 anemia. Eleven patients had at least one episode of febrile neutropenia or had documented infection. Non-hematologic toxicity was mild. Four patients had a partial response (PR) (18.2%), nine had stable disease and seven progressed; three patients with stable disease went on to ABMT. The combination of topotecan and etoposide as given in this study has modest activity in relapsed/refractory aggressive histology NHL, and produces marked myelosuppression. Other doses and schedules combining topo I and II inhibitors, or topo I inhibitors with alkylating agents, should be explored with the addition of hematopoietic growth factors in this patient population.
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PMID:Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin's lymphoma: a National Cancer Institute of Canada Clinical Trials Group study. 1240 Jun

Elimination of tumor cells from hematopoietic stem cell products is a major goal of bone marow-suported high-dose cancer chemotherapy. In patients (pts) with low-grade lymphoma Gianni et al (2000) assessed the ability of Rituximab, given in combination with high-dose chemotherapy, to eradicate PCR-detectable disease and enable the harvesting of large amounts of uncontaminated circulating progenitor cells. Our study was conducted in 27 consecutive pts with untreated bcl2 positive NHL (follicular lymphoma--7, chronic lymphocytic leukemia--13 and NHL in leukemic phase--7), 14 pts received Rituximab. Patients received 4 courses of standard-dose chemotherapy (CHOP or FLU-CY), followed by one course of high-dose cyclophosphamid plus G-CSF. Patients allocated to Rituximab received i.v. infusions of 375 mg/m2 48 hours before stem cell collection and in 3 weekly doses after transplantation (R-CHT). Clinical response after transplantation was evaluated in 26 pts who completed the treatment. The complete response rate was in 100% in the Rituximab group (PCR negative in 79%) versus 50% of controls (p<0.01). Yield of purged CD34+ cells was with median 5.23x10(6)/kg in CHT and 8.76x10(6)/kg in R-CHT pts. Toxicity in the both arms was acceptated (no difference). No significant difference was observed between CHT and R-CHT group in the mean number of days spent with neutropenia and trombocytopenia. After a follow-up of 31 months, no patient relapsed. Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical (100%) and molecular remission in 79% of evaluable pts. We showed that Rituximab in combination with effective high-dose anti- lymphoma chemotherapy, allowed the harvesting of large amounts of tumor free progenitor cells in evaluable pts.
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PMID:Efficiency of in vivo purging with autologous stem cell transplantation and monoclonal antibody in B-cell lymphomas. 1268 74

The aim of this study is to verify the feasibility and the clinical activity of a new CHOP-like schedule (ACOD) with a fractionated days 1 and 8 administration in elderly patients. This regimen was chosen in the attempt to allow a sufficient dose intensity (DI) of each drug with better compliance. Fifty-two patients, (74 years, median age), with diffuse large B cell non-Hodgkin's lymphoma were retrospectively evaluated. Patients received ADM 25 mg/sqm, CTX 500 mg/sqm, VCR 1.2 mg/sqm (max 2 mg intravenously) days 1 and 8 and PDN 50 mg orally, days 1-8. Results showed that 54% of patients reached a complete remission, 21% a partial remission with an overall response rate of 75%. Two-thirds of the patients received at least 70% of the planned dose of cyclophosphamide and doxorubicin and 50% of vincristine and prednisone. The median duration of follow up was 12.6 months (range 0.7-61.4). The estimated median OS was 15.2 months (95%CI = [11.6, not estimable]); the estimated median PFS was 5.7 months (95%CI = [5.12, not estimable]). After 2 years, the proportion of patients alive was 47% (95%CI = 34-64%) and the proportion of patients free from progression was 39% (95%CI = 27-57%). Grade 3-4 leukopenia was observed in 61% of patients with 11% of febrile neutropenia. In conclusion, the ACOD chemotherapy regimen seems safe and feasible in elderly patients. This schedule allowed a sufficient DI of chemotherapic agents with clinical results very similar to those recorded with the standard CHOP regimen in young adults.
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PMID:ACOD, a modified CHOP regimen for elderly patients with aggressive non-Hodgkin's lymphoma. 1280 17

This study was designed to evaluate the feasibility, toxicity, and efficacy of rituximab added to the VNCOP-B (etoposide/mitoxantrone/cyclophosphamide/vincristine/prednisone/bleomycin) combination regimen for the treatment of elderly patients with large B-cell lymphoma. Previously untreated patients > or = 65 years of age with stage II, III, or IV large B-cell non-Hodgkin's lymphoma were treated with a modified VNCOP-B regimen with weekly chemotherapy for 8 weeks. In addition, patients received rituximab 375 mg/m2 intravenously on weeks 1, 2, 3, 4, 6, and 8. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) during the 8 weeks of treatment. Between August 1999 and February 2002, 41 patients entered this multicenter phase II trial. The median age was 74 years, and 54% of patients had high-risk tumors (age-adjusted International Prognostic Index scores of 2 or 3). Sixty-eight percent of patients completed the 8 weeks of therapy. Overall response rate was 66%; actuarial progression-free survival rate at 2 years was 59%, with a 57% actuarial overall 2-year survival rate. Patients > or = 75 years of age had similar treatment outcomes compared with younger patients. Toxicity with this regimen was predominantly related to chemotherapy; rituximab was well tolerated. Grade 3/4 neutropenia occurred in 83% of patients even with routine use of prophylactic G-CSF or GM-CSF. Treatment-related death occurred in 4 patients (10%). VNCOP-B plus rituximab is efficacious, producing 2-year progression-free survival rates that compare favorably with those of other active regimens in this patient group. Hematologic toxicity was increased compared with previous reports with VNCOP-B alone, as evidenced by the treatment-related mortality rate of 10% in the present study. Differences in toxicity may have been caused by the addition of rituximab, the modified etoposide schedule, or the differences in patient characteristics. This regimen provides a treatment option for elderly patients who are not considered candidates for standard CHOP/rituximab chemotherapy.
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PMID:First-line treatment with brief-duration chemotherapy plus rituximab in elderly patients with intermediate-grade non-Hodgkin's lymphoma: phase II trial. 1283 53

Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by injection to maintain its effects on the bone marrow. Pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) is a longer-acting, self-regulating form of filgrastim created by the covalent linkage of a 20-kd polyethylene glycol molecule to the N-terminal of the filgrastim molecule. The molecular characteristics of pegfilgrastim result in a longer terminal half-life, making once-per-chemotherapy-cycle administration possible. The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. Pegfilgrastim has also been shown to be comparable to filgrastim in reducing neutropenic complications in patients treated with chemotherapy for lymphoma. Data from three clinical trials have been presented: a randomized controlled trial in elderly patients treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) for relapsed or refractory non-Hodgkin's lymphoma; a randomized controlled trial in patients treated with ESHAP (etoposide/methylprednisolone/cisplatin/cytarabine) for relapsed or refractory lymphoma; and a study in patients with newly diagnosed non-Hodgkin's lymphoma. The safety profile of pegfilgrastim is comparable to that of filgrastim in the clinical settings studied to date. The once-per-cycle administration of pegfilgrastim may improve patient quality of life because it is less disruptive to patients and caregivers, and increase adherence because no doses are missed, thus further advancing the management of chemotherapy-induced neutropenia and its consequences.
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PMID:Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia. 1450 17

Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol (PEG) is covalently bound at the N-terminal residue resulting in decreased renal clearance and increased plasma half-life compared with filgrastim. This open-label, randomized, phase 2 study compared two doses of single administration pegfilgrastim (60 and 100 microg/kg) with daily doses of filgrastim (5 microg/kg/day) or no cytokine treatment after standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for non-Hodgkin's lymphoma in 50 elderly patients. The primary endpoint was the duration of grade 4 (severe) neutropenia (absolute neutrophil count < 0.5 x 10(9)/l) in cycle 1. Duration of grade 4 neutropenia in cycle 1 was 2.2 (SD 1.2), 1.5 (SD 1.1), 0.8 (1.2) and 5.0 (2.0) days for patients who received pegfilgrastim 60 microg/kg, pegfilgrastim 100 microg/kg, filgrastim 5 microg/kg and no cytokine, respectively. The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former. When the treatment groups were balanced for these risk factors, duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 microg/kg and filgrastim patients with and without these risk factors, respectively. The incidence of febrile neutropenia (defined as ANC < 0.5 x 10(9)/l and temperature > 38.2degrees C) was low (10% of patients). Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim. Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting.
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PMID:Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma. 1456 51

Twenty-nine patients with non-Hodgkin's lymphoma received a single subcutaneous injection of 6 mg pegfilgrastim approximately 24 h after the start of CHOP chemotherapy. The safety of pegfilgrastim in this patient population was determined by reports of adverse events. The pharmacokinetics of pegfilgrastim were characterized and the duration of grade 4 neutropenia, time to absolute neutrophil count (ANC) recovery to > or = 2.0 x 10(9)/l, neutrophil nadir, and incidence of febrile neutropenia were determined in the first 21-day chemotherapy cycle. The incidence of grade 4 neutropenia in cycle 1 was 43% with a mean (SD) duration of grade 4 neutropenia value of 1.0 (1.4) day. No apparent relationship between the duration of grade 4 neutropenia and body weight was observed. The median [quartiles] time to ANC recovery was 10 [9, 11] days. The incidence of febrile neutropenia was 11%. No unexpected adverse events were reported and no patient developed antibodies to pegfilgrastim. Serum concentration of pegfilgrastim reached a maximum (median [quartiles]) of 128 [58, 159] ng/ml at approximately 24 h after administration, and was followed by a second smaller peak (median [quartiles]) of 10.6 [3.0, 20.5] ng/ml at the time of the neutrophil nadir. After the second peak, concentration of pegfilgrastim declined linearly with a median terminal half-life of approximately 42 h.
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PMID:Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin's lymphoma. 1469 20

We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.
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PMID:Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy. 1495 49


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