Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ara-CMP-Stearate (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, YNK 01, Fosteabine) is the orally applicable prodrug of cytosine-arabinoside (Ara-C). During a phase I study in patients with advanced low-grade non-Hodgkin lymphomas or acute myeloid leukemia, the pharmacokinetic parameters of Ara-CMP-Stearate (kindly provided by ASTA Medica, Frankfurt, Germany) were determined by HPLC analysis. Seventy-two hours after a first starting dose which served for the determination of baseline pharmacokinetic parameters, Ara-CMP-Stearate was administered over 14 days by daily oral application. Ara-CMP-Stearate was started at a dose of 100 mg/day and was escalated in subsequent patients to 200 mg/day and 300 mg/day. Plasma and urine concentrations of Ara-CMP-Stearate, Ara-C and Ara-U were measured during the initial treatment phase and within 72 h after the end of the 14-day treatment cycle. So far six patients have been treated with 100 mg/day, three with 200 mg/day and another six with 300 mg/day. One patient was treated consecutively with 100 mg, 300 mg and 600 mg. Fitting the results of the plasma concentration measurements of Ara-CMP-Stearate to a one-compartment model, the following pharmacokinetic parameters were obtained (average and variation coefficient VC). Ara-CMP-Stearate dose-independent parameters: lag time = 1.04 h (0.57); tmax = 5.72 h (0.30); t1/2 = 9.4 h (0.36). Dose-dependent parameters: at 100 mg: AUC = 1099 ng/h/ml (0.31); concentration(max) = 53.8 ng/ml (0.28); at 200 mg: AUC = 2753 ng/h/ml (0.32); concentration(max) = 154.8 ng/ml (0.46); at 300 mg: AUC = 2940 ng/h/ml (0.66); concentration(max) = 160.0 ng/ml (0.59). The long lag time and late tmax can be explained by resorption in the distal part of the small intestine. No Ara-CMP-Stearate was detected in urine samples (limit of detection = 500 pg/ml). Pharmacokinetic parameters of Ara-C following Ara-CMP-Stearate application showed the following characteristics: t1/2 = 24.3 h (0.39); AUC (100 mg) = 262 ng/h/ml (0.93); AUC (200 mg) = 502 ng/h/ml (0.87); AUC (300 mg) = 898 ng/h/ml (1.07). Since Ara-CMP-Stearate causes intravascular hemolysis after intravenous administration, it was not possible to determine its bioavailability by comparing the AUC after oral and i.v. application. Instead, the renal elimination of Ara-U, as the main metabolite of Ara-C was measured during the first 72-h period and after the last application.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetics of Ara-CMP-Stearate (YNK01): phase I study of the oral Ara-C derivative. 759 74

Twenty five children with newly diagnosed Hodgkin's disease were clinically staged and treated with a chemotherapy protocol designed to reduce delayed toxicity. Four patients without macroscopic residual disease after biopsy received three cycles of hybrid EVAP/ABV. All remain in CR 31-46 months from diagnosis. One other developed fever and rash considered to be due to Ara-C and was treated with MOPP. Twenty patients had macroscopic residual disease after biopsy and were treated with two cycles of EVAP alone and reassessed with imaging and gallium scans. Twelve achieved CR, seven PR and one was not evaluable. Patients in CR were subsequently treated with 2-4 cycles of hybrid EVAP/ABV, while those in PR received 3-4 cycles. At a median follow up of 37 months the overall survival was 100%, relapse free 79% and treatment failure free 60%. Eight patients had mediastinal widening > 1/3 thoracic width. At the completion of the protocol five achieved CR, two PR and one was withdrawn from study at investigator preference. One patient has subsequently relapsed. Of the evaluable ten patients without a mediastinal presentation all achieved CR but three relapsed at 10, 13 and 18 months from diagnosis. Patients who achieved a PR only, relapsed or were withdrawn from study have been salvaged with MOPP or Ch1VPP chemotherapy.
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PMID:A pilot study of EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease. 767 78

Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13 patients with Hodgkin's disease, were treated with a combination of high dose Ara-C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2 continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to 750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky performance status was 80 (range 60-100). Patients treated included: primary refractory six, first relapse 14, > first relapse seven, and resistant relapse six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23 patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in patients who were refractory to previous chemotherapy and occurred in all sites. Toxicity was tolerable with most patients not requiring hospitalization following chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the other of a sudden death. Severe mucositis was not observed. High dose etoposide based salvage chemotherapy offers a greater probability of response than lower dose etoposide. This regimen is well tolerated and can be administered with relatively brief hospitalization.
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PMID:Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in patients with refractory or relapsed lymphomas. 815 47

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.
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PMID:BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma. 937 59

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.
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PMID:Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells. 981 88

Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as well as two patients with NHL underwent allogeneic marrow transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or unrelated donors. Patients received preparative regimens according to the baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients conditioned traditionally with Bu/Cy. For GVHD prevention, patients received cyclosporin-A (CsA) with short course methotheraxe according to the Seattle protocol. Significantly better overall survival rates were associated with the Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole. Autologous stem cell transplantation (bone marrow and/or peripheral blood) were performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with AML and two patients with NHL were conditioned with TBI/Cy and the others with BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma-free survivors. One patient relapsed having conventional chemotherapy and interferon maintenance therapy. One patient died in a rapid relapse five months post-BMT.
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PMID:Haemopoietic cell transplantation activity and results: a single institution experience. 991 38

Methotrexate (MTX) is the chemotherapeutic for which the serum levels can be detected. If the MTX level is detected in time, high toxicity risk can be decreased. In this study, intermediate doses of MTX (1 g/m2) infusions are administered to B-cell non-Hodgkin lymphoma patients between 3 and 13 years old. The toxicity of MTX in accordance with serum levels and the toxicity of other combined drugs are investigated. Blood samples were collected consecutively, and MTX levels were detected by high-performance liquid chromatography. When hematological, gastrointestinal, and renal toxicity scores were compared with the 24-h serum levels of MTX, they showed a significant positive correlation. Hematological toxicity scores increased by Ifosfamide, Etoposide, and Cytarabine combined with MTX without altering the serum levels. Antibiotic combination with MTX has no effect on the toxicity scores. In conclusion, if MTX is combined with other myelosuppressive, hepatotoxic, and nephrotoxic drugs, the measurement of MTX serum levels alone is not a sufficient parameter to show the toxicity.
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PMID:Intermediate dose of methotrexate toxicity in non-Hodgkin lymphoma. 1018 22

Patients with Hodgkin's disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin's disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin's disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of </=6 months, predicted a poor response to ASHAP. A short program of treatment with ASHAP is an effective tumor debulking approach in patients previously treated with both or either ABVD and MOPP, before ABMT.
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PMID:ASHAP: a regimen for cytoreduction of refractory or recurrent Hodgkin's disease. 1033 68

Preliminary clinical trials suggest that iodine-131 ((131)I)-labeled anti-CD20 monoclonal antibodies (MAbs) are effective single agents for the treatment of relapsed non-Hodgkin's B-cell lymphomas. However, despite high initial response rates, most patients treated in this manner will eventually relapse. We hypothesized that regimens combining (131)I-anti-CD20 antibodies with standard chemotherapeutic agents may provide synergistic anti-tumor effects, and may improve the durability of responses in patients with lymphoma. To identify promising agents for clinical testing, we assessed the in vitro cytotoxicity of combinations of (131)I-anti-B1 (anti-CD20) antibody and 8 chemotherapeutic agents using 2 human CD20-expressing lymphoma cell lines and 2 corroborative assays, the thiazolyl tetrazolium bromide (MTT) and the Trypan blue dye exclusion assays. ID(50) isobolographic and dose modification factor (DMF) analyses were used to classify interactions between the (131)I-anti-B1 antibody and the chemotherapeutic agents as supra-additive (synergistic), additive or sub-additive. Cytarabine and fludarabine were markedly supra-additive when combined with the radioimmunoconjugate, with the combination enhancing cytotoxicity 3. 5- to 5.2-fold over the level expected by simple addition of the 2 agents (DMFs 3.5-5.2). Etoposide, doxorubicin and SN-38 were moderately supra-additive (DMFs 2.0-2.8). Cisplatin and 4-hydroxycyclophosphamide exhibited merely additive cytotoxicity (DMFs 1.0-1.1). Thus, combination regimens containing (131)I-labeled anti-CD20 antibodies and nucleoside analogs or topoisomerase inhibitors appear particularly attractive for future clinical trials.
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PMID:Synergistic cytotoxicity of iodine-131-anti-CD20 monoclonal antibodies and chemotherapy for treatment of B-cell lymphomas. 1058 92

We designed a phase I trial to assess the feasibility of the combination of topotecan, Ara-C, cisplatin and solumedrol (TOPOSHAP) in patients with relapsed or primary refractory lymphomas. We included 9 patients with measurable non-Hodgkin's (n = 8) and Hodgkin's (n = 1) lymphomas. Level 1 consisted of topotecan 1.0 mg/m(2)/day, i.v., given on days 1-3, cisplatin 25 mg/m(2)/day, i.v., on days 1-3, Ara-C 500 mg/m(2), i.v., on day 4, methylprednisolone 250 mg, i.v., on days 1-4. The regimen was repeated every 3-4 weeks. The maximum tolerated dose was already reached at level 1. G-CSF was added systematically after the 5th patient was included. The most significant toxicity in this trial was hematologic (all had neutropenia WHO grade 4 and 7 had grade 4 thrombocytopenia). Three patients had neutropenic fever. We observed two instances of WHO grade 3 and one of grade 4 diarrhea. Two patients achieved a complete response and 6 a partial response. We conclude that TOPOSHAP with G-CSF support is feasible and should be further studied in phase II studies.
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PMID:Topotecan, Ara-C, cisplatin and prednisolone (TOPOSHAP) for patients with refractory and relapsing lymphomas: results of a phase I trial. 1534 92


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