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

Brequinar (DUP 785, NSC 368390) is a 4-quinoline carboxylic acid derivative with broad spectrum antitumour activity in experimental models that acts as an antimetabolite by specific inhibition of de novo pyrimidine synthesis. We performed a phase I study of brequinar administered as a 10 min intravenous (i.v.) infusion for 5 consecutive days, every 4 weeks. 67 evaluable patients were entered in this study and a total of 130 courses were administered at doses ranging from 2 to 350 mg/m2. The dose-limiting toxicity was myelosuppression with predominant thrombocytopenia. Myelosuppression was dose-related and non-cumulative, with considerable interpatient variability depending on haematological risk factors. The maximum tolerated dose of brequinar was 210 mg/m2/day in poor risk patients whereas patients with good risk haematological profile tolerated higher doses (up to 350 mg/m2/day). Other non-limiting toxicities included nausea and vomiting, mucositis and skin reactions. Brequinar plasma pharmacokinetic profiles were biphasic with alpha half-life ranging from 0.1 to 0.7 h, and beta half-life ranging from 1.5 to 8.2 h. Increase in brequinar area under the plasma concentration versus time curves (AUC) was nonlinear. Day 5 brequinar pharmacokinetics obtained in 21 patients indicated a significant increase in AUC (47%) and half-life beta (133%) compared to day 1 pharmacokinetics in the same patient. Brequinar plasma AUC and the per cent change in platelet count at nadir were correlated (P < 0.001). Although no objective response was observed in this study, one minor response was noted in cervical lymph nodes of a Hodgkin's disease patient.
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PMID:Phase I and pharmacokinetic study of brequinar (DUP 785; NSC 368390) in cancer patients. 849 53

We conducted an evaluation of the usefulness of antiemetics (5-Hydroxy-tryptamine 3 receptor antagonism, 5HT3RA) combined with diazepam for delayed nausea and vomiting due to anticancer agents in 17 patients with various malignancies (such as lung Ca, breast Ca, esophagus Ca, gastric Ca, colon Ca, and non Hodgkin's disease) for whom chemotherapy was performed with different regimens in the Dept. of Oncologic Chemotherapy, People's Hospital, Beijing Medical University. Antiemetics (5HT3RA) combined with diazepam were given only to cases that had symptoms of nausea and vomiting induced by anticancer agents in the 1st course and invalidity with antiemetics (5HT3RA) alone in this study. Antiemetic (5HT3RA) agents + Dexamethasone were dosed before chemotherapy and also diazepam 5 mg orally after 24 hours (namely, when nausea was observed). Nausea was reduced and vomiting decreased after the antiemetic treatment with 5HT3RA + Dexamethasone and diazepam. These results indicated that 5HT3RA and diazepam combination therapies were more effective than 5HT3 RA + Dexamethasone alone for delayed nausea and vomiting. Further, the antiemetics had characters that a short adminiter time, few times and a take not over dose. The only side effect related to this antiemetic therapy was light somnolence. Antiemetics combined with diazepam might be a useful therapy against delayed nausea and vomiting induced by anticancer agents.
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PMID:[Effect of diazepam on delayed nausea and vomiting caused by anticancer agents]. 949 33

We performed a clinical phase II study of KRN8602, a new anthracycline derivative, for relapsed or recurrent malignant lymphoma. KRN8602 was given at doses of 12-15 mg/m2 for 3 consecutive days, repeating every 3-4 weeks. Among 44 patients entered into the study, 36 were evaluable for safety, and 35 were evaluable for efficacy. The response rate was 18.2% (6PR/33) for non-Hodgkin's lymphoma and 0% (0/2) for Hodgkin's disease. Major toxicities were bone marrow suppression and gastrointestinal toxicity. Leukopenia was observed in 77.8%, thrombocytopenia in 44.4%, hemoglobin decrease in 44.4%, nausea and vomiting in 94.4% and anorexia in 80.6%. However, all toxicities were clinically manageable.
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PMID:[Phase II study of KRN8602 (MX2) for malignant lymphoma]. 964 14

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.
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PMID:A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors. 974 May 42

Idarubicin is the first anthracycline that can be administered orally facilitating antineoplastic chemotherapy at an improved quality of life. In different studies idarubicin has proved clinical effectiveness in patients with advanced low grade non Hodgkin's lymphoma. We performed a phase II study in 19 patients with untreated and pretreated B-CLL of Binet stage A-C. Idarubucin was administered orally at a dose of 15 mg/m2 over 3 days every 4 weeks. Of 19 evaluable patients (m:f, 16:3, median age 64 years, range 41-80 years) 7 were previously untreated while 12 patients had received prior therapy with fludarabine, chlorambucil or similar non-anthracycline containing regimens. 12 pts had Binet stage C, 5 Binet stage B and 2 Binet stage A. Five patients achieved a partial remission (26%), 5 patients had stable disease (26%) and 9 patients showed progressive disease (47%), resulting in an overall response of 26% (5/19). There was no correlation of response rate with Binet stages or previous treatment regimens. Treatment associated side effects consisted predominantly of mild nausea and vomiting (26%) as well as minor infections (21%) and diarrhoea (16%). These data demonstrate that oral idarubicin as a single agent is well tolerated but of limited effectiveness in B-CLL. Further studies are needed to assess different doses and schedules of oral idarubucin and to test it in combination with other chemotherapeutic agents.
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PMID:Multicenter phase II study of oral idarubicin in treated and untreated patients with B-chronic lymphocytic leukemia. 1072 82

Primary splenic lymphoma is uncommon, constituting only 1-2% of all patients with malignant lymphoma. Despite the rarity of this malignancy, the number of primary splenic lymphoma being reported has increased due to its ambiguous definition used in the literature. We describe a case of a 41-year-old man with chronic hepatitis C virus infection presenting abdominal discomfort in the upper left quadrant, weakness, nausea and vomiting. Abdominal computed tomography revealed nodules in the congested splenic parenchyma. Splenectomy was performed and an analysis of the spleen diagnosed B-cell non-Hodgkin's lymphoma. Biopsy of the liver showed evidence of hepatitis C virus. Bone marrow biopsy revealed no tumor infiltration. The patient has been followed to date, has progressed quite well and remains essentially asymptomatic. Recently, an etiologically important role has been suggested for hepatitis C virus infection in the development of B-cell non Hodgkin's lymphoma. Lymphotropism of hepatitis C virus may play a pathological role in the development of non Hodgkin's lymphoma. It is important to add lymphoma to the list of differential diagnosis of extrahepatic disorders in patients with chronic hepatitis C virus infection.
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PMID:Primary splenic lymphoma in patient with hepatitis C virus infection: case report and review of the literature. 1132 5

High and intermediate grade non-Hodgkin's lymphomas (NHL) require treatments with aggressive chemotherapy schedules. However, low grade NHLs display a low chemoresponsiveness and patients aged >65 years often do not tolerate anthracycline and corticosteroid-containing chemotherapy regimens. Therapeutic options in this subset of patients are watchful waiting, oral alkylating agents, purine nucleoside analogues, combination chemotherapy, interferon and monoclonal antibodies. The approval of rituximab, an unconjugated chimeric antibody against the CD20 antigen for the treatment of B-cell NHL marked a milestone in the development of antibody treatment. Moreover, promising results have also been found with oxaliplatin in patients with NHL and reversible, cumulative, peripheral sensory neuropathy is the principle dose-limiting factor of oxaliplatin therapy. On the basis of these considerations we have performed a feasibility study in NHL in patients aged >65 years using as schedule: 130 mg/m2 oxaliplatin every 21 days and 375 mg/m2 rituximab weekly. We have enrolled 8 patients, 2 males and 6 females (mean age 69.2+/-3.1 years; median, 67 years) affected by intermediate or high grade stage III/IV NHL. Six patients have cardiac abnormalities (myocardial function between 45 and 50%) and 1 increase of transaminasemia due to active chronic hepatitis. All the patients included in the study were treated for at least 3 cycles and 31 cycles were completed. We have recorded grade I/II (CTC) neurotoxicity in 30%, grade I anemia in 25% and grade I neutropenia in 20% of the patients. No infusional reactions, liver or renal toxicity neither nausea and/or vomiting were recorded. One complete response, 3 partial response and 3 minimal response were obtained at 11 months of median time follow-up. These results demonstrate the feasibility of this schedule which offers a suitable alternative regimen to treat elderly patients with NHL and shows a good efficacy and an acceptable toxicity profile.
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PMID:Oxaliplatin/rituximab combination in the treatment of intermediate-low grade non-Hodgkin's lymphoma of elderly patients. 1520 74

The aim of this study was to investigate thiotepa (TT) and fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplant in patients not eligible for a standard myeloablative regimen due to comorbidities and/or poor performance status. TT was given at a dose of 10 mg/kg over 2 days and Fluda at 125 mg/m(2) over 5 days. In all, 21 patients (14 male, seven female; 10 acute leukaemia, eight myelodysplastic syndrome, two non-Hodgkin's lymphoma, one Hodgkin's disease) were treated. The median age was 51 years (range 30-55 years). All patients achieved full donor-type chimaerism. Adverse events included mild nausea and vomiting in two patients and a slight increase of serum amylase in three. A total of 13 patients received RBC transfusions (median 6 U, range 1-23), and all received platelets (median 4 U, range 1-27). Four patients died of nonrelapse causes and five of relapse. The 1-year probabilities of transplant-related mortality and relapse were 19 and 29%, respectively. In total, 12 patients remain in complete remission (median follow-up: 786 days). The 3-year overall survival probability was 58%. We conclude that this regimen is feasible and well tolerated.
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PMID:Reduced-intensity conditioning regimen with thiotepa and fludarabine followed by allogeneic blood stem cell transplantation in haematological malignancies. 1551 36

Surgical resection of primary colonic lymphoma can be an important therapeutic tool. We performed a nonrandomized retrospective descriptive study at the University hospital tertiary care center. From January 1990 to June 2002, a total of 15 patients with primary colonic lymphoma were identified from the tumor registry at University of Alabama at Birmingham and retrospectively reviewed under Institutional Review Board approved protocol. Demographic data, clinical features, treatment method (surgery and/or chemotherapy), recurrence rate, and survival were analyzed. The results are presented as mean +/- standard deviation or median and range. Differences in survival were evaluated by the log-rank test and the interval of disease-free survival was calculated using the Kaplan-Meier method. A P value of <0.05 was considered statistically significant. Main outcome measures included surgical results, morbidity, mortality, and recurrence rate. Mean age was 51.5 years (standard deviation 16.4), 33 per cent were male and 67 per cent were female. Presenting symptoms were diarrhea (53.5%), lower gastrointestinal bleeding (13.3%), and nausea and vomiting (46.7%) secondary to low-grade obstruction. Concomitant colorectal disease was present in one patient with ulcerative colitis. Preoperative diagnosis of lymphoma was made in 13 patients (87%) with colonoscopy and biopsy. CT scan was performed in all patients; and none had radiographic evidence of systemic extension. Only one patient had a history of lymphoproliferative disease and exposure to radiation. The most common disease location was the cecum (60%), followed by the right colon (27%), and the sigmoid colon (13%). The mean lactic dehydrogenase (LDH) value was 214.9 u/L (range 129-309). Thirty-three per cent of the patients had an LDH value that was above the upper normal limit. LDH returned to normal after treatment in all patients. Operations performed consisted of right hemicolectomy (13), total proctocolectomy with ileal J J-pouch (1), and sigmoid colectomy (1). Eighty-seven per cent had negative margins at the time of operation. Twelve patients received postoperative chemotherapy (80%). According to the clinical classification of primary non-Hodgkin lymphoma (NHL) of the gastrointestinal tract (Lugano, 1993) all patients corresponded to stage IE. Mean hospital stay was 6.4 days (range 3-26). There was no surgical mortality and the morbidity rate was 20 per cent (3 patients). One patient had a systemic recurrence (7%) approximately 4 months after surgical resection. Mean follow-up was 31 months (median 2-73). Surgical resection of localized, primary colonic lymphoma provides excellent local disease control and should be considered a primary treatment option. The role of chemotherapy remains controversial depending on the grade, stage, and extension of residual disease.
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PMID:Primary colonic lymphoma. 1837 84

This study assessed the efficacy and safety of dolasetron compared with ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy followed by peripheral blood stem cell support. Twenty centers randomized 197 patients to receive dolasetron 100 mg intravenously (I.V.) followed 8-12 hours later by a single oral dose of dolasetron 100 mg or ondansetron 32 mg I.V., followed 8-12 hours later by a single oral dose of ondansetron 8 mg during high-dose chemotherapy (HDC) regimens for breast cancer (n = 96; 48.7%), non-Hodgkin's lymphoma (n = 83; 42.1%), or Hodgkin's disease (n = 18; 9.1%). All patients received a daily I.V. bolus of dexamethasone 10 mg with study antiemetic agents and a continuous infusion of diphenhydramine, lorazepam, and dexamethasone (ie, BAD pump) throughout the course of the study, with patient-controlled on-demand bolus doses as needed. After completing a daily diary of emetic episodes and rescue medication use, 164 of 197 patients were evaluable. Total plus complete responses (no emesis, no nausea, no rescue) over the entire study period were achieved in 45.7% and 46.9% of patients on the dolasetron and ondansetron arms, respectively. Dolasetron and ondansetron were well-tolerated. This study demonstrates that dolasetron and ondansetron are equally safe and effective in the prevention of nausea and vomiting associated with HDC (P = 0.955).
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PMID:A randomized, multicenter, open-label comparison of the antiemetic efficacy of dolasetron versus ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy. 1862 98


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