Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite effective therapies for non-Hodgkin's lymphoma (NHL), the majority of patients are not cured. Radioimmunotherapy (RIT) has shown good results in preclinical and clinical trials even in patients that are non-responsive to standard chemotherapy. To make RIT more effective, agents such as paclitaxel (Taxol), that can enhance radiation effects, are being tested. Nude mice bearing human Burkitt's lymphoma (Raji) xenografts were treated with: 1) 150 or 200 microCi (5.5 or 7.3 MBq) of 90Y-2IT-BAD-Lym-1 alone, 2) 600 micrograms of Taxol alone, 3) 150 or 200 microCi of 90Y-2IT-BAD-Lym-1 plus 600 micrograms of Taxol given 24 hours after RIT, or 4) no treatment. Tumor size, survival, mouse weight and blood counts were monitored to assess efficacy and toxicity. Survival for mice treated in this 84 day trial was: 71% for 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol, 29% for Taxol alone, 6% for 90Y-2IT-BAD-Lym-1 (200 microCi) alone and 14% in the untreated group. Average tumor volume in the 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol group was reduced by 89 and 99% compared to the RIT alone and Taxol alone groups, respectively. Mice treated with 150 microCi had less toxicity than those treated with 200 microCi of 90Y-2IT-BAD-Lym-1, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RIT plus Taxol) groups were similar to those receiving the same dose of RIT alone. In the Raji tumored nude mouse model, addition of Taxol to 90Y-2IT-BAD-Lym-1, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity.
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PMID:Combined modality radioimmunotherapy with Taxol and 90Y-Lym-1 for Raji lymphoma xenografts. 1085 25

Radioimmunotherapy using radiolabeled monoclonal antibodies against tumor-associated antigens has been efficacious, particularly in the treatment of radiosensitive malignancies such as lymphoma. Antilymphoma monoclonal antibody Lym-1, labeled with copper-67 ((67)Cu), iodine-131 ((131)I), or yttrium-90 ((90)Y), has been effective salvage therapy for patients with non-Hodgkin's lymphoma. Although (131)I has had the dominant role in radioimmunotherapy thus far, several properties of radiometals are preferable. A total of 70 patients with B-lymphocytic non-Hodgkin's lymphoma were studied using (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, or (111)In-2IT-BAD-Lym-1. Because (90)Y does not have good emissions for imaging, indium-111 ((111)In), its analogue, was used as a surrogate to estimate (90)Y-2IT-BAD-Lym-1 pharmacokinetics and radiation dosimetry. Subsets of four patients in each group received (67)Cu- and (131)I-labeled Lym-1 or (111)In- and (131)I-labeled Lym-1, allowing direct comparisons of the radioimmunoconjugates. Sequential blood samples and planar images were used to quantitate radioimmunoconjugate in tissues in order to determine pharmacokinetics and radiation dosimetry. (67)Cu-2IT-BAT-Lym-1 and (90)Y-2IT-BAD-Lym-1 exhibited higher cumulated activity concentrations and radiation absorbed doses per unit of administered radioactivity for tumors than did (131)I-Lym-1. The mean tumor cumulated activity (area under the time-activity curve) concentrations per unit of administered radioactivity for (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 96.89, 33.96, and 43.42 GBq-s/GBq/g, respectively. The mean tumor radiation doses from (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 2.5, 1.0, and 6.6 Gy/GBq, respectively, because (90)Y deposits more radiation per unit of administered radioactivity. Per unit of administered radioactivity, radiation doses from (67)Cu-2IT-BAT-Lym-1 and (131)I-Lym-1 to normal tissues were similar except that the liver received a higher dose from (67)Cu-2IT-BAT-Lym-1 than from (131)I-Lym-1; radiation doses to normal tissues from (90)Y-2IT-BAD-Lym-1 were generally higher. Consequently, the therapeutic indices (ratio of radiation doses to tumor and normal tissues) for (67)Cu-2IT-BAT-Lym-1, and less generally for (90)Y-2IT-BAD-Lym-1, were more favorable when compared to those for (131)I-Lym-1. Data from the matched subsets of patients showed similar therapeutic indices to those for the groups of patients. (67)Cu-2IT-BAT-Lym-1 showed more potential than (131)I-Lym-1 or (90)Y-2IT-BAD-Lym-1 for non-Hodgkin's lymphoma radioimmunotherapy.
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PMID:Are radiometal-labeled antibodies better than iodine-131-labeled antibodies: comparative pharmacokinetics and dosimetry of copper-67-, iodine-131-, and yttrium-90-labeled Lym-1 antibody in patients with non-Hodgkin's lymphoma. 1170 20

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