Clinical therapy of patients contaminated with Polonium or Plutonium

: Although most of the harmful radionuclides are of anthropogenic origin and released from military or industrial processes, radioactive substances also occur naturally in the environment, e.g. uranium. Low standards of nuclear facilities can lead to contamination of employees with radionuclides due to inhalation of gases or dust, or contamination of skin or wounds. Various sources for radionuclide exposure may represent concerns for radioactive polonium or plutonium exposure, for instance terrorist actions on the infrastructure such as on drinking water basins. Early health effects after extensive radiation exposure may be vomiting, headaches, and fatigue, followed by bone marrow depression, fever, and diarrhea. The main purpose of radionuclide mobilization is to minimize the radiation dose. Since some of the important radionuclides such as polonium and plutonium have very long biological half-times after their deposition in bone, liver or kidneys, rapid initiation of chelation treatment is usually imperative after a contamination event. The antidote DMPS (dimercaptopropanesulfonate is considered the drug of choice for polonium decorporation. DTPA (diethylenetriamine pentaacetate) is a potent chelator especially approved for radionuclide mobilization, including polonium and other actinides. Other chelators and drugs are under investigation as potential chelators of transuranic elements.

5-Fluorouracil toxicosis in cats and dogs

5-Fluorouracil is an antineoplastic drug with a narrow therapeutic window. Pets are commonly exposed to the cream used for pre-malignant and malignant skin lesions in humans. 5-Fluorouracil poisoning is characterised by severe gastrointestinal (vomiting; diarrhoea; and gastrointestinal ulceration and haemorrhage) and neurological effects (ataxia, tremors and convulsions), and from 4–7 days bone marrow depression. Progression of signs can be rapid and control of neurological effects can be refractory to treatment. There is no specific antidote suitable for companion animals with 5-fluorouracil toxicosis, and aggressive supportive management is required. Filgrastim (a human granulocyte colony stimulating factor) can be used in the management of severe bone marrow depression, but prognosis is generally poor in dogs and cats with pronounced signs from 5-fluorouracil poisoning.

Dasatinib Drug Use Results Surveys For All Cases As Nationwide Real World Data

Introduction Dasatinib is a BCR-ABL kinase inhibitor that was approved in Japan in January 2009 for the treatment of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This study was aimed to acquire the background information on the patients treated with dasatinib and early data related to safety and efficacy, which would provide important information to ensure the appropriate use of dasatinib. Methods We conducted the nation-wide surveillance for all the patients who used dasatinib for 3 years after starting this medicine. The target number of patients was 800. The principal aims of the survey were to identify: (1) unknown adverse drug reactions, (2) the circumstances under which adverse drug reactions occur in real-world use of the drug, and (3) the factors that may affect safety and efficacy. Especially, we focused on the circumstances of development and incidences of bone marrow depression/cytopenia, hemorrhage, fluid retention, cardiovascular events and abnormal electrocardiogram (QT prolongation), hepatobiliary disorders, and interstitial lung diseases. Results This survey included 903 evaluable subjects for whom survey sheets have been returned to date, June 27, 2012. The composition of the registered cases was: chronic-phase CML 375, accelerated-phase CML 80, blastic-phase CML 133, Ph+ ALL 312, and others 3. Median age was 62 years (range, 7-92) in the chronic-phase CML group, 63.5 years (range, 9-84) in the accelerated-phase group, 63 years (range, 18-86) in the blastic-phase CML group, and 60 years (range, 5-92) in the Ph+ ALL group. 879 patients were previously treated with imatinib. The proportion of imatinib resistant to imatinib intolerant (resistant/ intolerant) in chronic-phase CML was 57.6%/42.4%, in accelerated-phase CML was 84.0%/16.0%, in blastic-phase CML was 78.4%/21.6%, and in Ph+ ALL was 65.1%/34.9%. The median treatment duration (days) was 414 in the chronic-phase CML group, 303.5 in the accelerated-phase CML group, 81 in the blastic-phase CML group, and 96.5 in the Ph+ ALL group. The frequent adverse drug reactions (10% or more) were thrombocytopenia 45.7%, anemia 36.7%, leucopenia 30.7%, pleural effusion 28.0%, and neutropenia 23.8% (all grades). The incidence of bone marrow depression/cytopenia was 56.1%, hemorrhage 10.7%, fluid retention 37.1%, cardiovascular events and abnormal electrocardiogram 4.5%, hepatobiliary disorders 20.4%, and interstitial lung diseases 3.5%. The incidences of bone marrow depression/cytopenia, hemorrhage, and fluid retention in chronic-phase CML were 49.6%, 5.9%, and 28.8%, respectively, and tended to be lower than in the other phases (accelerated phase and blastic phase CML and Ph+ ALL). Additionally, we will report the intervals before the onset of adverse drug reactions, the circumstances of continuation of administration, and factors that appear to affect safety or efficacy based on the latest data update. Conclusions The information in this all-case drug use results survey will be useful to ensure the appropriate use of dasatinib in real-world patients. Disclosures: Kurokawa: Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding. Nishizawa:Bristol-Myers K.K.: Employment. Tetsuka:Bristol-Myers K.K.: Employment. Meiji:Bristol-Myers K.K.: Employment. Hiroshi:Bristol-Myers K.K.: Employment.

Retreatment with pemetrexed-based chemotherapy in advanced nonsquamous NSCLC patients.

e19061^ Background: Retreatment of pemetrexed based chemotherapy (PBC) has been reported in MPM previously, but it is not investigated in non-squamous NSCLC (NS-NSCLC). Methods: We retrospectively enrolled 26 advanced NS-NSCLC patients who had received retreatment of PBC when their response to initial PBC were PR or SD. Chemotherapy regimens administered as retreatment were single pemetrexed (500 mg/m2every 3 weeks) or pemetrexed with a platinum. Response was evaluated according to RECIST. Toxicity was evaluated according to NCI-CTC version 3.0. PFS and OS were computed by Kaplan-Meier. Statistical analyses were performed with SPSS13.0. Results: In retreatment, most adverse effects (AE) were tolerable but doublet regimen was associated with higher AE including bone marrow depression and fatigue. In patients who received retreatment of PBC, objective response rate (ORR) and disease control rate (DCR) was 12% (3/26) and 73% (19/26) respectively. Patient with PFS≥10 months in initial PBC therapy would have a longer PFS in retreatment comparing with those PFS <10 months (6.0 vs 3.1 month, p = 0.004); patients with therapy-free interval (TFI) ≥6 months after initial PBC therapy also have a longer PFS in retreatment comparing with those interval <6 months (7.0 vs 3.0 month, p = 0.001). The OS also tend to be longer but not reach statistic significance. The response of first round PBC therapy (PR vs. SD) was not a factor affecting the PFS in retreatment. Conclusions: Patients with PFS over 10 months or TFI over 6 months after first round of PBC could benefit from retreatment of PBC.

Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients.

Abstract 4111 Objective Biphenotypic acute leukemia (BAL) involves both myeloid and lymphoid cells, and there is lack of uniformity in treatment at present. Optimal approach for therapy of BAL is unknown, and BAL usually becomes refractory to conventional chemotherapy. It was found that CAG regimen [low-dose cytosine arabinoside (Ara-C) plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor (G-CSF)] is effective for both myeloid leukemia and refractory acute lymphoblastic leukemia. To explore the efficiency of CAG regimen for refractory BAL, 12 BAL patients who were failed to daunorubicin/mitoxantrone, cytosine arabinoside, vincristine, prednisone (D/MAOP) regimen, were treated by CAG. 8 were males and 4 was female, with ages ranging from 20 to 43 years (median=34 years). Immunophenotype of B lymphoid lineage/myeloid lineage showed in 8 patients, and T lymphoid lineage/myeloid lineage showed in 4 patients. The patients whose blast cells did not decrease 50% after induction regimen with lymphoid and/or myeloid drugs were defined as refractory cases. Methods 12 refractory BAL patients were treated by CAG regimen (cytosine arabinoside 10 mg/m2 subcutaneously every 12 hours, day 1-14; aclarubicin 5-7 mg/m2 intravenously daily, day 1-8; and concurrent use of granulocyte colony-stimulating factor 200μg·m-2·d-1 subcutaneously) from November 2002 to April 2009. The efficacy of the regimen was evaluated by response rate, and the side-effects was also measured. Results The major chemotherapy toxicity was bone marrow depression, mainly showing as pancytopenia. Median duration of absolute neutrophil count (ANC)<0.50×109/L and of platelet (PLT) count<20×109/L was 13 (range, 1-17) days and 1 day (range, 0-5 days), respectively. Median transfusion of red cells and PLT was 4 (range, 1.5-12) U and 20 (range, 0-40) U, respectively. Besides bone marrow depression, other side-effects such as infection, bleeding, nausea and vomiting also occurred during therapy. According to chemotherapy toxicity assessment of WHO, there were 7 patients confronting infection, among whom only 2 patient occurred III-‡W infection. No serious nausea vomiting or hepatic function damage happened. Disclosures: No relevant conflicts of interest to declare.