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At least 937 records · Page 52Linked to original sources
PubMed1999

Yttrium-90 DOTATOC: first clinical results.

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity). Of 44 patients with advanced somatostatin receptor-positive tumours of different histology, 29 could be included in the study. The 15 patients who were excluded from the study protocol were assigned to our institution for purely compassionate reasons. The 29 patients who were included received four or more single doses of (90)Y-DOTATOC with ascending activity at intervals of approximately 6 weeks (cumulative dose 6120+/-1347 MBq/m(2)) with the aim of performing an intra-patient dose escalation study. In total, 127 single treatments were given. In eight of these 127 single treatments, total doses of > or = 3700 MBq were administered. In an effort to prevent renal toxicity, two patients received Hartmann-Hepa 8% solution during all therapy cycles, while 13 patients did so during some but not all therapy cycles; in 14 patients no solution was administered during the therapy cycles. The treatment was monitored by computed tomography and indium-111 DOTATOC scintigraphy. Blood parameters were controlled weekly, while tumour markers and liver enzymes were controlled 6-weekly. Of the 29 patients, 24 patients showed no severe renal or haematological toxicity (toxicity < or = grade 2 according to the National Cancer Institute grading criteria). These 24 patients received a cumulative dose of < or = 7400 MBq/m(2). Five patients developed renal and/or haematological toxicity. All of these five patients received a cumulative dose of >7400 MBq/m(2) and had received no Hartmann-Hepa 8% solution during the therapy cycles. Four of the five patients developed renal toxicity; two of these patients showed stable renal insufficiency and two require haemodialysis. Two of the five patients exhibited anaemia (both grade 3) and thrombopenia (grade 2 and 4, respectively). To date, 20 of the 29 patients have shown a disease stabilization, two a partial remission, four a reduction of tumour mass <50% and three a progression of tumour growth. (90)Y-DOTATOC could be a powerful and promising new therapeutic agent for anti-cancer treatment - at least in terms of an adjuvant starting point of the disease. However, problems with toxicity have to be solved. Evaluation of the effect of amino acid infusions (e.g. Hartmann-Hepa 8% solution) during (90)Y-DOTATOC treatments with the aim of reducing renal toxicity is ongoing.

Adult↗
PubMed1999

[Rapamycin and CCI-779].

Rapamycin (sirolimus) is a macrolide, related to cyclosporine with immunosuppressive properties and antiproliferative activity in various human tumor cells lines and tumor xenograft models. The cytosolic kinase mTOR which controls the initiation of the translation of messenger RNA is the main known target of rapamycin. During clinical studies, rapamycin given by oral route as immunosuppressant did not show dose-limited toxicity and only asymptomatic thrombopenia and hyperlipemia were observed. In murine models, best antitumoral activity was observed using parental routes. CCI-779, an analog formulated for intravenous use has antitumor activity without significant immunosuppressive property in mice and is currently in phase I trials in man.

Administration, Oral↗
PubMed1976

[Differential diagnosis of chronic myeloic leucemia in infancy (author's transl)].

A 3 months old girl presented with significant enlargement of liver, spleen and lymphnodes, with moderate anemia, thrombopenia and leucocytosis. In the differential count there was a shift to the left and an increase of monocyte-like cells (35%). Differential diagnosis included leucemoid reaction, infectious mononucleosis, myelo-proliferative disorder with a missing C chromosome and chronic myeloid leucemia. Clinical symptoms, cytochemistry and caryotype of bone marrow cells suggested infantile chronic myeloic leucemia and normal ALP index and possibly normal HbF. Treatment with 6-mercaptopurine was followed by partial remission. The therapeutic consequences of exact differential diagnosis are discussed.

Anemia↗
PubMed2000

[Chemotherapy of malignant inoperable gliomas. The association of fotemustine-cisplatine-etoposide as neoadjuvants].

Efficiency of chemotherapy (CT) on non removable HGG has not been proven and neoadjuvant brain irradiation (RT) following biopsy is the standard treatment. We aimed to define whether combination of polychemotherapy and radiotherapy is synergistic in non removable HGG. It has been proven that F, CDDP and VP16 can reach therapeutic levels in brain after intravenous standard dose injections. The aim of this study was to assess that (i) neoadjuvant CT is safe; (ii) feasibility and efficacions of F (100 mg/m2.d1)/CDDP (100 mg/m2.d1-3 TD)/VP16 (75 mg/m2.d1-3) q21-28d regimen; (iii) Delayed RT is not unsafe: RT was performed when tumor progression or toxicity appeared. This study included 16 patients with symptomatic non removable HGG. Two of them had anaplastic gliomas and 14 glioblastomas multiforme. None of them had a prior chemotherapy regimen. Objective response was evaluated with CT scan or MRI during chemotherapy. Toxicity was moderate and mainly hematological (grade III-IV thrombopenia = 10/67 cycles; leukopenia = 13/67). Objective response rates were 5/16 (31 p. 100) (CR = 1; PR = 4; Median duration of response: 20 weeks). Median survival was 55 weeks in the 14 grade IV patients. Three/16 patients are still alived with respectively 22, 30, 40 months survival: These results confirm the neoadjuvant chemotherapy efficacy. It may be a useful tool before RT for non removable HGG.

Adult↗
PubMedDate not supplied

Cisplatin-carboplatin-gemcitabine or ifosfamide-gemcitabine in advanced non-small cell lung carcinoma: two pilot studies.

Gemcitabine has been demonstrated active in non-small cell lung cancer (NSCLC). The objective of this trial was to evaluate the feasibility of combinations of gemcitabine (1 g/m2 dl,8,15) with cisplatin (60 mg/m2 dl) and carboplatin (200 mg/m2 dl) (CCG; n = 12) or ifosfamide (4.5 g/m2 dl) (IG;n = 4) in patients with advanced NSCLC, in order to prepare a phase III randomised trial. Toxicity, mainly haematological, was tolerable. It consisted in neutropenia (IG) and both thrombopenia and neutropenia (CCG). The administration of carboplatin according to the AUC (AUC = 3) resulted in a significant reduction of haematological toxicity. A good number of responses were documented. These acceptable results urged our group to compare these regimens to the combination of cisplatin, carboplatin and if osfamide.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Primary chemotherapy with the Rosen T10 protocol before conservative surgery in limb primitive osteosarcomas: results about 56 cases].

We report the results of a prospective Tunisian study using primary chemotherapy followed by conservative surgery in primitive limb osteosarcoma. From January 1988 to January 1998, 56 patients affected by limb osteosarcoma entered in a prospective study of neoadjuvant chemotherapy with the T10 protocol before surgery with a conservative intent. Initial work-up include: clinical exam with tumor measurements, chest and limb X-rays, limb CT-scan or MRI, chest CT-scan, bone scintigraphy and hematological and renal biological exams. Patients receive pre- and post-operative chemotherapy according to the T10 modified protocol. Fifty-six patients (33 M/23 F) with a mean age of 19 years (8 to 28) are included. Mean clinical and radiological tumor size is around 14 cm. Main histologic type is classic osteosarcoma (50% of cases) and 10 patients (9%) presented with initial metastasis; 42 patients on 56 receive the whole pre-operative protocol. Treatment is well tolerated excluding 18 episodes of mucositis, 29 of leucopenia (< grade 3), 7 of thrombopenia (< grade 3), 4 of cutaneous toxicity, 2 of pulmonary toxicity and 3 of nausea-vomiting. We observe 36% of good histological responders and 64% of bad responders to primary chemotherapy, 27 patients on 49 operated (53%) have a conservative surgery and 18 (47%) a radical surgery. With a median follow-up of 51 months (8 to 128), 29 patients remain alive free of disease (15/17 GR and 14/30 BR), 2 are alive with disease, 2 died by toxicity, 14 died by progressive disease and 9 are lost to follow-up with evolutive disease. Five year disease-free survival is 55% for the 46 non metastatic patients. In univariate analysis, seric alkaline phosphatase level (p = 0.0014) and histological response to chemotherapy (p = 0.0218) are significant factors for prognosis.

Adolescent↗
PubMed2000

[Dose intensified adjuvant chemotherapy in high risk breast carcinoma with 4-9 positive lymph nodes].

OBJECTIVE: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of breast cancer. We evaluated this combination in patients with more than 3 positive lymph nodes in an adjuvant, dose-intensive, sequential therapy in comparison with the standard chemotherapy regimen epirubicin/cyclophosphamide in relation to toxicities. MATERIAL AND METHODS: Since 9/96 127 patients with 4-9/over 9 positive lymph nodes have been recruited from 21 participating centers in an ongoing trial. 67 patients were prospectively randomised for first-line chemotherapy to treatment group A (epirubicin 90 mg/m2-paclitaxel 175 mg/m2; 4 cycles bi-weekly, supported by G-CSF 5 micrograms/kg day 5-13 and 3 sequential cycles of CMF 600/40/600 mg/m2 at 2-weeks interval) and 60 patients to treatment group B (epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2, 4 cycles tri-weekly, and 3 sequential cycles of CMF 600/40/600 mg/m2 at 3-weeks interval). RESULTS: Preliminary safety and toxicity data are evaluable for 679 cycles. Data about response rate and disease-free-survival and overall survival will be delivered later. For the hematological toxicity the main grade 3 and 4 adverse events for A vs. B were: leucopenia 9.8% vs. 8.4%, febrile neutropenia 1.6% vs. 0.8%--anemia (< 5.9 mmol/l), 0.4% vs. 0.2%--thrombopenia 0% vs. 0%. Non-hematological toxicity occurred more frequently in group A (grade 2, 3, 4):--neuropathy 4.4% vs. 0%,--nausea/emesis 27.8% vs. 19.3%,--fatigue 14.6% vs. 3.4% and mucositis 2.8% vs. 0.3%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1975

[Demonstration of gastrointestinal hemorrhages in the acute radiation syndrome].

Increased radioiron excretion with feces following irradiation is a sure indicator of thrombopenia-induced gastrointestinal hemorrhages which are to be regarded as one of the main causes of the acute radiation syndrome or radiation death respectively. We analyzed the daily 59Fe- excretion of whole-body irradiated mice from the 7th to the 16th day after radiation insult, this period being the critical phase in the course of acute radiopathy with a mortality amounting here to about 50% of the irradiated animals (bone-marrow syndrome). On the eleventh day after radiation exposure, 59Fe-excretion of irradiated animals significantly exceeded by more than fivefold that of the controls. If, before radiation exposure, the mice have been treated with the protective agent AET, they survived without exception and, moreover, a significantly reduced 59Fe-excretion was noted too, the control values almost being reached again. By means of the radionuclide 59Fe therefore, ont only statements are possible concerning the functional state of the erythropoietic system, but also troubles of the hemostatic system can be detected, e.g. the pathological transition of blood into the gastrointestinal tract.

Animals↗
PubMed2000

[Treatment of left atrial thrombosis by low-molecular-weight heparin. A preliminary study of 6 cases].

Left atrial thrombosis is a serious complication of atrial fibrillation because of its embolic potential, especially for the cerebral circulation. These thrombi are usually treated by oral anticoagulation. The authors studied the efficacy and tolerance of a low molecular weight heparin. Enoxaparin, in the treatment of this condition. This was a prospective study carried out over a 1 year period. Patient recruitment came from the transoesophageal echocardiography laboratory: of 15 thrombi detected, 6 were treated by ambulatory Enoxaparin therapy. Five of the 6 patients had no signs of left atrial thrombosis after 3 weeks of Enoxaparin therapy. The left atrial thrombus of the 6th patient remained hyperechogenic and had decreased in length from 27 to 24 mm. No cases of bleeding, haematoma, embolism or thrombopenia were observed with this treatment. This preliminary study shows that low molecular weight heparin may be used as an alternative to classical oral anticoagulation for the treatment of left atrial thrombosis.

Aged↗
PubMed2001

[Chemotherapy with cisplatinum, carboplatin and 5FU-folinic acid, followed by concomitant chemo-radiotherapy in unresectable esophageal carcinomas].

UNLABELLED: The best chemotherapeutic regimen for advanced carcinoma of the esophagus remains to be determined. We have evaluated a combination of carboplatin, cisplatin and 5FU modulated by folinic acid. Patients. Twenty-seven patients (median age 57 yrs) with an unresectable carcinoma of the esophagus were included in this trial: 9 patients with a local relapse after surgery, 6 patients with a locally advanced (T4) tumor, and 12 patients with metastasis. Treatment schedule. Initial chemotherapy : carboplatine IV d1, AUC4; 5FU: bolus injection of 400 mg/m2 d1, followed by a continuous infusion of 600 mg/m2/24 h, d1 and d2; folinic acid (200 mg/m2) IV, before the 5FU bolus, d1 and d2; cisplatine 80 mg/m2, d3; on d15 and d16, 5FU and folinic acid were repeated with the same schedule. The second cycle began on d28. Concomitant chemo-radiotherapy with 5FU (1,000 mg/m2 d1 to d3), cisplatine (50 mg/m2 d1 and d2) and external irradiation (20 Gy in 10 fractions from d1 to d12) was then performed, for three cycles (until a total dose of 60 Gy). Results. TOXICITY: neutropenia grade 3-4 (32%), thrombopenia grade 3-4 (18%). More important, a lymphopenia (< 500/mm3) was noted in 12 patients (43%). Accordingly, 4 serious infectious complications were observed, with three toxic deaths. Objective response rate: 44% after initial chemotherapy; 75% after chemoradiotherapy, with 8 complete responses (38%). Median survival was 7.4 months, with a one- and two-year survival of 33% and 17,8%, respectively. Conclusion. This association of cisplatin, carboplatin, and 5FU did not offer a better response rate than the classical 5FU-cisplatinum association. But serious infectious complications occurred during the trial. We do not recommended further evaluation of this biplatinum therapy with 5FU in advanced esophageal carcinomas.

Adult↗
PubMed2001

[Low molecular weight heparin (dalteparin) in treatment of patients with thromboembolism incidents].

UNLABELLED: Low molecular weight heparine (LMWH) is an established treatment for deep venous thrombosis during the initial phase of the illness as well as for prophylaxis of thrombosis. There are only few studies concerning the use of LMWH in the initial treatment of lung embolism. 138 Patients with either deep venous thrombosis at least reaching the vena poplitea and/or lung embolism have been randomised into two groups. One group was treated with unfragmented heparin. The second group received a single dose of 200 I.E./kg body weight/d LMWH (Dalteparin). The results were compared with regard to the recurrence of thrombosis and embolism, bleeding, heparin-induced thrombopenia and mortality. RESULTS: A total of 138 patients were randomised. 13 patients were excluded later. The two groups were comparable regarding age, sex, weight and diagnosis. The average treatment lasted 8.3 (5-26) days in the LMWH-group and 7.4 (4-14) days in the heparine-group. The average hospital stay was 10.4 days in the LMWH-group, and 11.0 days in the heparine-group. The complication rate was 5 (3.1%) (5 events: 3 hemorrhages, 1 reembolism, 1 death) in the LMWH-group and 4 (2.5%) (4 events: 3 bleedings, 1 sepsis of the venous catheter) in the heparine-group. We found no significant outcome difference between the two treatment groups. CONCLUSION: Weight-adapted (200 IE/kg/day) subcutaneous application of Dalteparin once daily in the treatment of patients with deep venous thrombosis or lung embolism is as safe as intravenous treatment with unfragmented heparine.

Aged↗
PubMed2001

[Interferon-alpha and PUVA therapy for mycosis fungoides].

14 patients suffering from early stage mycosis fungoides were treated with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4 patients in stage II a and 6 patients in stage II b/during 3-21 months time course. Interferon alpha 2-a was administered 3 times a week, in escalating dose from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the patients responded well to the treatment. Partial remission was observed after 4-13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9 months of the treatment. Side effects occurred frequently: weight loss, pain, fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the side effects the dose of the interferon was reduced individually, the dose reduction did not cause relapse.

Aged↗
PubMed2001

[Comparison of the effectiveness of idarubicin (Zavedos) and mitoxantrone (Refador) in induction therapy of acute myeloid leukemia in elderly patients (55-75) (a prospective multicenter randomized study conducted 1998-2000].

The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar (3 + 7) in induction treatment of the patients with AML aged 55-75. 31 patients at the age of 55-75 (median 62) were evaluated in the arm with idarubicine and 29 patients at the age of 57-74 (median 64) in the arm with mithoxantrone. Complete haematological remission was achieved in 13 patients (41.9%) in the arm with idarubicine and 15 patients (51.7%) in the arm with mitoxantrone. The medians of overall survival time (OS) and disease free survival time (DFS) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm, respectively. Statistical analysis did not prove any significant difference in the complete remission rates, in the number of deaths during cytopenia, in the OS or DFS, in the duration of hospitalisation, severe neutropenia and thrombopenia, in the number of days with febrile neutropenia, or in the consumption of platelets and erythrocytes transfusion units between both arms. Despite the fact that these results are not statistically significant in favour of any treatment arm, which is probably influenced also by the small number of evaluated patients, more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters. From the point of view of cost-effectiveness, the difference could be observed when considering the price of both intercalating cytostatics. The use of mitoxantrone (Refador, Lachema) is 15x times cheaper per course of treatment than the use of idarubicine (Zavedos, Pharmacia). Autologous peripheral blood stem cells transplantation (APBSC) was carried out only in 4 patients younger than 60. No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group. The results achieved are comparable with those of other trials conducted by various foreign groups. The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed.

Acute Disease↗
PubMed2001

[Effect of thrombopoietin II on exsanguine thrombocytopenia mouse death rate].

OBJECTIVE: To study the effect of thrombopoietin II (TPO II) on the exsanguine thrombocytopenia mouse death rate. METHODS: After the normal peripheral platelet counts were done on the samples obtained from the tail vein of purebred Babl/c mice before experiment, the purified ligand I of TPO II, artificial compound ligand II of TPO II and rhTPO were injected intraperitoneally once a day for 7 days. On d 7 and d 14, platelet counts were performed on 0.5 ml samples obtained from the supra-orbital vein, with the condition of the mouse death monitored daily. RESULTS: On d 7, ligand I of TPO II group platelet counts were higher than that of the negative control group (P < 0.05), while not being significantly different from that of rhTPO group (P > 0.05). On d 14, the platelet counts of two TPO II groups increased significantly as compared with the negative control group (P < 0.01), showing no significant difference from that of rhTPO group (P > 0.05). Moreover, the platelet counts of mice in two TPO II groups and the positive group had shown an increasing tendency in the days following experiment. In addition, mouse death occurred in all groups of mice following their phlebotomy from the supraorbital vein on d 7. But the death rate of negative control group was evidently higher than that of any other groups (P < 0.05). CONCLUSION: TPO II's biological activity obviously increases platelet production, thereby reducing the exsanguine thrombopenia mouse death rate.

Animals↗
PubMed2001

[Nitrullin -- a new original Russian drug of the nitrosomethylurea group].

Hematologic thrombopenia and leukopenia formation limits use of nitrullin as a toxic hazard. The drug showed moderate effect in treating inoperable non-small cell cancer of the lung and satisfactory end results. The treatment had marked symptomatic effect in patients with this cancer and, as a consequence, improved the quality of life. Nutrullin had immuno-modulating effect. Its application alone or in combination with VPN showed good results in the management of small-cell cancer of the lung.

Adenocarcinoma↗
PubMed2002

[Results up to now of administration of STI-571 (Glivec) in recurrence after allogenic and autologous stem cell transplantation in chronic myeloid leukemia].

BACKGROUND: Gleevec (STI-571) is s selective inhibitor of the bcr/abl tyrosine kinase. Recent phase I and phase II studies in patients with bcr/abl positive CML and ALL showed a low rate of grade III/IV toxicity and good clinical efficacy. This report describes the preliminary results in patients relapsing post autologous or allogeneic peripheral blood stem cell transplantation. The focus of this analysis will include toxicity, feasibility and clinical efficacy. THERAPY AND RESULTS: 18 of 18 patients with cytogenetic and/or hematologic relapse in chronic phase CML post autologous stem cell transplantation achieved a complete hematologic remission upon therapy with Gleevec. The cytogenetic response rate was 75% with a complete cytogenetic response rate of 50%. After allogeneic stem cell transplantation, patients in cytogenetic or hematologic relapse also experienced high hematologic and cytogenetic response rates upon therapy with Gleevec. In these patients, Gleevec was shown to induce mixed chimerism. Overall, Gleevec was well tolerated after autologous and allogeneic stem cell transplantation. Most common side effects were mild to moderate gastrointestinal discomfort and edema. No symptoms of chronic extensive or > grade I acute GvHD could be observed. Hematologic toxicity was dependent on stage of disease. Grade III/IV granulocytopenia and/or thrombopenia could be observed in 50% of patients with transformed phases of CML. Management of these patients required frequent controls of peripheral blood counts and transfusion of blood products. CONCLUSION: These results show a new approach in treatment of patients with Philadelphia-chromosome-positive leukemia relapsing post autologous or allogeneic stem cell transplantation. Gleevec is able to induce mixed chimerism without induction of severe GvHD. The data suggest that early start of STI-571 therapy in MRD-positive patients is a promising approach. Recently, a multicenter phase II study to evaluate the toxicity and efficacy of Gleevec in CML patients with minimal residual disease post allogeneic transplantation was started.

Adolescent↗
PubMed1979

A new case of IgE myeloma (Des) ending with renal failure.

A new case of IgE myeloma (Des), a woman aged 55, is presented. The monoclonal Ig was identified as an IgE of the kappa type. The case history is detailed. Bone lesions were absent; there were up to 12% plasma cells in the peripheral blood; therapy with cytostatic drugs could not be applied because of leuco- and thrombopenia. The patient died of renal failure after having been maintained one year on steroids and transfusions. A comparison between several clinical and laboratory data of this new case, the twelfth to the author's knowledge, and those of the preceding ones, is also given.

Acute Kidney Injury↗
PubMed2002

[Intermittent thrombocytopenia as a manifestation of Von Willebrand's disease].

A 38-year-old man with Von Willebrand's disease type 2 came to us for treatment advice in relation to a trip abroad, and also a 53-year-old woman with bleeding treated as idiopathic thrombocytopenic purpura (ITP). In the man, a trial dose of desmopressin led to severe thrombopenia, and in the woman, treatments, such as splenectomy and prednisone in the past, had been ineffective. In both patients further investigations led to the diagnosis 'Von Willebrand-disease type 2B'. Despite the fact that Von Willebrand's disease type 2B has distinctive laboratory characteristics, such as thrombocytopenia, a positive Ristocetin Induced Platelet Agglutination (RIPA) test at a low ristocetin concentration, and an abnormal multimer pattern, some cases have incomplete or atypical presentations which can be misleading for the diagnosis. A wrong diagnosis can lead to ineffective and potentially dangerous therapeutic interventions. Molecular genetic analysis of type 2B mutations is simple and can help in making the correct diagnosis in cases of familial thrombocytopenia or for a further characterisation of Von Willebrand type 2.

Adult↗