Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vindesine, a newer vinca alkaloid derivative, underwent a phase I clinical evaluation in 68 humans with advanced, refractory malignancies. Patients received single total doses ranging from 2 to 12.5 mg, repeated every 1-2 weeks. Dose-limiting myelosuppressive, gastrointestinal, and neurologic toxic effects were observed at higher doses. They consisted predominantly of neutropenia, constipation leading, on occasion, to paralytic ileus, and peripheral neuropathy. Total doses of 7.5-10 mg (equivalent to 4-5 mg/m2), repeated every 2 weeks, well-tolerated. There were two partial remissions in patients with acute leukemia and prior vincristine therapy, two minor responses in patients with renal cell carcinoma, one minor response in a patient with squamous cell carcinoma of the esophagus, and one minor response in a patient with squamous cell carcinoma of the lung. Vindesine is well-tolerated by man, although it shares some of the toxic manifestations of vinblastine and vincristine. Its efficacy in some patients who were no longer responsive to vincristine therapy suggests a lack of clinical cross-resistance between these compounds.
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PMID:Initial clinical studies of vindesine. 626 96

Fifteen patients with advanced squamous cell cancer of the head and neck received weekly vindesine at doses of 3 mg/m2. No patient had received prior chemotherapy, though all had received either radiotherapy or radiotherapy and surgery. Fourteen patients were evaluable for response. Two patients had documented partial remissions. Dose-limiting neutropenia was the primary toxic effect observed. It was frequent and occasionally life-threatening. Vindesine has minor but real activity in this group of patients with advanced head and neck cancer who have not received prior chemotherapy.
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PMID:Phase II trial of vindesine in patients with squamous cell cancer of the head and neck. 673 43

A phase II study of vindesine in 41 evaluable patients demonstrated the drug to be active in heavily pretreated patients with breast cancer, non-Hodgkin's lymphoma, and other tumors. There were two partial responses in 11 patients with breast cancer (18%) and five partial responses and one complete response in 11 patients with non-Hodgkin's lymphoma (40%). Other responses were seen in small cell carcinoma of the lung, ovarian carcinoma, and Hodgkin's disease. Prior vinca exposure did not adversely affect the response rate. Neutropenia was dose-limiting. Neurotoxic effects occurred in 10% of the patients. A high incidence of local tissue reactions at the injection site (27%) could be reduced by a careful administration technique. Vindesine should be studied further in combination with other agents.
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PMID:Phase II trial of vindesine in the treatment of lymphomas, breast cancer, and other solid tumors. 744 18

We have found transient circulating neutropenia and pulmonary sequestration of neutrophils after the intravenous injection of vindesine, a microtubule disruptor. Experiment 1 Ten patients with lung cancer were given a bolus intravenous injection of 3 mg.m-2 vindesine (Fildesine(r)). In all patients, total leukocyte and neutrophil counts in the venous blood fell to 65% and 47% of baseline values respectively within 30 min, and returned to baseline values within 6 h. In contrast, the lymphocyte count was stable. Experiment 2 Male Wistar rats were given saline or 0.08 mg.kg-1 vindesine intravenously and were sacrificed after 30 min. Vindesine produced a 58% reduction in the neutrophil count in the systemic circulation and a threefold increase in the neutrophil/erythrocyte ratio in the pulmonary microvasculature. Experiment 3 We studied the effects of vindesine in vitro on neutrophils and lymphocytes isolated from the venous blood of healthy volunteers. Vindesine (10(-5)-10(-8) mol.l-1) reduced neutrophil deformability (filterability) and induced neutrophil polarization, with reversibility of both effects after washout. These effects of vindesine were completely inhibited by cytochalasin B, an actin filament disrupter. Vindesine did not stimulate the neutrophil functions of adherence to polystyrene tubes, chemotaxis, or superoxide anion generation. The filterability and morphology of lymphocytes were not altered by vindesine. Thus, we conclude that a bolus injection of vindesine produces pulmonary sequestration of neutrophils, which produces circulatory neutropenia, and that it is primarily mediated by a decrease in neutrophil deformability that occurs without activation of the cells.
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PMID:Transient neutropenia after intravenous injection of vindesine in patients with lung cancer. 798 20

Hematological and clinical data of 14 children with neuroblastoma treated according to the German neuroblastoma therapy study NB 90 were analyzed. Therapy included 4 or 8 intensive therapy elements N1 (Etoposide 125 mg/m2 day 1-4, Vindesine 3 mg/m2 day 1, Cisplatin 40 mg/m2 day 1-4) and N2 (Vincristine 1.5 mg/m2 day 1 + 8, Dacarbazine 200 mg/m2 day 1-5, Ifosfamide 1500 mg/ m2 day 1-5, Doxorubicin 30 mg/m2 day 6 + 7) in alternating order. The hematological recovery was studied after 86 therapy elements N1/N2. G-CSF had been given in 23 therapy courses, while no cytokine was administered in 63 therapy courses. Mobilization of CD34+ cells was studied in 13 therapy courses with G-CSF. Severe myelosuppression with an absolute neutrophil count < 500/microL was noted 2-4 weeks after each therapy element. The use of G-CSF did not prevent, but shortened neutropenia. There was no difference in the number of infections nor time delay of therapy between the courses with or without G-CSF. In 11 therapy courses G-CSF was started on the day following the last chemotherapy dose (N1: day 5; N2: day 9). In 12 therapy courses G-CSF was given delayed, starting day 12 after the initiation of therapy. Kinetics of granulocyte recovery was similar in the early or delayed application of G-CSF. Neutrophil recovery after the therapy element N1 was earlier and faster compared to that of therapy element N2. The more rapid rise of the neutrophils after the N1 element was accompanied by an effective mobilization of CD34+ cells. Taking into account the limitations of this retrospective study, the data may help to optimize the application of G-CSF in a very intensive therapy study like NB90.
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PMID:[Kinetics of myelopoietic regeneration and mobilization of CD34-positive cells within the scope of the NB90 Neuroblastoma Therapy Study]. 934 Apr 28