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  • 1
    ISSN: 1569-8041
    Keywords: BBR3464 ; phase I ; platinum analog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives:To define the maximum tolerated dose (MTD), thetoxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods:Fourteen patients with advanced solid tumorsnot responsive to previous antitumor treatments received BBR 3464 on a daily× 5 schedule every twenty-eighth day. The drug was given as a one-hourinfusion with pre-and post-treatment hydration (500 ml in one hour) and noantiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. Amodified accelerated titration escalation design was used. Total and freeplatinum (Pt) concentrations in plasma and urine were assessed by ICP-MS ondays 1 and 5 of the first cycle. Results:Dose was escalated four times up to 0.17mg/m2/day. Short-lasting neutropenia and diarrhea of late onsetwere dose-limiting and defined the MTD at 0.12 mg/m2. Nausea andvomiting were rare, neither neuro- nor renal toxic effects were observed.BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-lifeof several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 werehigher than on day 1, indicating drug accumulation. Approximately 10%of the equivalent dose of BBR3464 (2.2%–13.4%) wasrecovered in a 24-hour urine collection. Conclusions:The higher than expected incidence of neutropenia andGI toxicity might be related to the prolonged half-life and accumulation oftotal and free Pt after daily administrations. Lack of nephrotoxicity and thelow urinary excretion support the use of the drug without hydration. Thesingle intermittent schedule has been selected for clinical development.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: cisplatin ; head and neck cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Cisplatin is an active drug in head and neck cancer. Paclitaxel seems a promising drug. This article reports a phase II assessment of the combination of the two. Patients and methods: Twenty-three patients were treated with paclitaxel 90 mg/m2 over three hours plus cisplatin 60 mg/m2 every other week. Sixteen patients had locoregional disease and seven had metastatic disease. None of the patients had previously been treated with chemotherapy. Nine patients had had radiotherapy to the target lesions. Results: One patient was not evaluable for response. Partial responses were observed in 32% of evaluable patients. Toxicity included asthenia (56%), neutropenia, peripheral neuropathy, anemia and vomiting. Conclusions: The overall response rate observed in this study does not seem to justify the use of this chemotherapy regimen in the palliative setting.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1619-7089
    Keywords: Key words: Serum Amyloid P Component ; Amyloidosis ; Iodine-131 ; Iododoxorubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid. Iodine-123 has ideal physical characteristics for scintigraphy but is expensive and not widely available. Here we report serial imaging and turnover studies in which we labelled SAP with iodine-131, a cheap alternative isotope which would be expected to yield poorer images but permit more prolonged turnover measurements. Imaging and plasma clearance and whole body retention (WBR) of tracer were studied for up to 7 days in ten patients with proven systemic AL amyloidosis and two patients in whom the diagnosis was suspected, after i.v. administration of about 37 MBq of 131I-SAP. Normal blood pool images were obtained in the latter two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h was 〈60% and 6-h plasma activity was 〉65% of the injected dose (i.d.). Among the other ten patients, amyloid deposits were identified in the spleen in eight cases, liver in five and kidneys in four; other sites that gave positive results included bone, joints and soft tissues, and the myocardium in one case. Up to 95% of the tracer localised into amyloid within 6-h, and the values for WBR became progressively more discriminating during the study period, exceeding the normal reference value (〈25%) in all cases by day 7. The optimal imaging time was found to be between 24 and 48 h. The duration of the study enabled us to measure the tracer elimination half-life which was increased in all cases by up to tenfold. Follow-up studies performed after 2–24 months in four patients who were treated with iododoxorubicin showed regression of amyloid in one patient and a small increase in one case; in the other two patients the imaging and turnover studies were identical to baseline. Despite its unfavourable imaging characteristics, 131I-SAP produced diagnostic scans in every patient in this series and, coupled with the detailed turnover information, is adequate for monitoring disease progress.
    Type of Medium: Electronic Resource
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