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  • platinum analog  (1)
  • stem cells  (1)
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  • 1
    ISSN: 1569-8041
    Keywords: breast cancer ; G-CSF ; mobilization ; stem cells ; transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We compared hematopoietic progenitor cell (HPC) collection and neoplastic cell contamination in breast cancer patients given cyclophosphamide (CTX) plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization. Patients and methods: In 57 stage II–III breast cancer patients, CD34+ cells, colony-forming units-granulocyte macrophage (CFU-GM), early HPC and breast cancer cells were counted in HPC collections obtained after CTX plus G-CSF (n = 27) or G-CSF-alone mobilization (n = 30). Results: The CD34+ cell collection was about two-fold greater after CTX plus G-CSF mobilization (11.0 ± 7.9 vs. 5.8 ± 3.5 × 106/kg, P 〈 0.001). Similarly, the total number of CFU-GM, CD34+CD38− cells and of week-5 cobblestone area forming cells (CAFC) collected was significantly higher in patients mobilized with CTX plus G-CSF. Breast cancer cells were found in the apheresis products of 22% of patients mobilized with CTX plus G-CSF and in 10% of patients mobilized with G-CSF alone (P = 0.36). Of seven patients who failed G-CSF-alone mobilization and eventually underwent chemotherapy plus G-CSF mobilization, none had cytokeratin-positive cells after G-CSF mobilization, whereas four out of seven had cytokeratin-positive cells after chemotherapy plus G-CSF (P = 0.07 by χ2 test). Conclusion: The CTX plus G-CSF mobilization protocol was associated with a significantly higher HPC collection. However, this benefit was not accompanied by a reduction in the incidence of tumor-contaminated HPC graft.
    Type of Medium: Electronic Resource
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  • 2
    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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