Y PARP cleavage was, they PDE Inhibitor in clinical trials were treated mainly in cells with doxorubicin, followed sequentially observed by the combination of flavopiridol. In vivo mouse models of human xenografts showed that flavopiridol monotherapy reduced tumor growth compared to untreated controls and was significantly more effective than doxorubicin alone. As we have already noted that the timing of chemotherapy compared with flavopiridol k Can influence the degree of tumor regression in vivo, we treated ourselves to our tumor xenografts with doxorubicin, followed by flavopiridol at 1, 4 and 7 hours and with the reverse combination a distance of 7 hours. In Figure 1B, the only combination, statistically superior to doxorubicin alone was shown doxorubicin followed by 1 hour sp Ter flavopiridol. All other combinations were either equal to or less than doxorubicin alone. There was no significant weight loss with the combined therapy.
Interestingly, when compared with flavopiridol be F1combination D, it seems a trend toward tumor growth is less than the combination, but it did not reach statistical significance. These data are consistent with previous observations that dedifferentiated liposarcoma cell lines with CDK4 verst RKT, very sensitive to flavopiridol and the clinical observation that dedifferentiated liposarcomas are generally resistant to doxorubicin. Given these results, we initiated a phase I dose escalation of flavopiridol in combination with doxorubicin. The main objective of this study was to determine the MTD of flavopiridol in combination with doxorubicin, in patients Glutamate receptor with advanced sarcoma. Secondary Re targets were the clinical pharmacokinetics of flavopiridol in combination with doxorubicin and to study vorl Ufigen to obtain data on the therapeutic efficacy of this system. Characteristics of patients in clinical trials resulting from 10/13/2004 to 14/01/2010, 31 patients with metastases or local recurrence of sarcoma were recorded and treated 30th One patient was not evaluable for DLT determine that the patient does not initiate treatment after registration. Three patients were not evaluable for the determination of the response, because they have not completed two treatment cycles.
The reasons were withdrawal of consent and clinical deterioration. Table 2 summarizes the characteristics of the patients of 31 patients are carried out by the protocol. The average age was 57 years and the median Karnofsky performance status was 90%. There were 20 M Men and 11 women. Sarcomas treated and the number of patients had liposarcoma, leiomyosarcoma, fibrosarcoma, malignant peripheral nerve sheath, undifferentiated pleomorphic sarcoma, osteosarcoma, rhabdomyosarcoma, gastrointestinal stromal tumors and tumor solitaryfibrous. The majority of patients had no new U prior chemotherapy with a total range of 0 2 previous treatments. None of the patients had recovered U doxorubicin Formononetin before and all had to start progressive disease at the time of registration with an indication of treatment systems. Table 3 summarizes the toxicity of t the h Ufigsten h Dermatological toxicity Th grade 2 April for the first cycle of treatment. Combined treatment with flavopiridol and doxorubicin 60 mg/m2 bolus than 1 hour has been documented to be tolerated without DLT.
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