Previous studies of flavopiridol alone and in combination with chemotherapy, have an MTD of 70 mg/m2 administered best CONFIRMS, as a 1-hour infusion. With a profile Similar DLT consisting of neutropenia, diarrhea and fatigue at this dose appears PK w during cycle 1 to be compatible with other chemotherapy combinations. However, unlike previous studies combining flavopiridol PS-341 with chemotherapy, the wild-type p53 status was not obtained Hter sensitivity correlated. In fact, patients were, the big e tumor regressions had mutated p53. This may indicate different mechanisms to respond to DNA-Sch Be used between the irinotecan and oxaliplatin, irinotecan, so there only p53 dependent dependent. The antitumor activity T was in a variety of tumor types observed in this phase I study, independently Ngig thereof.
Before treatment with platinum Seven of the 42 evaluable patients achieved a CR or PR experiencedeither including 4 patients U had treatment with platinum again. Although the results have been documented with FOLFOX F in our study, in agreement with the data reported EFC4584 GERCOR V308 and studies, the overall response rate of 10% and 15% with FOLFOX alone Dexamethasone second line of cancer c lon advanced, promising activity was t found in the subgroup of patients with platinum refractory GCT treated on this study. Ten patients with platinum-refractory GCT Ren were enrolled on the trial F FOLFOX, prim 5 of them Ren mediastinal tumor or sp Th relapse, two properties that were predicted to save a lack of response to treatment. Among the 9 patients evaluable for radiographic response by RECIST criteria, had 3 PR, 3 had SD and 1 patient had progression in the brain, in spite of an 68% reduction in tumor markers AFP.
The other 2 patients showed progression of GCT on the study after only one treatment. Another patient who had progressed on oxaliplatin 130 mg/m2 had., A 40% decrease in AFP after 1 cycle of FOLFOX F, but was ver Ffentlichten study because of hypersensitivity reactions associated with oxaliplatin For patients with relapsed or refractory Rer GCT optimal treatment regimen has not been established. Up to 40% of patients who are most suitable to be identified after treatment with high-dose therapy in the second row, and some subgroups of patients, as with seminomat Sen GCT GCT refractory prime Ren mediastinal go Become hardened, were of this benefit approach.
Oxaliplatin as a single agent in patients with refractory Rer examined GCT cisplatin with two different doses. One group of patients was treated with 60 mg/m2 weekly on days 1, 8 and 15 every 28 days with an average response time of 6%. A second cohort was treated with 130 mg/m2 every 2 weeks with an objective response rate of 19%. Overall, the combination of FOLFOX and flavopiridol with the activity A variety of solid tumors observed t be tolerated. Ver, taking into account the response rate Ffentlicht oxaliplatin alone, the extent the pretreatment and the high risk nature of refractory GCT treated in this study, the response of the Bev POPULATION GCT is particularly encouraging.