CNS effect, mainlyto a significant degree. In CNS disorders, which may confess Rte BBB permeability t VER Be changed to the passage of lapatinib. In a pr Clinical model, lapatinib has been shown to inhibit the formation of brain metastases in breast OSU-03012 AR-12 cancer xenograft .32 In this mouse model, lapatinib inhibits phosphorylation of EGFR, HER2 and related proteins Downstream Rts. Interestingly, lapatinib inhibits the formation of big s metastases but not completely Prevent ndig, metastasis, indicating a resistance in some breast cancer cells. Lapatinib activity t of the central nervous system disease in patients heavily pretreated encourages further research into the definition of its R In the treatment of CNS metastases.
In the Phase III study GSK1363089 of lapatinib and capecitabine, the number of patients had metastases to the central nervous system in the combination of lapatinib monotherapy group, vs, but that was not statistically significant.11 An analysis of the Phase II lapatinib in patients with MBC new or progressive brain metastases after treatment with trastuzumab showed a patient with RA and 7 patients with stable CNS and non-CNS disease at 16 weeks.33 within this study, an exploratory analysis evaluating pleased with volumetric, RECIST for that t L emissions of central nervous system longer TTP in patients � proposed 0% volumetric reduction. Although these studies have not reached their prime Ren efficacy endpoint goal for the response rate to RECIST criteria defined prospectively based, are volumetric certainly encouraging.
Preferences INDICATIVE data from a sp Teren study with a volumetric reduction of CNS-L Emissions as their prime Ren endpoint showed � Volumetric reduction of 0% for 17 patients in whom the median time to progression at 16 weeks.34 volume Final results are expected. In addition, provided an extension of the test patients with CNS and / or non-CNS progression on lapatinib alone, the M Opportunity, combining lapatinib and get capecitabine.35 Preferences INDICATIVE results showed � 0% reduction FINISH 8 patients on what the activity t of lapatinib capecitabine on resistance to lapatinib monotherapy. Lapatinib Lapatinib reps Possibility is generally well tolerated Possible treatment.
In phase I and II trials with lapatinib monotherapy with a temporary Class 1 February was associated rash, diarrhea, nausea / vomiting, stomatitis reported fatigue and loss of appetite, that h Ufigsten undesirable degree 7,13,15,16 events.4 3 toxicity Th were rare, but were diarrhea, rash, Leberfunktionsst ments, and gastrointestinal toxicity events.5 7 No t lapatinib was attributable to grade 4 reported.5 7.13 was drug-related cardiac toxicity 16 No t observed. This seems in contrast to the reversible cardiomyopathy with trastuzumab therapy should be seen, although no direct comparative data are available. There was no interstitial pneumonia associated with drugs. Diarrhea Diarrhea associated lapatinib correlated with the dose, but not with serum concentration.7 This suggests that the diarrhea is a local effect on the intestinal epithelium. The question of dosage instructions relevant to k Can, because it dose-diarrhea Ngig is. Lower doses because of the administration with food or twice a day schedule may be associated with less diarrhea. A combined analysis of nine clinical stage I-III was carried out to the diarrhea associated with lapatinib alone or in combination with capecitabine and lapatinib ranged investigate taxanes.36 doses of 1000 t