Martin_2011_J.Clin.Oncol_29_1008

1008 Background: X, 1,250 mg/m2 bid, d1-14 q21d (Xint) is an approved regimen in MBC, but is associated with dose-limiting toxicities. Thus, we designed this randomized phase II study to investigate whether continuous dosing of X (Xcont) could reduce the severity of side effects while maintaining the total cumulative dose and efficacy.
METHODS: Pts with evaluable MBC, normal organ function, ECOG PS <=2 and <=2 prior regimens in the metastatic setting were eligible and randomized to X 800 mg/m2 bid, d1-21 q21d Xcont or Xint q3w. Study endpoints: safety (CTCAE v2.0), TTP, ORR, PFS, DOR, OS.
RESULTS: 196 pts were randomized to Xcont (n=99) or Xint (n=97) until progression or unacceptable toxicity. Baseline characteristics were balanced between Xcont and Xint with a median age of 60 yrs (29-88); 21% and 22% were hormone receptor negative; 20% and 16% had prior neoadjuvant chemo; adjuvant therapy had been administered in 76% and 77%, respectively; 56% had visceral involvement in each arm. X was administered as first-line in 45% and 36% of pts, respectively. Prior anthracyclines plus taxanes had been administered to 80% and 89%, in Xcont and Xint, respectively. This preliminary analysis is based on the ITT population: Best RECIST ORR was 29% and 25%, with Xint and Xcont, respectively. Median PFS: 244 vs 187 days (HR 0.69, 95% CI 0.46-1.05), respectively. The relationship between X-induced HFS and 13 polymorphisms in the genes involved in the drug metabolism and target gene (the carboxylesterase 2, cytidine deaminase, thymidine phosphorylase, dihydropyrimidine dehydrogenase gene and thymidylate synthase) will be reported. Grade 3/4 toxicities that differ between groups are reported in the table.
CONCLUSIONS: The ongoing evaluation suggests that Xcont has a lower incidence of related AEs. It is too early to draw any conclusion about efficacy, mature data will be presented at the meeting. [Table: see text].