Kinetic analysis of breast tumor decay and growth following ixabepilone plus capecitabine (IXA + CAP) versus capecitabine alone (CAP) to discern whether the superiority of the combination is a result of slower growth, enhanced tumor cell kill, or both.

Abstract

1096 Background: Utilizing a new method that analyzes tumor measurements obtained while a patient receives chemotherapy, we have previously shown for prostate and renal tumors that the growth rate constant of a tumor correlates with survival (Stein et al, Oncologist, 13:1046 and 1055; 2008). We have now applied this same approach to data collected in a clinical trial of IXA + CAP versus CAP alone in patients with metastatic breast cancer (MBC). Methods: Using CT tumor measurements obtained while patients were treated we determined the rate of tumor decay (d) and growth (g) reliably even before the nadir is reached. Results: (i) In patients treated with CAP, overall survival (OS) was strongly correlated (R > 0.59, p < 0.001) with the rate of tumor growth (log g) but less strongly (R > 0.21, p > 0.028) with the rate of decay (log d). The median growth rate constant for these tumors was 0.00288 days-1. For IXA + CAP, correlations of OS with both log g (R > 0.57, p < 0.001) and log d (R > 0.27, p > 0.0003) were similar to those for CAP. The median g value for IXA + CAP at 0.00191 days-1 was significantly lower than for CAP (p < 0.001), while median d values were similar (0.00840 days-1 for CAP; 0.00863 days-1 for CAP + IXA, p > 0.400 NS). (ii) For neither arm did g or d correlate with initial tumor burden. (iii) The median OS for the patients in this analysis treated with IXA + CAP (475 d) was significantly longer (p > 0.02) than that for the group treated with CAP (392 d) - in strict proportion to the reduction in the tumor growth rate constant. (iv) These median OS values were, however, shorter than those predicted from the on-study g and d parameters, suggesting continuation of drug treatment might have resulted in an increase in OS. Conclusions: We present a quantitative kinetic analysis of the response of breast tumors to chemotherapy as a robust and rapid method to assess results of clinical trials. Reduction of the on- study tumor growth rate with the addition of IXA was responsible for the enhanced OS seen with the combination. Continuation of treatment with IXA might conceivably have extended patient survival even further. No significant financial relationships to disclose.