Summated Chemotherapy Dose-intensity versus Loco-regional Response in Locally Advanced Breast Cancer: Its Possible Implications

Background: Summated dose-intensity (SDI) of chemotherapy regimen could influence the outcome in malignancies. Aims: To evaluate the implication of SDI and identify key drugs for loco-regional response in locally advanced breast cancer (LABC). Settings and design: This retrospective study was based on audit of records of LABC patients who had received neoadjuvant chemotherapy (NACT). Material and Methods: Actual unit dose-intensity (UDI) of each drug and corresponding SDI of every doxorubicin (n=116 cycles) or non-doxorubicin (n=110 cycles) based NACT received by 42 patients of LABC were summated. Cumulative dose-intensity (CDI) for individual drugs and cumulative SDI (CSDI) for the entire course of NACT were estimated and correlated with quantum of primary tumor, axillary and supraclavicular nodal responses. Statistical analysis used: Two-sided chi-square, t-test, step-wise regression was used. Results: Dose-response curve between CSDI and corresponding responses for both primary and lymph nodes were sigmoid in shape for both doxorubicin or non-doxorubicin based NACT. Curves were best fitted using a cubic fit for all patients (r² = 0.82, 0.84 and 0.93 for primary tumor, axillary and supraclavicular lymph nodes respectively). CSDI emerged as an important prognosticators for both primary (P<0.001) and nodal (P<0.001) responses. Individually, CDI of 5-fluorouracil for primary (P<0.001), CDIs of doxorubicin (P<0.001) and methotrexate (P=0.006) for axillary nodes and CDI of cyclophosphamide (P=0.001) for supraclavicular nodes were significant. Conclusions: Loco-regional responses in LABC are dependent on CSDI of NACT regimen. Drugs for high-dose intensification protocols could be identified and chosen based on the impact of CDI of individual drugs in NACT.

Keywords
Dose-intensity, Dose-response, Locally advanced breast cancer, Neoadjuvant chemotherapy