Neoadjuvant chemotherapy has practical and theoretical advantages over
adjuvant chemotherapy strategy in
breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic
chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly
paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly
doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral
cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly
trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed
hormone receptor positivity in
tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more
tumors lacking
hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed
pneumonitis, and in the TAME cohort we observed more hematological toxicity and
hand-foot syndrome. The neoadjuvant metronomic
chemotherapy regimen evaluated in this trial was highly effective in achieving a
tumor response, especially in the HER2+ cohort.
Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic
chemotherapy and
trastuzumab treatment.