Locally Advanced Breast Cancer patients require neoadjuvant chemotherapy (NACT), surgery and radiation therapy to optimize the chance of a cure. Pathological responses to NACT, are strongly associated with long-term outcome. Cisplatin has shown antitumor activity in breast cancer, shows synergy with paclitaxel and antitumor activity in anthracycline-resistant breast tumors. As NACT, Paclitaxel-Cisplatin (PC) achieves high pathological responses. On the other hand, dose dense chemotherapy has improved free and overall survival in early breast cancer. This phase II trial was set to evaluate the pathological complete response (pathCR) of this regimen based on 4 cycles of adriamycin/cyclophosphamide (AC) followed by weekly (dose dense) PC. Secondary endpoints were to evaluate the safety profile and recurrence-free survival.
Materials and methods
Patients with histological confirmation of breast cancer in stage IIB-IIIC and aged 18–75 years. Patients also had good performance status [ECOG] score ≤2, adequate hematological, cardiovascular, renal, and hepatic functions. Patients were excluded if they were pregnant or breast feeding or if they had other malignant tumors. Patients received 4 cycles of AC at 60/600 mg/m2 every 21 days followed by weekly PC at 80/30 mg/m2 respectively, at the end of chemotherapy patients underwent surgery.
A total of 33 patients were included and were evaluable for toxicity and response; the analysis was done in the intention-to-treat. One patient showed paclitaxel hypersensitivity and was removed from the study. Three patients remained inoperable after chemotherapy, hence, received preoperative radiation. Median age was 48 years-old (26–73), 66.7% of cases were in stage IIIA and IIIB, tumor median size was 6 cm (2.5–16), node median size was 3 cm (2–16), all patients had clinical positive nodes. ER or PgR were positive in 60.6%, HER2 was positive in 36.4% (determined by IHC or FISH). The pathCR rate was 30%, the complete nodal response was 52%. At 18 months of follow-up 2 patients had distant relapse for a 91% of recurrence free-survival. The regimen was well tolerated with grade III-IV toxicity observed in 6% of cases.
The addition of cisplatin to paclitaxel is well tolerated with no significant increase in toxicity. Interestingly, the 30% of pathCR observed seems superior to other regimens without cisplatin.