Phase I study of preoperative chemoradiation therapy in unresectable locally advanced breast cancer (LABC)

Abstract

11097 Introduction: Therapy of unresectable LABC is challenging due to the need to resect local disease and prevent distant metastases. We conducted a phase I trial to determine the maximum tolerated dose of preoperative vinorelbine (VIN) combined with paclitaxel (P) and radiation (XRT). Methods: Eligible patients (pts) had unresectable LABC, ECOG performance 0–2 and adequate organ function. Prior chemotherapy and metastatic disease were permitted. All pts received weekly bolus P 80 mg/m2 and concurrent XRT at 2.0 Gy daily for 5 days in a week-on/week-off (WO/WO) schedule for 12 weeks. A planned 59 -70 Gy were delivered to the breast, chest wall and supraclavicular regions. In dose level 2, VIN 15 mg/m2 /week was added. Results: Twenty-six pts were enrolled from July 1999-July 2005 with a median age of 51 years (range 24–69); 9 pts had stage IV disease, 17 pts had stage IIIB disease, and 13 pts had received prior chemotherapy. VIN was not tolerated due to grade (G) 4 neutropenia despite GCSF; however single-agent P and concurrent XRT was well-tolerated. Thus, 7 pts in the final cohort received P/XRT without GCSF. This regimen was well-tolerated; toxicities seen included: G3 in-field skin desquamation 4/7; G4 lymphopenia 7/7, G3 infection 1/7; G3 wound dehiscence 1/7. After therapy, 20/26 pts underwent mastectomy: 6 pts had a pathologic complete response (no invasive disease), 12 had a pathologic partial response (scattered microscopic disease), and 2 pts had no response. Overall pathologic response rate was 90% for pts undergoing mastectomy; only 3 of the 20 resectable pts are alive without relapse a mean of 19.5 months after mastectomy. Conclusions: Neoadjuvant P 80 mg/m2 with full dose XRT in a WO/WO schedule is tolerable and effective allowing 20/26 unresectable pts to undergo successful mastectomy. Pts do not require routine GCSF support. Although most pts eventually relapse distantly, this regimen does render some pts not responding to initial doxorubicin-based therapy resectable. [Table: see text] No significant financial relationships to disclose.