Abstract:
Purpose/Objective: The management of FABC remains a major challenge because of the competing risk of local and distant disease. A phase I/II trial of concomitant chemotherapy and radiation (CRT) was initiated to attempt to address both local and distant disease. Materials/Methods: Between 1995 and 2001, 29 patients (pts) were enrolled on two consecutive phase I/II trials of CRT consisting of paclitaxel +/- vinorelbine with filgrastim (G-CSF) support. Eligible patients were unresectable locally advanced or inflammatory breast cancers (T4NxM0-1), including recurrent or metastatic patients. 14 pts had stage IIIB disease, 3 were recurrent and 12 were stage IV. Pts were treated on a week on, week off (WOWO) schedule consisting of CRT on days 1-5 and no treatment on days 6-14 for 6-7 cycles. Pts were given 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics. 15 patients (51.7%) underwent mastectomy after CRT. 21 patients in this protocol were treated with vinorelbine 15-20 mg/m2 on day 1 with paclitaxel 20-80mg/m2 (IV bolus or continuous infusion) concurrent with RT (PV+RT). 8 patients received IV bolus paclitaxel 80 mg/m2 with RT (P+RT). Toxicity was graded using RTOG acute and late toxicity scales. Separate analyses for actuarial rates of local recurrence (LR), disease free survival (DFS) and overall survival (OS) were undertaken for stage IIIB and recurrent/metastatic patients. Results: 9 pts developed grade 4 acute hematologic toxicity with 4 pts developed neutropenic fever. 43% of pts receiving PV+RT developed grade 4 neutropenia vs. 0% treated with P+RT, p=0.03. There was no grade 5 toxicity. There were 9 cases of acute grade 2 skin toxicity and 2 cases of grade ≧3 acute skin toxicity. 5 pts required a treatment delay during treatment. Late complications included 3 cases of post-surgical complications (wound healing delay, hematoma, infection), 4 with decreased arm motion and 10 pts with lymphedema. TRAM/implant loss occurred in 2 of 6 pts undergoing reconstruction. 7 pts developed grade 2-3 late skin toxicity. 2 pts developed grade 2 pneumonitis. There was no cardiac toxicity, rib fracture or brachial plexopathy. Among pts with stage IIIB breast cancer, 12 of 14 (86%) pts proceeded to mastectomy with negative margins. 6 of these pts had a pathologic complete response (pCR). 1 patient died from a motor vehicle accident (MVA) during treatment and 1 developed metastatic disease prior to mastectomy but had a biopsy proven pCR. 6 of 7 (86%) receiving PV+RT achieved a pCR compared to 1 of 7 (14%) pts receiving P+RT, p=0.008. Median follow up for surviving pts is 35.3 months (10-65 months). Patterns of failure are as follows: 2 of 14 pts failed locally, 4 failed distantly only, 7 are NED and 1 had a fatal MVA. All 7 pts with a pCR are locally controlled vs. 4 of 6 with less than a pCR (p=0.10). Actuarial LC at 2 and 4 years was 81%, DFS at 2 and 4 years was 44% and OS at 2 and 4 years was 60 and 50% respectively. For pts with recurrent or metastatic disease, LC was achieved in 11 of 15 (73%) pts. LC was obtained in all 9 pts with a clinical complete response or who proceeded to mastectomy. All pts had evidence of distant progression. Median time to progression was 4.5 months with a median OS of 9 months. 1 year and 2 year OS was 40% and 22% respectively. Conclusions: These pilot data demonstrate that concurrent paclitaxel based chemotherapy with radiation therapy on a WOWO schedule is feasible in locally advanced breast cancer. High rates of pCR can be achieved with this approach. Long-term tumor control and survival are encouraging in unresectable stage IIIB pts. Distant failures predominated in this patient population and investigation of more active systemic therapy is warranted. Toxicity with this approach was acceptable.
Questions about this event email: jkao@radonc.uchicago.edu