Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase I/II trials.

PURPOSE: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications.

METHODS AND MATERIALS: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel +/- vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT.

RESULTS

Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively.

CONCLUSIONS

Concurrent WO/WO radiation therapy and paclitaxel +/- vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted.