HIGH-DOSE MULTIMODALITY THERAPY WITH AUTOLOGOUS STEM-CELL SUPPORT FORSTAGE IIIB BREAST-CARCINOMA

Purpose: Women with locally unresectable and inflammatory breast carci noma (IBC) have an approximately 30% 5-year disease-free survival (DFS ) rate with conventional multimodality therapy. A short but dose-inten sive multimodality phase II trial was designed in an attempt to improv e outcome in stage IIIB disease. Mastectomy was performed after high-d ose therapy to evaluate pathologic response to treatment. Methods: Wom en with newly diagnosed disease received four 2-week cycles of doxorub icin 90 mg/m(2) with granulocyte colony-stimulating factor (G-CSF), fo llowed by cyclophosphamide 6,000 mg/m(2), thiotepa 500 mg/m(2), and ca rboplatin 800 mg/m(2) (CTCb) with marrow and peripheral-blood progenit or cell (PBPC) support. Local therapy consisted of mastectomy and radi otherapy. Tamoxifen (5 years) was begun if the patient was estrogen re ceptor-positive (ER+). Results: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mast ectomy before any systemic therapy (seven with pathologic IBC, three w ith residual tumor after mastectomy). Eighty percent received full-dos e doxorubicin with 60% on schedule. Clinical response rates to inducti on were 15% complete response (CR), 5% very good partial response (VGP R), 59% partial response (PR), and 21% minor response (MR)/stable dise ase (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CT Cb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30- month DFS is estimated at 100%, 70%, and 38%, respectively, Those with zero, one to three, or greater than or equal to four positive nodes a t axillary dissection had a median DFS of 31, 18, and 13 months, respe ctively. Conclusion: This short but dose-intensive multimodality appro ach for stage IIIB breast carcinoma is feasible with encouraging resul ts to date. (C) 1998 by American Society of Clinical Oncology.