Dose-intense salvage therapy after neoadjuvant chemotherapy: feasibility and preliminary results

Breast cancer patients who, following treatment with primary chemotherapy (FAC 50) present an axillary node involvement of more than 4 nodes together with clinically palpable residual disease (minor response to chemotherapy) and the presence of tumour cell emboli in lymphatics have a very poor outcome. DFS rates of 50 patients treated between 1990 and 1994 were 31% at 5 years. Our aim was therefore to evaluate an entirely different therapeutic regime in these very high risk patients. 32 patients selected for these criteria entered a pilot study consisting in treatment with 3 four weekly cycles of vinorelbine, ifosfamide, cisplatinum followed by a high dose chemotherapy (HDCT) course and rescue by peripheral hematopoietic stem cells which had been collected by cytapheresis after the second course of chemotherapy. HDCT consisted of thiotepa, L-Pam, CBDCA (800 mg/m(2) d1), ifosfamide and mesna. Following primary chemotherapy, 14 patients had breast conservation and 18 had a modified mastectomy. Median number of involved lymph nodes was 11 (range 4-26). 29 patients received the complete HDCT course. Median age was 40 (range 24-59). Engraftment was prompt with a median of 10 days to leucocyte recovery to 1,000/microl and 9 days to platelet recovery. One patient developed reversible renal failure, and subsequently died of Gram-septicemia. To date, with a median follow up of 20 months (range 14-36), 6 patients have relapsed and 2 patients have died. It is too early to make any firm conclusions, but we feel that this alternative regime is feasible and may prove superior to the classical optimal dose anthracycline-containing regimes in patients who have a tendency to rapidly develop resistance to anthracyclines.