Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

Background: Uncontrolled studies have reported encouraging outcomes for pat ients with high-risk primary breast cancer treated with high-dose chemother apy and autologous hematopoietic stem cell support. We conducted a prospect ive randomized trial to compare standard-dose chemotherapy with the same th erapy followed by high-dose chemotherapy. Patients and Methods: Patients wi th 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of prima ry (neoadjuvant) chemotherapy were eligible. All patients were to-receive e ight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphami de (FAC), Patients were stratified by stage and randomly assigned to receiv e two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with a utologous hematopoietic stem cell support or no additional chemotherapy, Ta moxifen was planned for postmenopausal patients with estrogen receptor-posi tive tumors and chest wall radiotherapy was planned for all. All P values a re from two-sided tests. Results: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine pat ients were randomly assigned to FAC and 39 to FAC followed by high-dose che motherapy, After a median follow-up of 6.5 years, there have been 41 relaps es, In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P = .35), and 3-year survival rates were 77% and 58%, respectively (P = . 23), Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associate d with high-dose chemotherapy, Conclusions: No relapse-free or overall surv ival advantage was associated with the use of high-dose chemotherapy, and m orbidity was increased with its use. Thus, high-dose chemotherapy is not in dicated outside a clinical trial.