A Phase III Study of High-Dose Intensification Without Hematopoietic Progenitor Cells Support for Patients With High-Risk Primary Breast Carcinoma

Abstract

Patients with more than nine ipsilateral lymph node involvement or inflammatory breast cancer have a 5-year survival rate of approximately 50%. We studied the efficacy of high-dose intensification, comparing it with the standard dose chemotherapy for patients with high-risk primary breast cancer. Patients with inflammatory breast cancer or more than nine ipsilateral lymph node involvement without evidence of distant metastasis were randomized to receive either standard dose 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for nine courses (control) or six courses of FAC followed by two courses of cyclophosphamide (5.25 g/m2), etoposide (1,500 mg/m2), and cisplatin (165 mg/m2) (HDCVP). The study was terminated in 1998 because of slow accrual of patients. Forty-six patients were entered in the study. At 4 years, the overall survival was 72.8% (SE 11.9%) and 61.7% (SE 12.4%), and disease-free survival were 45.5% (SE 12.3%) and 33.7% (SE 11.9%) for the control and HDCVP groups, respectively (p = 0.757 and 0.720). With the small number of patients in our study, a small overall survival benefit of high-dose intensification compared with the standard therapy cannot be excluded. However, any substantial benefit is unlikely.

High‐dose mitoxantrone and cyclophosphamide without stem cell support in patients with high‐risk and advanced breast carcinoma

“…Neidhart et al45 reported a Phase II trial in which 51 patients with refractory malignancies were treated with high doses of CTX, etoposide, and cisplatin with CSF support, and they described 6 nondisease‐related deaths within 30 days after completing treatment. Finally, a small randomized trial compared nine cycles of conventional fluorouracil, doxorubicin, and CTX with six courses of the same combination followed by two cycles of HDC, including CTX, etoposide, and cisplatin, without stem cell support as adjuvant treatment for patients with HRBC 46. Even though no significant survival differences were observed, the number of patients was very low—the trial prematurely was closed due to slow accrual—and only 16 of 23 patients in the HDC arm actually received such treatment.…”