Several clinical trials (including EST-2190) have tested high-dose chemotherapy with bone marrow transplant (BMT) or stem cell support in women with more than ten positive lymph nodes and in women with four to nine positive lymph nodes.[181,182,183,184,185,186,187,188] A prospective randomized trial of 403 patients testing the use of two tandem high-dose chemotherapy courses demonstrated a statistically significant (P = .02) difference in 5-year survival (75% vs. 70%) with a 49-month median follow-up.[Level of evidence: 1iiA] The remaining trials comparing conventional chemotherapy to high-dose chemotherapy with BMT or stem cell support in high-risk patients in the adjuvant setting indicated no OS or EFS benefit from the high-dose chemotherapy with BMT or stem cell support.[181,182,183,184,185,186,188,189,190][Level of evidence: 1iiA] The information to date does not support the use of high-dose chemotherapy outside the context of a randomized clinical trial.
Also, a systematic review of nine randomized controlled trials comparing the effectiveness of high-dose chemotherapy and autograft with conventional chemotherapy for women with early poor prognosis breast cancer was performed. In total 1,758 women were randomly assigned to receive high-dose chemotherapy with autograft, and 1,767 women were randomly assigned to receive conventional chemotherapy. There were 48 noncancer-related deaths on the high dose arm and four on the conventional dose arm (RR = 7.74; 95% CI, 3.43-17.50). There was no statistically significant difference in OS between women who received high-dose chemotherapy with autograft and women who received conventional chemotherapy, either at 3 years (RR = 1.02; 95% CI, 0.98-1.06), or at 5 years (RR = 0.98, 95% CI, 0.93-1.05). There was a statistically significant benefit in EFS at 3 years for the group who received high dose chemotherapy (RR = 1.11; 95% CI, 1.05-1.18). However, this significance was lost at 5 years (RR = 1.00; 95% CI, 0.92-1.08).
Other chemotherapy regimens
The NSABP-B-19 trial compared CMF to sequential methotrexate followed by 5-FU in 1,095 women with node-negative, ER-negative tumors. After 13 years of follow-up, an overall benefit was seen for CMF relative to methotrexate plus 5-FU (MF) (RFS: HR = 0.59; 95% CI, 0.45-0.77, P < .001; OS: HR = 0.71; 95% CI, 0.55-0.92; P = .01). All age and menopausal groups demonstrated an RFS benefit, and most demonstrated an OS benefit.[Level of evidence: 1iiA] Serious toxicity (=grade 3), especially febrile neutropenia, was more frequent among CMF-treated patients. With no outcome advantage in older women and more toxic effects from the CMF regimen, the results of this study suggested that methotrexate followed by 5-FU was a reasonable substitute for CMF for older women.