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High-Dose Chemotherapy Plus Stem-Cell Transplantation May Reduce Risk of Relapse But Does Not Improve Survival for Women with High-Risk Breast Cancer

High-dose chemotherapy with stem-cell transplantation confers some reduced risk of relapse in certain women with high-risk breast cancer but does not improve overall survival when compared with high-risk breast cancer patients who receive conventional-dose chemotherapy, according to the findings of 2 studies.

The first study, Sjoerd Rodenhuis, MD, of the Netherlands Cancer Institute, in Amsterdam, and colleagues, analysed the efficacy of conventional-dose compared with high-dose chemotherapy combined with autologous peripheral-blood hematopoietic progenitor-cell transplantation in a cohort of 885 women (younger than 56 years of age) with 4 or more tumour-positive axillary lymph nodes.

The 443 women in the conventional-dose arm received 5 intravenous courses of fluorouracil (500 mg/m² of body surface), epirubicin (90 mg/m² of body surface), and cyclophosphamide (500 mg/m² of body surface) every 3 weeks. The 442 women assigned to the high-dose group received 4 courses of the same, followed by a final course cyclophosphamide (6 gm/m² of body surface), thiotepa (480 mg/m² of body surface), and carboplatin (1600 mg/m² of body surface) infused daily over a 4-day period. The high-dose group then received peripheral-blood progenitor cells 48 hours after their last chemotherapy dose followed by daily treatment with filgrastim.

After a median follow-up of 57 months, the researchers report 5-year relapse-free survival rates of 59% in the conventional-dose and 65% in the high-dose group. In patients with 10 or more positive nodes, relapse-free survival was 51% in the conventional-dose and 61% in the high-dose group.

However, Dr. Rodenhuis' group found no significant difference in overall survival between the treatment groups at the time of last follow-up. They conclude that this high-dose chemotherapy regimen improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes.

In another study Martin S. Tallman, MD, Northwestern University Feinberg School of Medicine, in Chicago, Illinois, United States, and colleagues compared high-dose chemotherapy and autologous hematopoietic stem-cell transplantation therapy with conventional chemotherapy in women with primary breast cancer involving at least 10 ipsilateral axillary lymph nodes.

All 511 patients (median age of 44 years) received 6 cycles of oral cyclophosphamide (100 mg/m² of body surface on days 1 through 14), and, on days 1 and 8, intravenous doxorubicin (30 mg/m² of body surface), and fluorouracil (500 mg/m² of body surface). The high-dose group (N=254) also received continuous intravenous infusion of cyclophosphamide (6 g/m² of body surface) and thiotepa (800 mg/m² of body surface) on days 6, 5, 4, and 3, prior to the infusion of autologous bone marrow, peripheral-blood stem cells, or both.

With a median follow-up of 6.1 years the 6-year disease-free survival rate was 47% in the conventional and 49% in the high-dose group. The 6-year overall survival rate was 62% in the conventional versus 58% in the high-dose group.

When Dr. Tallman's group analysed of a subgroup of 417 patients who strictly fulfilled study eligibility requirements they found that 45% of the conventional group compared with 55% of the high-dose group were recurrence free at 6 years. This suggests, the researchers report, the addition of stem-cell transplantation may enhance the antitumour effect more than does 6 cycles of conventional chemotherapy.

However, high-dose chemotherapy plus autologous stem-cell transplantation offered no significant benefit over conventional chemotherapy in disease-free survival or overall survival among women with stage II or III breast cancer and at least 10 involved ipsilateral axillary lymph nodes. Dr. Tallman's team concludes that conventional-dose chemotherapy remains the standard of care for such patients.


Related Link:Conventional Adjuvant Chemotherapy with or without High-Dose Chemotherapy and Autologous Stem-Cell Transplantation in High-Risk Breast Cancer (N Engl J Med 2003;349:1:17-26).
N Engl J Med 2003;349:1:7-16. "High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for High-Risk Breast Cancer"

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