Dose-dense chemotherapy in breast cancer and lymphoma

Abstract

Adjuvant combination chemotherapy reduces the risk of relapse and death for patients with invasive breast cancer and adds to the benefits obtained with hormonal treatment. Generally, anthracycline-containing regimens are superior to non-anthracycline regimens, treatments longer than 6 months are not advantageous and high-dose chemotherapy regimens, which require autologous hematopoietic stem cell support, have not proved consistently superior. The development and evaluation of the taxanes was highly anticipated as they have shown high levels of efficacy while appearing to be non-cross-resistant with partially non-overlapping toxicities. A role for taxanes in the adjuvant or neoadjuvant setting is now widely acknowledged, although they are not currently approved for treatment of early breast cancer in Europe. In patients with aggressive lymphoma who receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, 40% to 70% of patients attain a complete remission, depending on risk factors such as age and extranodal involvement. Second- and third-generation regimens like m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide), Pro-MACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) have largely failed to improve treatment outcome. The use of monoclonal anti-CD20 antibodies or dose escalation have shown promising results in improving relapse-free and survival rates. In patients with breast cancer, the key Cancer and Leukemia Group B 9741 trial showed that dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy with granulocyte colony-stimulating factor (G-CSF), repeated every 2 weeks, is superior to the same regimen administered at standard 3-weekly intervals. In lymphoma, dose-dense CHOP chemotherapy has shown superiority over standard CHOP regimens, particularly in elderly patients with aggressive non-Hodgkin’s lymphoma. G-CSF factor is essential to enable the administration of dose-dense chemotherapy and any reduction in its use leads to significant increases in infectious complications. Current evidence suggests that dose-dense chemotherapy, enabled by G-CSF, is an important breakthrough in the evolution of chemotherapy for breast cancer and lymphoma.