Dose-dense adjuvant chemotherapy for primary breast cancer

Abstract

Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton-Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice.

Figure 1

More frequent dosing can prevent cancer cell regrowth.

Figure 2

Cancer and Leukemia Group B (CALGB) 97-41 node-positivetrial: 2 × 2 factorial design. G-CSF, granulocyte colony-stimulating factor.

Figure 3

Disease-free survival by density. Adapted from Citron and coworkers [19].

Figure 4

Overall survival by density. Adapted from Citron and coworkers [19].

Figure 5

Phase III, prospective, randomized, multicenter Arbeitsgemeinschaft für Gynaekologische Onkologie group trial. Adapted from Möbus and coworkers [21].

Figure 6

Phase III adjuvant trial comparing standard versus accelerated 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) regimen in early breast cancer patients. Results from the Gruppo Oncologico del Nord-Ovest group MIG1 study. G-CSF, granulocyte colony-stimulating factor. Adapted from Venturini and coworkers [22].

Figure 7

Memorial Sloan-Kettering Cancer Center Pilot trial of epirubicin and cyclophosphamide followed by paclitaxel at 10–11 day intervals. G-CSF, granulocyte colony-stimulating factor.