Aggressive 16-Week Multidrug Regimen Improves Breast Cancer Survival

LOS ANGELES--An aggressive 16-week, multidrug chemotherapy regimenafforded a survival advantage over six cycles of CAF (cyclophosphamide,Adriamycin, and fluorouracil) in 646 women with receptor-negative,node-positive breast cancer, preliminary results of an Intergroupstudy have shown.

In this early analysis, women treated with the 16-week regimenhad a better 3-year overall survival rate than those who receivedCAF (84% vs 76%), John H. Fetting, MD, associate professor ofoncology, The Johns Hopkins University School of Medicine, reportedat the American Society of Clinical Oncology (ASCO) meeting.

Disease-free survival at 3 years also favored the 16-week treatmentprogram (71% vs 64%, respectively). Although there was a trendtoward fewer recurrences in the group treated with the 16-weekregimen, this difference did not reach statistical significance,Dr. Fetting said.

Just over half of the study participants were premenopausal, slightlymore than half had between 1 and 3 positive nodes, and the majority(more than 85%) had T1 or T2 tumors.

Patients assigned to the CAF arm received six 28-day cycles ofCAF, whereas those randomized to the 16-week regimen receivedeight 2-week cycles, in which cyclophosphamide, doxorubicin, vincristine,methotrexate, fluorouracil, and leucovorin were given on odd-numberedweeks and a 2-day continuous infusion of fluorouracil was givenon even-numbered weeks.

The 16-week regimen developed at Johns Hopkins is based on threeprinciples: (1) rapid exposure of the tumor to multiple activeagents, (2) dose intensity, and (3) optimal administration ofantimetabolites.

Dose intensity, in particular, may have been responsible for thesuperior survival attained with the 16-week regimen, Dr. Fettingsaid. The dose of doxorubicin in the 16-week regimen was 30% higherthan that in the CAF regimen (17 vs 13 mg/m²/wk) and thefluorouracil dose was approximately 2.5 times higher (534 vs 219mg/m² /wk), he noted. The addition of methotrexate and vincristineto the 16-week regimen may also have contributed to the favorableresults.

Despite its greater dose intensity, the 16-week regimen was notassociated with a higher rate of serious side effects, includingneutropenia, Dr. Fetting said. However, grade 3 or higher mucositisoccurred in 20% of patients on the 16-week arm, compared with9% of those on the CAF arm. Moreover, the 16-week regimen decreasedpatients' quality of life to a greater extent than did the standardCAF regimen.

The superior survival in the 16-week-regimen group compared withthe CAF group was due to fewer deaths from breast cancer (63 vs45), as well as fewer treatment-related deaths (3 vs 0), Dr. Fettingsaid. All the treatment-related deaths in the CAF recipients weredue to infections or other events that occurred during periodsof neutropenia.