Sequential Doxorubicin/Docetaxel and Simultaneous Regimen Equally Effective for Metastatic Breast Cancer

The results of a multicenter, phase III metastatic breast cancer study indicates that, in women with previously untreated metastatic breast cancer, sequential chemotherapy induction using doxorubicin and docetaxel (Taxotere) is as effective and safe as standard simultaneous induction but does not improve the response to treatment. These results were presented by Response Oncology, Inc., a comprehensive cancer management company based in Memphis, at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).

The study included 98 newly diagnosed patients. One group received the standard doxorubicin/docetaxel combination schedule in which the drugs were given simultaneously every 21 days. The second group was given a dose-dense sequential schedule—a maximal dose of doxorubicin with minimum cycle length prior to delivery of docetaxel, which was administered in the same fashion.

Following induction, stable and responding patients received high-dose consolidation therapy with stem-cell support. The overall response rate at the end of induction was similar for both the simultaneous and sequential induction groups: 66% and 65%, respectively.

The two treatments were equally safe and well tolerated. However, the simultaneous induction schedule produced a higher rate of neutropenia, whereas the sequential schedule resulted in a higher rate of anemia and skin reaction.

Study Design

The trial included women with previously untreated stage IV breast cancer who had received a prior cumulative doxorubicin dose of 300 mg/m² or less. Participants ranged from 18 to 65 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. All patients had measurable disease.

Women who had failed doxorubicin treatment within the last 12 months and/or had undergone prior taxane treatment were excluded. At the time of their diagnosis, 37% of the women had metastatic disease and 54% had undergone prior adjuvant therapy. The disease had spread to the liver in 31%.

The simultaneous induction group received both doxorubicin, 45 mg/m², and docetaxel, 75 mg/m², administered intravenously every 21 days for four treatment cycles. The sequential induction group received 90 mg/m² of doxorubicin intravenously every 14 days for two treatment cycles followed by 100 mg/m² of docetaxel administered intravenously every 21 days for three cycles.

Treatment Response

Response was assessed 3 to 4 weeks after induction. The complete response to simultaneous induction was 28%, compared with 18% in the sequential induction group. The partial response rates were 45% and 51%, respectively.

Among patients in the simultaneous induction group, 16% had stable disease at follow-up, and 11% had disease progression. The rates of stable disease and disease progression in the sequential induction group were 21% and 10%, respectively. There were no significant differences between the two treatment groups in any of the response measures.

The most common side effect was neutropenia, which occurred more often in the simultaneous arm (67% vs 34%) due to the differences in the support medications. Gastrointestinal, neurologic, infectious, and hyperglycemic side effects occurred equally in both groups. Skin reactions occurred more frequently in the sequential arm of the study.

The median delivered dose intensity and cumulative dose were similar in the two treatment arms. However, median dose density was markedly higher for the sequential arm.

Conclusions

It has been suggested that the dose-dense schedule may improve the results of chemotherapy in women with metastatic breast cancer. “Our findings indicate that combination chemotherapy with doxorubicin and docetaxel is effective and well tolerated with both induction schedules,” said Lee S. Schwartzberg, MD, associate scientific officer of Response Oncology, Inc. “Sequential induction does not offer any advantages over conventional induction treatment in these patients.”