my personal edition > breast cancer > news


  E-Mail this DGReview to a colleague

DGReview

Sequential, Alternating, or Combination Doxorubicin/Docetaxel Regimens Appear Equally Effective in Metastatic Breast Cancer, However, Combination is More Toxic

Doxorubicin and docetaxel, either in combination or as sequential or alternating therapies, appear to be equally effective in treating metastatic breast cancer, however, the combination of the 2 drugs appears to be the most toxic, with a risk of cardiac events.

Dr S. Cresta, of the Department of Oncology, Instituto Nazionale Tumori, Milan, Italy, and colleagues initiated a study of 2 non-cross-resistant drugs, doxorubicin and docetaxel, in patients with metastatic breast cancer. The objective was to evaluate the merits and limits of different schedules of administering these 2 drugs.

A total of 123 women, ages 18 to 70 years, with metastatic breast cancer (Stage 4 disease) were enrolled into this phase 2, open-label, randomised trial. They were divided into 3 treatment groups: docetaxel and doxorubicin either given in combination (60 mg/m² of each drug); in an alternating schedule, or in sequence; i.e., 100 mg/m² doxorubicin and 75 mg/m² doxorubicin, every 3 weeks for a maximum 8 eight cycles.

The primary objective was to determine the rate of complete response with each schedule. Secondary objectives included overall response, time to progression, survival and safety.

Since febrile neutropaenia is a particular concern with docetaxel, a second randomisation was done in which patients in each arm were allocated to receive prophylactic ciprofloxacin or no antibiotic therapy.

A total of 110 patients were eligible for admission. Of these, 53 patients had prior adjuvant therapy, including anthracyclines (16 patients). Visceral involvement was present in the majority of patients. Liver metastases were present in 46%, 43%, and 40% of patients on the combined drug regimen, the alternating and sequential schedules, respectively.

All 3 schedules demonstrated good therapeutic activity. In an intention-to-treat analysis, the overall response was 63% with the combination, 52% with the alternating regimen, and 61% with the sequential regimen. Corresponding rates of complete response were 15%, 14% and 11% respectively, with no statistically significant difference between treatments. Survival in the 3 groups did not differ.

Giving the 2 drugs in combination proved to be the most toxic, with cardiotoxicity related to the higher exposure to doxorubicin. Congestive heart failure occurred in 10% of patients receiving the combination. Treatment was discontinued related to adverse effects in 14 patients: 2 on the alternating regimen, 5 on sequential treatment, and 7 on the combination.

Grade 4 neutropaenia was common in all study arms (81%), and together with febrile neutropaenia, was significantly more frequent with the combination.

Ciprofloxacin did not reduce the incidence of febrile neutropaenia: the control arm showed an incidence of 6% febrile neutropaenia whereas the incidence was 14% with ciprofloxacin.

All 3 dosage schedules for docetaxel and doxorubicin were feasible for women with metastatic breast cancer, concluded Dr. Cresta. However, the combination was the least in favour because of its significantly greater haematologic and cardiac toxicity. Whether these findings may apply to women with operable breast cancer awaits the results of 3 major ongoing studies.

This study was supported by a grant from Aventis-Antony, France.

Ann Oncol 2004;15:433-9.

E-Mail this DGReview to a colleague

To print, use this version