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To help settle the controversy over the optimal first-line chemotherapy regimen for MBC, Katsumata et al evaluated treatment with AC followed by D upon progression (AC to D; n = 146); D followed by AC upon progression (D to AC; n = 147); and alternating AC and D (AC-D; n = 148).
At 5 years (June 2004), the study found no significant differences between the three approaches in time to progression and time to treatment failure, although it did note a trend for improved survival in both experimental arms. However, at an updated analysis in December 2004 (5.5 years), a significant difference emerged in overall survival favoring both D to AC as well as alternating AC-D, Dr. Katsumata said.
The Japan Clinical Oncology Group 9802 trial (JCOG 9802) found some survival advantage to using docetaxel (Taxotere) first-line, as well as alternating doxorubicin/cyclophosphamide (AC) with docetaxel (D), over standard AC followed by docetaxel in the treatment of hormone-refractory metastatic breast cancer (MBC). However, time to progression was similar, Noriyuki Katsumata, MD, National Cancer Center Hospital, Tokyo, reported at the 41st Annual Meeting of the American Society of Clinical Oncology.
The three regimens were as follows:
At the time of failure or progression after the front-line chemotherapy, the patient was crossed over to another therapy in arm AC and D, and for arm AC-D they received the same regimen again.
Completion rates for the regimens were as follows: AC to D, 68%; D to AC, 76%; and AC-D, 76%. Disease progression occurred in 24%, 18%, and 15%, respectively.
In a subset analysis, patients who received prior adjuvant anthracyclines demonstrated a significantly better survival with first-line AC, compared with the other arms (P = 0.033). In patients who received no prior adjuvant anthracyclines, front-line D was significantly superior (P = 0.033).
There were no differences in quality-of-life measurements between the arms. Tolerability was similar in all three arms; grade 4 neutropenia, however, was more frequent in the D to AC and alternating AC-D treatment arms.
Dr. Katsumata concluded, “There is no benefit for docetaxel or alternating AC-D in time to failure, but docetaxel and alternating AC-D tend to be superior in response rate and overall survival to the standard AC regimen. Because of the possibility of a survival benefit, first-line treatment with docetaxel should be evaluated in longer follow-up.”
In the discussion period, it was noted that the doses of AC used in this study as well as the docetaxel dose were somewhat lower than are often used.
Andrew Seidman, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, commented, “Because of the availability of many other active chemotherapy agents, the re-initiation of an alternating regimen would not reflect a choice that most of us would make in practice.” He also said the use of a one-sided log rank test to determine P value was not optimal.
Katsumata N, Minami H, Aogi K, et al. Phase III trial of doxorubicin (A)/cyclophosphamide (C) (AC), docetaxel (D), and alternating AC and D (AC-D) as front-line chemotherapy for metastatic breast cancer (MBC): Japan Clinical Oncology Group trial (JCOG 9802). Paper presented at the 41st Annual Meeting of the American Society of Clinical Oncology; May 13–17, 2005; Orlando, Fla. Abstract 521.