Adriamycin Bests Taxol as Therapy for Advanced Breast Cancer

HAMBURG—In previously un-treated women with advanced breast cancer, doxorubicin (Adriamycin) yields a higher response rate and longer progression-free survival than does paclitaxel (Taxol), according to the results of a randomized crossover trial conducted by the EORTC and presented at the Ninth European Cancer Conference (ECCO 9).

“Doxorubicin as first-line treatment of advanced breast cancer followed by paclitaxel should be preferred to the reverse sequence,” said Study Coordinator R. Paridaens of the University of Leuven (Belgium).

However, Dr. Paridaens warned, “the increased antitumor activity of doxorubicin is achieved at the expense of greater hematologic, gastrointestinal, and cardiac toxicity.”

The EORTC investigators randomized 331 chemotherapy-naïve patients to receive either paclitaxel, 200 mg/m² over 3 hours every 3 weeks, or doxorubicin, 75 mg/m², over 5 to 15 minutes every 3 weeks to a maximum cumulative dose of 525 mg/m².

Crossover to the alternative regimen for second-line treatment was mandatory for women who exhibited progressive disease during the first seven courses and was optional for women who later showed progressive disease.

Significant Difference in Response

“We had a significant difference in the objective response rate to first-line treatment—25% with paclitaxel and 41% with doxorubicin,” Dr. Paridaens reported.

The curves for progression-free survival showed a major and significant advantage in favor of the doxorubicin group, he said. Median progression-free survival was 7.6 months for women who received first-line doxorubicin therapy, compared with 4.1 months for their paclitaxel-treated counterparts.

Among women who were resistant to doxorubicin and crossed over to second-line paclitaxel, the tax-ane produced a partial response rate of 13% and was associated with progressive disease in 46% of cases.

In contrast, Dr. Paridaens noted, partial responses were observed in 30% of paclitaxel-resistant patients who were crossed over to doxorubicin, and progressive disease was seen in only 16% of this group. “There is no cross-resistance between the two drugs, whatever the sequence of administration,” he said.

For overall survival, first-line doxorubicin was always superior, although the P-value did not reach significance, Dr. Paridaens said. The duration of survival was 18.4 months for patients starting with doxorubicin, compared with 15.2 months for those who initially received paclitaxel.

Adverse Effects

Doxorubicin was linked with a higher incidence of vomiting (13% vs 2% with paclitaxel), stomatitis (15% vs 1%), and cardiotoxicity (5% vs 1%), and with a slightly though not significantly higher rate of documented infections. Neurotoxicity, on the other hand, was more common during taxane treatment (9% versus 0%).

Quality of life, as assessed by the Rotterdam Symptom Checklist and the EORTC QLQ-C30, did not differ significantly between the two treatment arms. After three cycles of doxorubicin treatment, patients were experiencing more side effects but reporting less bone pain and better overall pain control.

A particularly interesting finding in this study, Dr. Paridaens said, was that baseline global quality of life was a good predictor of later survival.