COLUMBUS, OhioA phase II study presented at the San Antonio symposium has shown that weekly gemcitabine(Drug information on gemcitabine) (Gemzar) combined with monthly docetaxel(Drug information on docetaxel) (Taxotere) is an effective second-line therapy for metastatic breast cancer.
The responses that we saw were very striking in that they were calculated on a rigorous intent-to-treat basis and excluded patients who had nondurable remissions, reported Leslie Laufman, MD, clinical assistant professor of medicine, Ohio State University. With that kind of a rigorous cal-culation, we came up with a 59% response rate (3 complete responses and 16 partial responses in 32 patients).
The response rate was similar for all populations of patients, whether they had truly anthracycline-refractory disease or whether they had received their chemotherapy in the remote past (see Table). So it is a very solid number, she said.
To be eligible for the study, patients had to have biopsy-proven metastatic breast cancer with a measurable lesion, failure of one prior chemotherapy regimen (in either the adjuvant or metastatic disease setting), and no prior taxanes or gemcitabine. Almost all the patients had received prior treatment with an anthracycline and an alkylating agent, Dr. Laufman added.
Patients were given gemcitabine at a weekly dose of 800 mg/m² on days 1, 8, and 15, and docetaxel monthly on day 1 at a dose of 100 mg/m² The cycle was repeated every 4 weeks, and assessments were completed after the second and fourth cycles. Those patients who responded had the option of continuing treatment beyond four cycles.
Thirty-nine patients have been enrolled; 32 patients, with a mean age of 52, were evaluable at the time of the presentation.
The most significant toxicity with this trial was grade 4 neutropenia, which affected all of the patients at some point. But that did not translate into a significant problem with severe infections, Dr. Laufman said. Other than the neutropenia, there were no major toxicities, she added.
The neutropenia was a surprising finding because we did a phase I trial of this regimen in patients with all types of diagnoses and did not have so much trouble. Thats how we came up with these doses in the first place, she said. She indicated that the prior chemotherapy, either the anthracycline or the alkylating agent, may be the source of the problem.
Because of the neutropenia, there were several dosage reductions or dose deletions, particularly the day 8 gemcitabine dose. Those patients who had the docetaxel dose decreased to 75 mg/m2 were able to receive the scheduled dose of gemcitabine. And I think the 75 mg/m² dose of docetaxel would probably be a very reasonable way to use this regimen in the future, Dr. Laufman said.