COLUMBUS, OhioA phase II study presented at the San Antonio
symposium has shown that weekly gemcitabine (Gemzar) combined with
monthly 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
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.