C. Wasserheit et al., PHASE-II TRIAL OF PACLITAXEL AND CISPLATIN IN WOMEN WITH ADVANCED BREAST-CANCER - AN ACTIVE REGIMEN WITH LIMITING NEUROTOXICITY, Journal of clinical oncology, 14(7), 1996, pp. 1993-1999
Purpose: A phase II study of paclitaxel and cisplatin in patients with
advanced breast cancer was performed to determine the objective respo
nse rate and make further observations about the toxicity of this regi
men. Patients and Methods: Patients were required to have histological
ly proven adenocarcinoma of the breast with no more than one chemother
apeutic treatment for advanced disease. Treatment consisted of paclita
xel 200 mg/m(2) administered as a 24-hour intravenous (IV) infusion fo
llowed by cisplatin 75 mg/m(2) IV. Patients received granulocyte colon
y-stimulating factor (G-CSF) 5 mu g/kg subcutaneously on day 3 until W
BC recovery. Cycles were repeated every 21 days, Patients continued to
receive therapy until disease progression or unacceptable toxicity. R
esults: Forty-four patients entered the trial. Forty-two patients were
assessable for response. Nineteen patients (43%) had no prior chemoth
erapy and 41 had no chemotherapy for metastatic disease. The median nu
mber of cycles administered per patient was five (range, one to seven)
. There were five complete responses (CRs) (11.9%) and 17 partial resp
onses (PRs) (40.5%), with an overall response rate of 52.4% (95% confi
dence interval [Cl], 36.4% to 68.0%). Nine patients had stage III dise
ase. The response rate for this group was 66.7% (95% Cl, 33.0% to 92.5
%), with three CRs and three PRs. Among 35 patients with stage IV dise
ase, there were two CRs and 14 PRs, with an overall response rate of 4
8.5% (95% Cl, 30.8% to 66.5%). Overall, the median response duration w
ets 10.6 months. Thirty patients (68%) developed transient grade 4 neu
tropenia. Cumulative neuropathy was the major dose-limiting toxicity.
After five cycles of chemotherapy, 96% of patients had at least grade
1 neurotoxicity and 52% of held at least grade 2 neurotoxicity, One pa
tient had a toxic death after cycle 1 of therapy. Conclusion: The comb
ination of paclitaxel and cisplatin as first-line chemotherapy for wom
en with advanced breast cancer is an active regimen. However, the cumu
lative neurotoxicity was significant and dose-limiting in the majority
of patients.