Loading…
Phase I Study of Escalating Doses of Edatrexate in Combination with Paclitaxel in Patients with Metastatic Breast Cancer
Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this c...
Saved in:
Published in: | Clinical cancer research 1999-02, Vol.5 (2), p.275-279 |
---|---|
Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h
paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of
edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this
novel combination.
Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts
of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise
dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The
initial dose level of edatrexate was 180 mg/m 2 ; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m 2 ). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m 2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication.
The MTD of edatrexate was reached at the 350 mg/m 2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m 2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m 2 dose level and also required dose reduction, establishing the MTD as 350 mg/m 2 . Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported
grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m 2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m 2 . No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel.
In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an
overall response rate of 48% (95% confidence interval, 27â69%). All of the responses were seen in patients who had not received
prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients
went on to receive high-dose chemotherapy treatment with stem cell support.
The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The
MTD of edatrexate was 350 |
---|---|
ISSN: | 1078-0432 1557-3265 |