TY - JOUR
T1 - A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with metastatic breast carcinoma
AU - Esteva, Francisco J.
AU - Rivera, Edgardo
AU - Cristofanilli, Massimo
AU - Valero, Vicente
AU - Royce, Melanie
AU - Duggal, Anil
AU - Colucci, Philippe
AU - DeJager, Robert
AU - Hortobagyi, Gabriel N.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - BACKGROUND. The objective of the current study was to determine the antitumor activity, safety, and pharmacokinetic (PK) profile of exatecan mesylate in patients with anthracycline-resistant and taxane-resistant, metastatic breast carcinoma. METHODS. All patients had clinical evidence of metastatic breast carcinoma; disease resistance or progression after chemotherapy that included anthracyclines and taxanes; no prior chemotherapy with camptothecin derivatives; and bidimensionally measurable disease. The starting dose of exatecan mesylate was either 0.5 mg/m2 per day or 0.3 mg/m2 per day, depending on prior chemotherapy exposure. PK blood samples were collected from each patient during the first course of therapy. RESULTS. Thirty-nine patients received a total of 172 courses of therapy (median, 4 courses; range, 1-16 courses). Three patients (7.7%) had a partial response, and 20 patients (51.3%) had either a minor response or stable disease. Approximately 20% of patients had stable disease for 6 months or longer. The median time to disease progression was 3 months, and the median survival was 14 months. The most frequent severe adverse event was neutropenia. The most frequent severe (Grade 3-4) nonhematologic toxicities were fatigue, nausea, headache, myalgia, constipation, emesis, and paresthesias in 28%, 10%, 10%, 8%, 8%, 5%, and 5% of patients, respectively. Exatecan mesylate displayed linear PK characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 1.4 L per hour per m2, 12 L/m2, and 8 hours, respectively. CONCLUSIONS. Exatecan mesylate had moderate activity in patients with anthracycline-refractory and taxane-refractory, metastatic breast carcinoma. The toxicity profile of exatecan mesylate was acceptable, and it appeared to have linear PK characteristics on the basis of multiple dose administration.
AB - BACKGROUND. The objective of the current study was to determine the antitumor activity, safety, and pharmacokinetic (PK) profile of exatecan mesylate in patients with anthracycline-resistant and taxane-resistant, metastatic breast carcinoma. METHODS. All patients had clinical evidence of metastatic breast carcinoma; disease resistance or progression after chemotherapy that included anthracyclines and taxanes; no prior chemotherapy with camptothecin derivatives; and bidimensionally measurable disease. The starting dose of exatecan mesylate was either 0.5 mg/m2 per day or 0.3 mg/m2 per day, depending on prior chemotherapy exposure. PK blood samples were collected from each patient during the first course of therapy. RESULTS. Thirty-nine patients received a total of 172 courses of therapy (median, 4 courses; range, 1-16 courses). Three patients (7.7%) had a partial response, and 20 patients (51.3%) had either a minor response or stable disease. Approximately 20% of patients had stable disease for 6 months or longer. The median time to disease progression was 3 months, and the median survival was 14 months. The most frequent severe adverse event was neutropenia. The most frequent severe (Grade 3-4) nonhematologic toxicities were fatigue, nausea, headache, myalgia, constipation, emesis, and paresthesias in 28%, 10%, 10%, 8%, 8%, 5%, and 5% of patients, respectively. Exatecan mesylate displayed linear PK characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 1.4 L per hour per m2, 12 L/m2, and 8 hours, respectively. CONCLUSIONS. Exatecan mesylate had moderate activity in patients with anthracycline-refractory and taxane-refractory, metastatic breast carcinoma. The toxicity profile of exatecan mesylate was acceptable, and it appeared to have linear PK characteristics on the basis of multiple dose administration.
KW - Breast neoplasms
KW - Camptothecin
KW - Clinical trials
KW - Exatecan mesylate
KW - Pharmacokinetics
KW - Phase II
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U2 - 10.1002/cncr.11557
DO - 10.1002/cncr.11557
M3 - Article
C2 - 12942555
AN - SCOPUS:0042889292
SN - 0008-543X
VL - 98
SP - 900
EP - 907
JO - Cancer
JF - Cancer
IS - 5
ER -