• exatecan mesylate;
  • camptothecin;
  • clinical trials;
  • Phase II;
  • pharmacokinetics;
  • breast neoplasms



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.


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.


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.


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. Cancer 2003;98:900–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11557