Phase I/II Pharmacokinetic Study of Pemetrexed and Epirubicin in Patients with Locally Advanced or Metastatic Breast Cancer

• Published in: Clinical breast cancer Vol. 7; no. 11; pp. 861 - 866
• Main Authors: Paridaens, Robert, Dirix, Luc, Dumez, Herlinde, Prové, Annemie, Wildiers, Hans, Alvarez, Ana, Oliveira, Celia Tosello, Latz, Jane, Simms, Lorinda, Melemed, Allen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2007
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Bone Neoplasms - secondary; Breast Neoplasms - drug therapy; Disease Progression; Dose reduction; Dose-Response Relationship, Drug; Drug Administration Schedule; Epirubicin - administration & dosage; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Left ventricular ejection fraction; Liver Neoplasms - secondary; Lung Neoplasms - secondary; Middle Aged; Neoplasm Metastasis; Neutropenia; Obstetrics and Gynecology; Pemetrexed; Pharmacokinetics; Treatment Outcome; Pharmacokinetics; Left ventricular ejection fraction; Dose reduction; Neutropenia
• ISSN: 1526-8209; 1938-0666
• DOI: 10.3816/CBC.2007.n.051

Abstract Background Pemetrexed and epirubicin are each active in patients with advanced/metastatic breast cancer (MBC). This phase I/II study evaluated these drugs as a combination regimen. Patients and Methods Women with locally advanced or MBC were enrolled. Pemetrexed 400–600 mg/m2 and epirubicin 60–90 mg/m2 were administered on day 1 every 21 days. The recommended phase II dose was evaluated in a 2-stage design. Results Phase I enrolled 34 patients and evaluated 5 dose levels. Dose-limiting toxicities were neutropenia and febrile neutropenia. Patients received a median of 7.5 cycles (range, 1–8 cycles), and promising efficacy (partial response [PR], 32%; stable disease [SD], 50%) was observed. Pharmacokinetics of pemetrexed was unchanged when combined with epirubicin. Selected phase II regimen (pemetrexed 600 mg/m2 and epirubicin 75 mg/m2 ) was administered to 22 patients (median, 4.5 cycles; range 1–13 cycles). Five patients experienced a PR (23%), and 10 experienced SD (46%). This response was below the predefined efficacy requirements for subsequent enrollment, and accrual was stopped. Median time to progression was 5.3 months (95% CI, 3.1-8.9 months), and median time to treatment failure was 3.5 months (95% CI, 2.6-5.9 months). Conclusion The regimen is safe but cannot be recommended as first-line chemotherapy in advanced breast cancer because of the low response rate.