Phase I study of pegylated liposomal doxorubicin (CA) and docetaxel (T) bimonthly in the first-line treatment of metastatic breast cancer (MBC): The CAT regimen

Abstract

818 Background: The combination of doxorubicin (Dox) and docetaxel [Taxotere (T)] is one of the most active chemotherapeutic regimens in breast cancer. Pegylated liposomal doxorubicin [Caelyx (CA)] has a more favorable pharmacokinetic and toxicity (tox) profile, with comparable efficacy as monotherapy in MBC, compared with conventional Dox. We conducted a phase I study to determine the safety, feasibility, and dose limiting tox (DLT) of the CAT regimen, substituting CA for Dox in combination with T. Methods: Escalating doses of CA (30–35 mg/m2, day 1) were administered as a 30-min infusion every 4 weeks with bimonthly administration of T (40–50 mg/m2, day 1 & 15) in a 1H infusion, without initial growth factor support. DLT was defined as febrile neutropenia, prolonged neutropenia, or grade (gr.) 3 to 4 non-hematologic tox that occurred during the 1st cycle (Cy). The combination was considered acceptable if not interrupted for tox and if the received/planned dose-intensity (DI) was ≥90% during 6 scheduled Cy. Results: 13 patients (pts) with MBC and no prior chemotherapy (CT) for metastatic disease were enrolled. Dose level 1, with CA and T at doses of 30 and 50 mg/m2, respectively, induced DLT (prolonged gr. 4 neutropenia) at Cy 1 in 1/5 pts. Two pts had early progression, and CT was considered unacceptable in the 2 remaining pts (early termination - pulmonary embolism and DI <90% - repeated delays from prolonged neutropenia). Dose level 2, with CA and T at doses of 35 and 40 mg/m2, respectively, induced DLT (gr. 3 palmar-plantar erythrodysesthesia [PPE]) in 1/8 pts at Cy 1. Out of the 7 remaining pts at dose level 2, 6 completed 6 Cy with DI >90%. The most severe tox observed per pt were gr. 4 neutropenia (3 pts), gr. 2 PPE (3 pts), gr. 2 alopecia (2 pts), and gr. 2 mucositis (1 pt). Four pts experienced course delays and needed G-CSF support, and 1 additional pt had a dose reduction at Cy 6. No decrease of LVEF was observed. Conclusions: The administration of CA (35 mg/m2, d1) with T (40 mg/m2, d1 & 15) every 4 weeks is feasible. The CAT regimen is associated with acceptable and easily manageable tox. It merits further evaluation in MBC, a phase II study is planned. No significant financial relationships to disclose.