A Dose Escalation Study of Pegylated Liposomal Doxorubicin (Caelyx) in Combination with Capecitabine (Xeloda) in Patients with Refractory Solid Tumors

Abstract

Objective: Pegylated liposomal doxorubicin (PLD) and capecitabine (CAP) have separately shown significant antitumor activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Patients and Methods: Fifteen patients with histologically confirmed inoperable solid neoplasms were enrolled. The patients’ median age was 65 years, 10 were male, and 12 had a performance status score (WHO) of 0–1. PLD was administered on day 1 as a 1-hour intravenous infusion at escalated doses ranging from 35 to 40 mg/m². CAP was administered on days 1–14 per os, at escalated doses ranging from 1,600 to 1,800 mg/m², given as two daily divided doses. Treatment was repeated every 3 weeks. Results: At the dose of PLD 40 mg/m² and CAP 1,800 mg/m², all 3 enrolled patients presented DLTs [2 patients grade 3 palmar-plantar erythrodysesthesia (PPE) and 1 patient grade 3 asthenia] and thus, the recommended MTD for future phase II studies is PLD 40 mg/m² and CAP 1,700 mg/m². A total of 57 treatment cycles were administered. Grade 2/3 neutropenia complicated 9 (17%) cycles and 1 patient was hospitalized for febrile neutropenia. There was no septic death. The main nonhematologic toxicity was PPE grade 2 in 3 (19%) patients and grade 3 in 4 (27%). PPE was the reason of treatment interruption for 3 patients. Other toxicities were mild and easily manageable. Two patients (16%) with partial response suffering from gastric cancer and 5 patients with (42%) stable disease were observed among 12 evaluable patients. Conclusions: The results of this phase I study demonstrate that PLD and CAP can be combined at clinically effective and relevant doses. However, PPE is a common side effect and further investigation is warranted to define its precise role in the treatment of solid malignancies.