A dose escalation study of pegylated liposomal Doxorubicin (caelyx) in combination with capecitabine (xeloda) in patients with refractory solid tumors.

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/m(2). CAP was administered on days 1-14 per os, at escalated doses ranging from 1,600 to 1,800 mg/m(2), given as two daily divided doses. Treatment was repeated every 3 weeks.

RESULTS

At the dose of PLD 40 mg/m(2) and CAP 1,800 mg/m(2), 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/m(2) and CAP 1,700 mg/m(2). 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.