Background: The present study was designed with the aim of evaluating the tolerability and activity of pegylated liposomial doxorubicin (PLD) in combination with weekly docetaxel as first line treatment of advanced breast cancer.
Patients and methods: Fifty-seven patients entered the study. PLD was administered at escalating doses starting from 30 mg/m2, on day 1; docetaxel was administered at the fixed dose of 35 mg/m2 on days 2 and 9. A cycle of therapy consisted of 21 days.
Results: The MTD was achieved at the dose of 40 mg/m2 of PLD, being febrile neutropenia and palmar-plantar-erythrodisesthesia (PPE) the dose-limiting toxicities (DLTs), so that the fixed dose of PLD for the Phase II study was 35 mg/m2. Forty-two consecutive patients received treatment at the established dose for a total of 194 cycles: among these, three patients were withdrawn for severe allergic reaction at the first administration of PLD. Hematological toxicity was moderate, the most common grade 1-3 non-hematological toxicities were stomatitis and PPE, occurring in 20 (47.5%) and 16 (38%) patients, respectively. No cardiac toxicity was recorded. According to the intent to treat analysis a major objective response was observed in 59.5% of patients (95% CI, 43.3-74.4%), with a median time to progression of 9 months and an estimated overall survival at 18 months of 62%.
Conclusion: The combination of PLD and weekly docetaxel is an effective first-line therapy for patients with advanced breast cancer. PPE and mucositis are the most relevant side effects of such a combination.