Objectives: Paclitaxel and doxorubicin are among the most active chemotherapeutic agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a more favorable pharmacokinetic and toxicity profile than the free drug. We conducted a phase I study to determine the maximum tolerated doses (MTD) and the dose limiting toxicities (DLT) of the combination administered every 2 weeks in patients with advanced solid tumors. Patients and Methods: Treatment consisted of escalating doses of Caelyx (12.5–17.5 mg/m2) administered as a 30-min intravenous infusion on day 1 and paclitaxel (90–115 mg/m2) as a 3-hour intravenous infusion on day 2 every 2 weeks without growth factor support. One cycle was considered as the administration of two consecutive treatments in 28 days. Twenty-six patients with histologically confirmed advanced stage solid tumors have been enrolled. Treatment was first-line treatment for 38% of patients, second-line for 31% and third-line for 31%. Results: The DLT were evaluated during the first 4 weeks of treatment (2 treatment administrations) and consisted in all but one case of grade 2–3 neutropenia resulting in treatment delay. One patient died of cardiac arrest 1 day after the first treatment. A total of 86 cycles have been administered with only 1 episode of febrile neutropenia. Hematologic toxicity was generally mild. Only 1 patient at the first and another at the highest dose level developed grade 4 neutropenia. At the highest dose level, 3 of 6 patients developed grade 3 neutropenia. Grade 4 anemia or grade 3–4 thrombocytopenia was not observed. Non-hematologic toxicity included grade 2–3 nausea/vomiting in 10%, grade 2–4 diarrhea in 7% and grade 2–3 neurotoxicity in 8% of cycles. Mucositis grade 3 complicated 1 cycle. Palmar-plantar erythrodysesthesia grade 2–3 was observed in 3 patients and was the reason for treatment discontinuation in 1 patient. Cardiotoxicity as the development of congestive heart failure or more than 10% reduction in left ventricular ejection fraction was not observed. The most common non-hematologic toxicity was grade 2–3 asthenia complicating 31% of the cycles. Among 18 evaluable patients, 1 complete and 4 partial responses were observed primarily in patients with breast cancer. The MTD which are the recommended doses for further use in phase II trials were Caelyx 15 mg/m2 on day 1 and paclitaxel 115 mg/m2 on day 2 administered every 2 weeks. Conclusion: The administration of Caelyx and paclitaxel every 2 weeks is a feasible regimen and is associated with acceptable toxicity.

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