Combination of bevacizumab (A) and pegylated-liposomal doxorubicin (PLD) (PLD-A) in sarcoma (SAR)

Abstract

9556 Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis (AG) in many tumors including SAR. A has demonstrated efficacy in several common solid tumors. Because of the known efficacy of PLD in SAR and the presumed importance of VEGF in SAR, we have treated SAR patients with PLD-A. It is possible that the addition of A to PLD might alter the toxicity profile. To our knowledge, the toxicities of this combination have not been previously described. Methods: To better define the toxicity of the combination of PLD-A in SAR, we reviewed our experience with PLD-A in patients with SAR treated between 2004 and 2005. Results: We identified 12 patients with SAR treated with PLD-A at our institution. There were 5 men and 7 women, with a median age of 43.5 years (range 27–57). Nine patients initiated therapy with PLD on a 28 day interval at a median dose of 45 mg/m2 (range 45–50), and 3 on a 14 day interval at a dose of 22.5 mg/m2, in combination with A at 5 mg/kg every 2 weeks. A median of 3 cycles was given (range 2–9). Standard CALGB response and NIH common toxicity criteria were used. Dose delay was required in 3 patients for the second cycle, and dose reduction was required in 5 patients by cycle 3. Of the 10 patients starting with monthly PLD, 6 were changed to q 2 week PLD by cycle 4. Mucositis and skin toxicity were the dose limiting toxicities (DLT) in 9/12 patients, and myelosuppression was the DLT in 1/12 patients. Conclusions: This report describes the toxicity profile of PLD-A in 12 patients with SAR. The toxicities observed were similar to those seen with PLD alone, however, there was a suggestion that these toxicities may be more pronounced with the addition of A, though this appears to vary among patients. Since VEGF is important for wound healing, the known effects of A on this process may contribute to more skin and mucosal toxicity of PLD at a given dose. Future studies of PLD-A should consider the potential of increased mucosal and skin toxicity, and the use of q2week PLD to allow more control over toxicity is suggested. [Table: see text]