Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors

Abstract

Methods: aEuro,As part of a phase I study of S-CKD602 and phase I and II studies of NL-CKD602, the percent decreases in ANC and monocytes at their nadir were calculated. After S-CKD602, the amount of CKD-602 recovered in urine was measured. Results: aEuro,For S-CKD602 in patients < 60 years, the percent decrease in ANC and monocytes were 43 +/-+/- 31 and 58 +/-+/- 26%, respectively (P == 0.001). For S-CKD602 in patients >= a parts per thousand yen60, the percent decrease in ANC and monocytes were 41 +/-+/- 31 and 45 +/-+/- 36%, respectively (P == 0.50). For NL-CKD602 (n == 42), the percent decrease in ANC and monocytes were similar (P > 0.05). For S-CKD602, the relationship between the percent decrease in monocytes and CKD-602 recovered in urine was stronger in patients < 60 (R<SU2</SU == 0.82), compared with patients >= a parts per thousand yen60 (R<SU2</SU == 0.30). Conclusions: aEuro,Monocytes are more sensitive to S-CKD602, compared with neutrophils, and the increased sensitivity is related to the liposomal formulation, not CKD-602. These results suggest that monocytes engulf S-CKD602, which causes the release of CKD-602 from the liposome and toxicity to the monocytes, and that the effects are more prominent in patients < 60.