A New Practical Desensitization Protocol for Oxaliplatin-Induced Immediate Hypersensitivity Reactions: A Necessary and Useful Approach.

BACKGROUND AND OBJECTIVE: Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol. METHODS: We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags. RESULTS: Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria. CONCLUSIONS: Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice.

Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model.

We have previously synthesized a new cationic liposome that displays high efficiency and low toxicity, 3 beta[l-ornithinamide-carbamoyl] cholesterol (O-Chol), using solid-phase synthesis. In this study, O-Chol was applied to in vitro and in vivo models of ovarian cancer. Intraperitoneal gene delivery for peritoneal disseminated ovarian cancer in nude mice was achieved using a stable chloramphenicol acetyl transferase (CAT)-expressing ovarian cancer cell line (OV-CA-2774/CAT), which allowed us to quantify the exact tumor burden of organs. When luciferase and beta-galactosidase genes were used as reporter genes, O-Chol showed better efficiency than other commercial transfection reagents such as lipofectin, lipofectAMINE, DC-Chol, and FuGENE 6, both in vitro and in vivo. Moreover, the transfection efficiency of this new cationic lipid reagent remained high in serum-containing medium and under serum-free conditions. Furthermore, in vivo transfection with O-Chol showed high levels of gene expression specific to peritoneal tumor cells. Consequently, the O-Chol:DNA lipoplex appears to offer potential advantages over other commercial transfection reagents because of (1) its higher level of gene expression in vitro and in vivo; (2) its reduced susceptibility to serum inhibition; and (3) its highly selective transfection into tumor cells. These results suggest that the O-Chol:DNA lipoplex is a promising tool in gene therapy for patients with peritoneal disseminated ovarian cancer.