Clinical trial of MCC-465, a doxorubicin encapsulated in PEG-immunoliposome, in patients with metastatic stomach cancer

Abstract

MCC-465 is an immunoliposome-encapsulated doxorubicin (DXR). The liposorne is tagged with polyethylene glycol (PEG) and the F (ab′) 2 fragment of a human monoclonal antibody named GAH which positively reacts to more than 90% of cancerous stomach tissues, though negative to all normal tissues. In pre-clinical studies, MCC-465 showed superior cytotoxic activity against several human stomach cancer cells compared to DXR or DXR-incorporated PEG-liposomes. Phase I trials ware carried out to define the maximum tolerated dose, dose limiting toxicity, recommended phase II dose and the pharmacokinetics of MCC-465. Patients(pts) with metastatic or recurrent stomach cancer were eligible for entry to phase I trial. MCC-465 was administered as an 1 hr infusion every 3 weeks and the treatment continued for up to 6 cycles. Twenty-three pts received a total of 62 courses at the 6.5 to 45.5 mg/m2 dose level. DLTs were myelosuppression and appetite loss at the 45.5 mg/m2 dose level. Other toxicities were mild. Neither palmar-plantar erythrodysesthesia (PPE) nor cardiotoxicity was observed. Acute reactions related to infusion were observed commonly in 16 pts in all the dose ranges. While no antitumor response was observed, NC was observed in 10 out of 18 evaluable pts. The pharmacokinetic study showed a similar AUC and Cmax to Doxil. MCC-465 was well tolerated. The recommended dose for phase I of MCC-465 for a three-week schedule was considered to be 32.5 mg/m2. © 2004, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.