Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer

Background: MCC-465 is an immunoliposome-encapsulated doxorubicin (DXR). The liposome is tagged with polyethylene glycol (PEG) and the F(ab')(2) fragment of human monoclonal antibody GAH, which positively reacts to >90% of cancerous stomach tissues, but negatively to all normal tissues. In preclinical studies, MCC-465 showed superior cytotoxic activity against several human stomach cancer cells compared with DXR or DXR-incorporated PEG liposomes. The main purpose of this trial was to define the maximum tolerated dose (MTD), dose limiting toxicity (DLT), recommended phase II dose and pharmacokinetics (PK) of MCC-465. Patients and methods: Patients with metastatic or recurrent stomach cancer were eligible for entry. The initial dose was 6.5 mg/m(2). MCC-465 was administered as a 1-h infusion every 3 weeks and the treatment continued for up to six cycles. Results: Twenty-three patients received a total of 62 cycles at the 6.5-45.5 mg/m(2) dose level. DLTs were myelosuppression and appetite loss at the 45.5 mg/m(2) dose level. Other toxicities were mild. Neither palmar-plantar erythrodysesthesia nor cardiotoxicity was observed. Acute reactions related to infusion were observed commonly in 16 patients over the entire dose range. While no antitumor response was observed, stable disease (SD) was observed in 10 out of 18 evaluable patients. The pharmacokinetic study showed a similar AUC and C-max to Doxilo(R). Conclusion: MCC-465 was well tolerated. The recommended dose for a phase II study of MCC-465, for a 3-week schedule, is considered to be 32.5 mg/m(2) in an equivalent amount of DXR.