Phase I trial of M2ES, a novel polyethylene glycosylated recombinant human endostatin, plus gemcitabine in advanced pancreatic cancer.

Pancreatic cancer is one of the most lethal and resistant to treatment of solid tumors. Combination therapies with various types of drugs against pancreatic cancer have been extensively investigated. Endostatin is a potent endogenous inhibitor of angiogenesis, which may be administered in combination with various chemotherapeutic agents in the treatment of several types of cancer. To the best of our knowledge, this phase I trial was the first clinical study to determine the tolerance, safety and efficacy of M2ES, a novel polyethylene glycosylated recombinant human endostatin, administered concurrently with full-dose gemcitabine in patients with inoperable, locally advanced or metastatic pancreatic adenocarcinoma. A total of 16 patients were treated with gemcitabine (1,000 mg/m(2) on days 1, 8 and 15) and M2ES (5-45 mg/m(2) on days 1, 8, 15 and 21) of each 28-day cycle. In 15 evaluable patients, the stable disease rate (SDR) was 40% (95% CI: 11.9-68.1%). In particular, a 75% SDR was observed in 3 out of 4 patients with a M2ES dose level of 7.5 mg/m(2). The most noticeable M2ES-related adverse events observed during the trial were grade 2 liver function abnormalities (6.3%) and grade 1 skin rash (6.3%). No dose-limiting toxicity was observed in any patients from all the dose levels. Therefore, there was no increased toxicity associated with the addition of M2ES to gemcitabine and this combination was well tolerated.