Endostar in combination with modified FOLFOX6 as an initial therapy in advanced colorectal cancer patients: a phase I clinical trial.

PURPOSE

Endostar is a recombinant human endostatin with antiangiogenic properties that has been useful in treating a wide range of cancers and shows promise for use in combination treatment for advanced colorectal cancer. This study aimed to evaluate the drug safety and tolerability of continuous intravenous infusion (CIV) of endostar in combination with modified FOLFOX6 (mFOLFOX6) as an initial therapy in advanced colorectal cancer patients.

METHODS

This was a single-center, single-arm, open, dose-escalation study in patients with advanced colorectal cancer at Fudan University Shanghai Cancer Center between August 2010 and January 2012. A total of 21 patients were included. Standard dosage of mFOLFOX6 was used. CIV endostar commenced on day 4 to day 14 ascending from 7.5 to 15, 30, 45, 60, and 75 mg/m(2)/day. Primary outcomes were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CIV endostar in combination with mFOLFOX6. Secondary outcomes were pharmacokinetic parameters. Physical examination, performance status, standard blood tests and electrocardiograms were performed.

RESULTS

MTD was 75 mg/m(2)/day. Adverse events included leucopenia (n = 17, 81 %), neutropenia (n = 12, 57.1 %), anemia (n = 5, 23.8 %), anorexia (n = 6, 28.6 %) and constipation (n = 4, 19.0 %). One patient with an allergic reaction stopped chemotherapy. Two patients stopped endostar treatment, one with level 3 ventricular premature beat (DLT at 15 mg/m(2)/day) and one with a level 1 ventricular arrhythmia (30 mg/m(2)/day). The main ECG changes were ST-segment and T wave changes. Exposure to endostar and CIV dose was linear between 7.5 and 30 mg/m(2)/day (R (2) = 0.974).

CONCLUSIONS

Endostar in combination with mFOLFOX6 was generally safe and well tolerated.