Introduction: DM-CHOC-PEN is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 – guanine and via oxidative stress. The aims of this clinical trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), pharmacokinetics (PK) of DM-CHOC-PEN and monitor for clinical responses.
Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21-days to patients with advanced cancer; melanoma (n=3), colorectal CA (n=3), breast (n=3) and glioblastoma multiforme (n=6). The trial included patients with advanced cancer +/- CNS involvement. The starting dose was 39 mg/m2 with escalations to date up to 111 mg/m2.
Results: Twenty-six (26) patients have been treated. The MTD was 2-tiered and defined as 85.8 mg/m2 for patients with liver involvement and 98.7 mg/m2 for patients without liver abnormalities. The most common adverse effects were fatigue (n=2), liver dysfunction – elevated bilirubin (Gr-3, n=3; Gr-2, n=1), ALT/AST (Gr-2, n=3), alk phos (Gr-2, n=3) and an allergic reaction (Gr-2, n=1). Three (3) patients with liver metastasis demonstrated hyperbilirubinemia (Gr-3 SLT) – 2 at the 98.7 mg/m2 and one (1) at the 111 mg/m2 levels Five (5) additional patients with liver disease have been treated at 85.8 mg/m2 level without toxicity.
Conclusions: DM-CHOC-PEN is safe at the presented dose levels and has a favorable PK profile. Eight (8) patients had responses or significant PFS, including 6 with CNS involvement. A Phase II trial has begun in patients with primary brain cancer and brain metastases from melanoma, breast cancer and lung cancer.
Patient Care: We hope to expand the chemotherapeutic resources available to patients with brain tumors by introducing a new novel agent. We also determined maximum-tolerated dose (MTD), safety, dose-limited toxicities (DLTs), and pharmacokinetics.
Learning Objectives: By the conclusion of this session, participants should be able to 1) Describe the importance of therapeutic dosages in novel treatment modalities, 2) Discuss, in small groups DM-CHOC-PEN as an expanding treatment options for patients with tumor cells, 3) Identify an effective treatment with DM-CHOC-PEN, 4) Discuss the need for safety monitoring of novel chemotherapeutic agents