In contrast to CPT, CZ48 incubated in vitro with human plasma and studied in vivo maintains a substantial closed lactone ring concentration in the plasma. It appears to act as a pro-drug. The removal of the side chain by endogenous esterases liberates the active drug, CPT. Malignant cells have a high esterase content and are rapidly transforming the pro-drug into the active parent drug. Preclinical studies suggest retention of anti-cancer activity and reduction in toxicity, probably because the pro-drug in the systemic circulation has no or little activity. Therefore, delivery of higher concentrations of closed lactone ring CPT analog inside the tumor cells should potentiate the anti-tumor activity. This study offers an opportunity to evaluate this hypothesis.