First-in-man phase I study assessing the safety and pharmacokinetics of a 1-hour intravenous infusion of the doxorubicin prodrug DTS-201 every 3 weeks in patients with advanced or metastatic solid tumours.

Purpose: DTS-201 is a doxorubicin (Dox) prodrug that shows encouraging data in experimental models in terms of both efficacy and safety compared with conventional Dox. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose (RD) for clinical phase II studies and to assess potential anticancer activity of the compound.

Experimental Design: DTS-201 was administered as a 1-hour infusion every 3 weeks in eligible patients with advanced solid tumours according to common clinical phase I criteria.

Preclinical toxicity, toxicokinetics, and antitumoral efficacy studies of DTS-201, a tumor-selective peptidic prodrug of doxorubicin.

Purpose: There is a clear clinical need for cytotoxic drugs with a lower systemic toxicity. DTS-201 (CPI-0004Na) is a peptidic prodrug of doxorubicin that shows an improved therapeutic index in experimental models. The purpose of the current study was to complete its preclinical characterization before initiation of phase I clinical trials.

Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell).

Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attractive candidates to minimize many of the limitations observed for a broad range of cytotoxic molecules. The studies reported here characterized the in vitro and in vivo efficacy of a range of Vectocell peptides conjugated to doxorubicin through different linkers.

Thimet oligopeptidase (EC 3.4.24.15) activates CPI-0004Na, an extracellularly tumour-activated prodrug of doxorubicin.

CPI-0004Na is a tetrapeptidic extracellularly tumour-activated prodrug of doxorubicin. The tetrapeptide structure ensures blood stability and selective cleavage by unidentified peptidase(s) released by tumour cells. The purpose of this work was to identify the enzyme responsible for the first rate-limiting step of CPI-0004Na activation, initially attributed to a 70 kDa acidic (pI=5.

CPI-0004Na, a new doxorubicin prodrug, reduces growth of 3LL-H61 carcinoma lung metastases in C57BI/6 mice.

The ETAP concept (Extracellularly Tumor-Activated Prodrug) is a new approach developed to overcome the lack of selectivity and the side effects responsible for the limited efficacy of chemotherapeutic agents. CPI-0004Na, a doxorubicin (Dox) prototype prodrug of this type, is less toxic than free Dox and showed increased efficacy against subcutaneous human tumor xenografts. The aim of this study was to assess the efficacy of the prodrug vs Dox (given ip) at their maximal tolerated dose (MTD) for this administration schedule (129.