Troxatyl™ is the first dioxolane nucleoside with potent in vitro and in vivo antitumor activity. This cytosine analog is a DNA polymerase inhibitor and complete DNA chain terminator. It undergoes cellular uptake with prolonged retention of the phosphorylated metabolites. Troxatyl™ is not a substrate for cytidine deaminase and is the only L-isomer nucleoside analog with anti-tumor activity. In a Phase I study of Troxatyl™ in patients (pts) with primary refractory or relapsed acute leukemia, mucositis and hand-foot syndrome were the dose limiting toxicities. (Giles el al Abstract 4231 ASH 1999). The recommended single agent dose was defined as 8 mg/m2/day daily for 5 days. Preliminary results are presented for 13 pts ( 10 female and 3 male, median age:52 years; range:23-80), with CMLBP treated at this dose as part of an ongoing Phase II study. Prior therapy for CML chronic phase included hydroxyurea alone (1 pt), alpha interferon-based therapy (7 pts), homoharringtonine (HHT) ( 1 pt), allogeneic Stem Cell Transplantation (SCT) ( 1 pt). Eleven pts had received and failed one or more prior therapy for CMLBP including topotecanbased therapy (5 pts), allogeneic SCT (3 pts), 6-thioguanine (1 pt), HHT (2 pts), mitoxantrone/ ara-C (1 pt), STI (5 pts), donor lymphocyte infusions (1 pt), 2-CDA/cyclophosphamide/ VP16U pt),hCVXD(l pt),clofarabine/decitabine(l pt),liposomalDaunorubicin/ara-C(l pt), CVAD (1 pt). Toxicities included: Grade 2 skin rash - 5 pts; hand-foot syndrome: Grade 2-4 pts, Grade 3-3 pts; Grade 2 mucositis - 1 pt; Grade 4 mucositis - 2 pts. Three patients were converted to 2nd chronic phase with a median duration of 10 months (range 9-16). Two pts had early deaths from progressive disease and two others are too early to assess. Four patients have received two or more courses of therapy. Troxatyl(tm) has activity in heavily pretreated patients with CMLBP and merits further study in first line as a single agent and in combination.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology