Diagnosis and treatment of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), characterized by a translocation between the promyelocytic leukemia gene (PML) on chromosome 15 and the retinoic acid receptor-alpha (RARalpha) gene on chromosome 17, has become a model for targeted treatment of cancer. Advances in our understanding of the fundamental biology of this disease have led to the development of tools for diagnosis, monitoring of minimal residual disease, and detection of early relapse. Differentiation therapy with all-trans retinoic acid in combination with chemotherapy has significantly improved survival in patients with APL.

Phase I and pharmacokinetic study of the novel oral cell-cycle inhibitor Ro 31-7453 in patients with advanced solid tumors.

Purpose: To determine maximum tolerated dose, pharmacokinetics (PK), and safety of Ro 31-7453, a novel, oral cell-cycle inhibitor.

Patients And Methods: Using an accelerated dose-escalation schedule, 48 patients with advanced solid tumors were treated with doses of Ro 31-7453 ranging from 25 to 800 mg/m(2)/d given for 4 consecutive days, every 3 weeks. The total daily dose was taken as a single dose (schedule A) or divided into two equal doses taken 12 hours apart (schedule B).

Effect of arsenic trioxide on QT interval in patients with advanced malignancies.

Purpose: Arsenic trioxide is an effective treatment for patients with acute promyelocytic leukemia (APL) who have relapsed from or are refractory to all-trans-retinoic acid and anthracycline chemotherapy. Since arsenic can prolong the QT interval and lead to torsade de pointes, a life-threatening ventricular arrhythmia, this retrospective analysis was conducted to determine the degree of QT prolongation in patients treated with arsenic trioxide.

Patients And Methods: Clinical data and serial ECGs from 99 patients with advanced malignancies who received 170 courses of arsenic trioxide in either a phase I or phase II investigational study were reviewed.

Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies.

Purpose: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacodynamics (PD) of the proteasome inhibitor bortezomib (previously known as PS-341) in patients with refractory hematologic malignancies.

Patients And Methods: Patients received PS-341 twice weekly for 4 weeks at either 0.40, 1.

Established practice in the treatment of patients with acute promyleocytic leukemia and the introduction of arsenic trioxide as a novel therapy.

First-line therapy for patients with newly diagnosed acute promyelocytic leukemia (APL) has been established in a series of randomized clinical trials. Remission induction and consolidation are based on the differentiation agent, all-trans retinoic acid (ATRA), and anthracycline-based chemotherapy. Maintenance therapy is also based on ATRA and may involve additional chemotherapy.