Phase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors.

Purpose: This phase I study assessed the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SJG-136, a sequence-specific DNA cross-linking agent, in patients with advanced cancer.

Experimental Design: In schedule A, seven patients received escalating doses of SJG-136 (6, 12, 24, and 48 μg/m(2)) daily for 5 of 21 days. Blood samples were collected for PK analysis on days 1 and 5 of cycle 1.

A phase I trial of irinotecan alternating with epirubicin in patients with advanced malignancies.

Objectives: This phase I study was conducted to evaluate the combination of irinotecan, a topoisomerase I inhibitor, with epirubicin, a topoisomerase II inhibitor, when administered sequentially on a once-every-three week basis.

Methods: Irinotecan was administered at doses ranging from 100 to 150 mg/m(2) intravenously over 90 minutes, 24 hours before epirubicin, in doses from 30 to 60 mg/m(2), every 3 weeks. Toxicity assessments were performed weekly.