Scheduled administration of low dose irinotecan before gemcitabine in the second line therapy of non-small cell lung cancer: a phase II study.

We had previously demonstrated that low dose irinotecan (CPT-11) leads to increased accumulation of cells in S-phase and shows a therapeutic synergy with S-phase specific chemotherapy such as gemcitabine and 5-fluorouracil. In this phase II study, our objectives were to evaluate the tolerability and activity of low dose CPT-11 followed 24 h later by gemcitabine as second line therapy in patients with metastatic non-small cell lung cancer (NSCLC). CPT-11 (60 mg/m) was administered 24 h before gemcitabine (1000 mg/m) on days 1, 2, 8, and 9 every 3 weeks.

A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors.

Purpose: We conducted a phase I study to determine the recommended dose of selenomethionine (SLM) in combination with irinotecan that consistently results in a protective plasma selenium (Se) concentrations > 15 microM after 1 week of SLM loading.

Experimental Design: A 3-3 standard escalation design was followed. SLM was given orally twice daily (BID) for one week (loading) followed by continuous once daily (QD) dosing (maintenance).

A phase I study of capecitabine and a modulatory dose of irinotecan in metastatic breast cancer.

Purpose: There is a need for chemotherapy regimens active against anthracycline- and taxane-refractory breast cancer. Data from preclinical and pilot studies performed at Roswell Park Cancer Institute (RPCI) suggested that when irinotecan (IRN) is given with 5-fluorouracil (5-FU) efficacy is affected by the sequence of drug administration. Pretreatment with IRN 24 h before 5-FU increased the number of tumor cells in S-phase and the antitumor activity in a preclinical system.

A phase I pharmacokinetic and pharmacodynamic study of s-3304, a novel matrix metalloproteinase inhibitor, in patients with advanced and refractory solid tumors.

Purpose: Matrix metalloproteinases (MMP) play a fundamental role in cancer development and progression. S-3304 is a potent, orally active, noncytotoxic inhibitor of MMPs, primarily MMP-2 and MMP-9, that prolongs survival in mice xenografts and is well tolerated in healthy volunteers.

Experimental Design: The aims of this phase I clinical trial were to determine the maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and intratumoral MMP inhibitory activity of single-agent S-3304 in advanced and refractory solid tumors.

A phase I pharmacokinetic and pharmacodynamic study of intravenous calcitriol in combination with oral gefitinib in patients with advanced solid tumors.

Purpose: In preclinical models, calcitriol and the tyrosine kinase inhibitor gefitinib are synergistic and modulate extracellular signal-regulated kinase (Erk) and Akt pathways. Therefore, we conducted a phase I study of calcitriol and gefitinib to determine the maximum tolerated dose (MTD) of this combination.

Experimental Design: Calcitriol was given i.