Phase I Trial of Irinotecan (CPT-11) and Gemcitabine in Patients With Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) and the principal toxicities of irinotecan and gemcitabine in patients with surgically unresectable or metastatic solid tumors.
• Determine if the principal toxicities and MTD of this combination regimen are affected by drug sequencing in this patient population.
• Determine the potential for gemcitabine to alter the pharmacokinetic characteristics when administered with irinotecan in these patients.
• Describe the influence effected by varying the administration sequence of this combination regimen in this patient population.
• Obtain preliminary data regarding efficacy of this combination regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive irinotecan IV over 90 minutes followed by gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) is reached, patients receive subsequent doses of the inverse sequence of the combination drugs until a new MTD is determined.

Cohorts of 3-6 patients receive escalating doses of irinotecan and gemcitabine until the MTD is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.