Phase I trial of irinotecan and epirubicin in patients with advanced solid tumors

Abstract

2120 Background: Irinotecan (I) and Epirubicin (E) have broad anti-tumor activity and different mechanisms of action. A Phase I clinical trial was initiated to define the maximum tolerated dose (MTD) of this combination. Methods: Patients who had received at least 1 prior chemotherapy regimen for advanced solid tumors were eligible. Patients in the first cohort received I 250 mg/m2 IV and E 50 mg/m2IV every 21 days. No hematopoetic growth factor support was permitted. Due to dose-limiting neutropenia in cohort 1, the doses were de-escalated to I 200 mg/m2 IV and E 35 mg/m2IV every 21 days. Results: 11 patients were enrolled, 6m/5f. The median age was 62 years (range 34–82). There was 1 each of breast, colon, endometrial, gastric, lung, ovarian, and unknown primary cancers. There were 2 each of melanoma and pancreatic cancer. The patients were heavily pre-treated, with a median of 3 (range 2–9) prior chemotherapy regimens. Three patients in the first cohort had dose-limiting neutropenia, which prevented escalation. A subsequent 6 patients were treated at dose-level -2, and three patients had dose-limiting neutropenia as well. One patient with lung cancer had a partial response of 3.5 months duration. Another patient with colon cancer had stable disease for 5 months. Conclusions: In this heavily pre-treated population, it was not possible to determine the MTD. Clinical activity was noted in lung and colon cancer. Future studies should focus on less heavily pre-treated patients and should consider cytokine support. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer