A phase 1 trial of motexafin gadolinium and docetaxel for advanced solid tumors

Abstract

3171 Background: Motexafin gadolinium (MGd) is a redox mediator that selectively targets tumor cells, producing reactive oxygen species. In preclinical models, MGd enhances the activity of several chemotherapy drugs including taxanes. Based on this, a multi-center Phase 1 study with MGd and docetaxel was carried out in patients (pts) with advanced solid tumors, with normal bone marrow, hepatic and renal function. Experimental design: Cohorts of 3–6 pts were treated with MGd, starting at 2.5 mg/kg weekly with docetaxel starting at 30 mg/m2on a weekly X 3 schedule every 28 days. The primary objective was to determine the maximum tolerated dose (MTD) of the combination on this schedule and the dose limiting toxicities (DLT). Results: Eight pts were treated at MGd (2.5- 5mg/kg weekly) along with docetaxel (30mg/m2). The MGd was infused over 0.5h, 30 minutes prior to docetaxel (given IV over 0.5h). There were 8 males with a median age of 61yrs (range 54–76). Diagnoses were NSCLC (3); SCLC (2); Gastric (1); bladder (1); and penile (1). (No of pts in parenthesis) Pts had had a median of 3 prior chemotherapy regimens (range 1–5); 3 pts had had prior radiation. Two pts received 1.5 cycles. At dose level (DL) 1, toxicities >/= 2 were fatigue, diarrhea, leucopenia, neutropenia, hyperglycemia, elevated APTT, seen in 3 pts. At DL 2 (MGd 5.0 mg/kg with docetaxel 30 mg/m2), 1 pt had a DLT (gr 3 rash). Other toxicities >/= gr 2 at DL 2 were nausea, vomiting, diarrhea, fatigue, and dehydration in 2 pts. Data on the last 3 pts is pending. Accrual is ongoing to determine the MTD. Conclusion: MGd in combination with weekly docetaxel is feasible and preliminary results show that there were no gr 4 toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacyclics