Improved safety profile of nolatrexed dihydrochoride in the ETHECC Trial when compared to the safety of the phase II program in unresectable hepatocellular carcinoma (uHCC)

4260 Background: We compare the patients' safety profile in the Phase III ETHECC (E) trial to the combined patient safety profile of patients treated with nolatrexed dihydrochloride (THYMITAQ) (T) in the 3 uHCC Phase II studies. T is a folate analogue inhibitor of Thymidylate Synthase (TS) that binds directly to the folate site of TS. Methods: The hematological (H) toxicities (anemia, neutropenia, and thrombocytopenia) and non-hematological (NH) toxicities (mucositis, nausea, vomiting, diarrhea, and rash) data are compared between 117 T patients from the E trial (following the second independent Data Safety Monitoring Board [DSMB] in May 2003) and 129 T patients from the Phase II studies in HCC (Studies 008 [Stuart et al]; 014 [Mok et al]; 015 [ASCO 2003]). Results: There is a reduction in the number of patients experiencing grade 3–4 H and NH toxicities in the E© trial compared to the Phase II data: mucositis by 50%; nausea by 67%; vomiting by 50%; diarrhea by < 50% (with no grade 4 in E); rash by 92%; and neutropenias by 36%. The percentages of febrile neutropenia (13.7%) and infection (5.1%) were also low in the E trial. The percentages of grade 3–4 thrombocytopenia (characteristic of HCC) were about the same without increased association of severe bleeding events (6.0%). Conclusions: The reduction in the number of patients experiencing NH toxicities is a direct result of the supportive care measures incorporated in the E trial. These include the prophylactic use of antiemetics for nausea and vomiting, the use of antihistamines for rash, as well as adequate hydration and oral measures for the treatment of mucositis. Overall, there is an improved outcome in the safety profile in the Phase III study as a result of intensification and active management of expected toxicities. With newer and more effective means of mitigating (or ameliorating) symptoms, these toxicities will become easily controlled. An update with safety data from the third Data Safety Monitoring Board (DSMB) in January 2004 will be communicated at the meeting. No significant financial relationships to disclose.