Randomized, Multicenter, Open-Label Study of Oxaliplatin Plus Fluorouracil/Leucovorin Versus Doxorubicin As Palliative Chemotherapy in Patients With Advanced Hepatocellular Carcinoma From Asia

Abstract

Although the study did not meet its primary end point, the trend toward improved OS with FOLFOX4, along with increased PFS and RR, suggests that this regimen may confer some benefit to Asian patients, but an OS benefit cannot be concluded from these data.

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…In a randomized phase III study, FOLFOX showed improved ORR (8.2% vs. 2.7%, P=0.02) and improved PFS (median PFS: 2.9 vs. 1.8 months, P≤0.001) with a non-significant trend for increased OS (median OS: 6.4 vs. 5.0 months, P=0.07) compared with single agent doxorubicin (38). The most common grade 3 to 4 adverse events from FOLFOX were neutropenia (30.6%), leukocytopenia (8.7%), thrombocytopenia (7.7%) and anemia (4.9%) in the study.…”

Systemic therapy for advanced hepatocellular carcinoma: an update

“…Grade 3/4 adverse effects were similar in both groups. Although this trial demonstrated improved OS following FOLFOX4 treatment, sorafenib-the current standard of care for advanced HCC-was not used as a comparison, thus limiting the applicability of these findings (46).…”

“…Combination chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) was compared with doxorubicin monotherapy in an Asian trial (46). Median OS was 6.40 months with FOLFOX4 and 4.97 months with doxorubicin (HR, 0.80; 95% CI, 0.63 to 1.02; P=0.07); median PFS was 2.93 vs. 1.77 months (HR, 0.62; 95% CI, 0.49-0.79; P<0.001).…”

Drug Development for Hepatocellular Carcinoma: Knowing the Past Helps to Understand the Future

“…The study is based on a multicenter randomized clinical trial, known as the EACH study, conducted from March 2007 to May 2009 [10].The EACH study was carried out in Southeast Asian countries, from which patients with a confirmed diagnosis of advanced HCC were randomized in a 1:1 ratio into one of two chemotherapy regimens, namely, FOLFOX4 (oxaliplatin, leucovorin, 5-fluorouracil) or doxorubicin. The results of the whole EACH study have already been published in full in 2013 [10].…”

“…The study is based on a multicenter randomized clinical trial, known as the EACH study, conducted from March 2007 to May 2009 [10].The EACH study was carried out in Southeast Asian countries, from which patients with a confirmed diagnosis of advanced HCC were randomized in a 1:1 ratio into one of two chemotherapy regimens, namely, FOLFOX4 (oxaliplatin, leucovorin, 5-fluorouracil) or doxorubicin. The results of the whole EACH study have already been published in full in 2013 [10]. In summary, the study failed to meet its primary objective of improvement in overall survival (6.4 months in the FOLFOX4 arm vs. 5.0 months in the doxorubicin arm; p 5 .07) despite an improvement in progression-free survival favoring the FOLFOX4 regimen [10].…”