Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer

Abstract

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m À2 ) plus FA (500 mg m À2 , 2-h infusion) followed by 5-FU (2000 mg m À2 , 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39 -69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2 -26.2 months), median survival is 11.4 months (95% CI, 8.0 -14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9 -9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil

“…Although the detailed mechanism for oxaliplatin-induced TS gene downregulation needs to be further elucidated, our result is concordant with two previous reports (Raymond et al, 2002;Yeh et al, 2004), which indicated that oxaliplatin could downregulate TS in cancer cells and thus potentiate the efficacy of 5-FU. As oxaliplatin and 5-FU have been shown to be highly synergistic not only in preclinical models (Raymond et al, 1997) but also in subsequent clinical trials (Rothenberg et al, 2003;Chao et al, 2004;Lordick et al, 2005;Schippinger et al, 2005;Cavanna et al, 2006), our data provide important information regarding why the combination of oxaliplatin and 5-FU results in better objective response than single use alone.…”

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

“…In contrast, oxaliplatin, which had improved the efficacy of 5-fluorouracil (5-FU) treatment in colorectal cancer, was extensively studied in GC. Following promising phase II study results [22][23][24], oxaliplatin was compared with cisplatin in two randomized controlled trials. Both studies were designed to prove the non-inferiority of oxaliplatin compared with cisplatin.…”

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

“…In 2005, there were approximately 400 000 new cases and 300 000 deaths from gastric cancer (Yang, 2006). There is currently no established standard regimen for advanced gastric cancer; however, biweekly oxaliplatin plus 5-fluorouracil (5-FU) and folinic acid (FOLFOX) was well tolerated and yielded median survival times of 9.6 -11.4 months in five phase II studies (Louvet et al, 2002;Al-Batran et al, 2004;Chao et al, 2004;De Vita et al, 2005;Lordick et al, 2005). Considerable published evidence suggests that interindividual variation in response to 5-FU results from variations in the thymidylate synthase (TS) mRNA expression levels of the tumour (Longley et al, 2003).…”