5-Fluorouracil, folinic acid, epidoxorubicin and cisplatin (FLEP) combination chemotherapy in advanced measurable gastric cancer. A phase II trial of the Spanish Cooperative Group for Gastrointestinal Tumor Therapy

Villar-Grimalt, A; Abad, Albert; Antón-Torres, Antonio; Belon, J.; Dorta, J.; Trés, A.; Camps, C.; Fonseca, E.; Massutí, B.; Aranda, Enrique; Blanco, Esperanza J. Carcache de; Paredes, M. García de; Hernández, J. J. Sánchez; Garcı́a-Conde, J; Dı́az-Rubio, Eduardo

doi:10.1093/oxfordjournals.annonc.a058660

Cited by 15 publications

(8 citation statements)

References 19 publications

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“…Nonetheless, this combination is clearly active in patients with advanced gastro-oesophageal cancer with an overall response rate of 38% in a limited number of evaluable patients. Whilst this is lower than the phase II response rates initially obtained with infusional 5-FU in combination with epirubicin and cisplatin (Findlay et al, 1994;Zaniboni et al, 1995), it is similar to that obtained with other platinum-containing regimens (Elliott et al, 1990;Sparano et al, 1990;Lacave et al, 1991;Cervantes et al, 1993;Bajetta et al, 1994Bajetta et al, , 1998Taal et al, 1994;Kondo et al, 1996;Cheng et al, 1998) or with ECF in randomized studies (Webb et al, 1997). The median survival of 9.9 months compares with 8.9 months obtained with ECF and between 7 and 11 months with other cisplatin-based therapies (Lacave et al, 1991;Cervantes et al, 1993;Bajetta et al, 1999Bajetta et al, , 1998Kondo et al, 1996;Cheng et al, 1998).…”

Section: Discussionsupporting

confidence: 57%

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et al. 2000

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Gastric adenocarcinoma has a poor prognosis, accounting for 10 000 deaths per year in the UK. Although its incidence is declining, it remains the second most common tumour world-wide and the fourth commonest cancer in Europe. At presentation around 30% of patients have metastatic disease and a further 30% have locally advanced disease penetrating the serosal surface of the stomach or directly invading adjacent organs. With locally advanced disease, curative surgery is only possible in a minority of patients and recurrent disease affects 80% of patients within 5 years of potentially curative surgery. Therefore the prognosis remains poor with an overall survival of around 20% at 5 years (Allum et al, 1989).Combination chemotherapy results in a significant survival advantage in patients with advanced gastric cancer compared with best supportive care in randomized clinical trials. High response rates may be obtained with the use of protracted venous infusional 5-fluorouracil (5-FU), cisplatin and epirubicin -the ECF regimen (Findlay et al, 1994). In an initial study with this regimen, an overall response rate of 71% and a complete response rate of 12% were observed. These encouraging results have been confirmed in two subsequent studies, with overall response rates of around 60% and with complete responses occurring in around 10% of patients (Highley et al, 1994;Zaniboni et al, 1995). In a multi-centre randomized study, ECF resulted in significantly better response rate (45%) and median survival (8.9 months), with significantly less toxicity compared to the FAMtx regimen (Webb et al, 1997). Consequently the ECF regimen is considered the treatment of choice for advanced adenocarcinoma of the oesophagus and stomach by many clinicians in the UK.This regimen, however, requires protracted venous infusion of 5-FU through a Hickman catheter, which is associated with significant morbidity. The most common problems encountered are thrombosis and sepsis requiring line removal in up to 15% of patients (Webb et al, 1997). Consequently, replacing the continuous infusion of 5-FU by a drug with a related mechanism of action would overcome the need for inserting a Hickman catheter and its associated morbidity. As inhibition of thymidylate synthase (TS) is an important mechanism of action of infusional 5-FU, one such strategy is to combine epirubicin and cisplatin with a specific TS inhibitor. TS catalyses the reductive methylation of deoxyuridylate (dUMP) to thymidylate (TMP), the rate-limiting step in the synthesis of deoxythmidine triphosphate (TTP). TTP is the only nucleotide specifically required for DNA synthesis and has been postulated as an ideal target for anticancer drugs.Raltitrexed (tomudex) is a quinazolone-based, water-soluble anti-folate, which is extensively and efficiently poly-glutamated. The poly-glutamates are 100 times more potent inhibitors of TS than the parent drug and are retained intra-cellularly allowing a A dose-finding study of raltitrexed (tomudex) with cisplatin and epirubicin in advanced gastro-oesoph...

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Section: Discussionsupporting

confidence: 57%

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et al. 2000

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“…The EORTC study showed the FAMTX (5-FU/adriamicyn/methotrexate) was superior to FAM (5-FU/adriamycin/mitomic) in RR (41% versus 9%) and survival (42 versus 29 weeks). 7,9 A number of studies have found that PELF or similar combinations are more active and have other advantages over FAMTX [21][22][23] with a similar proportion of toxicities and toxic deaths. 21 Subsequently, a series of studies demonstrated that ECF (epirubicin/cisplatin/5-FU) led to longer survival than FAMTX (median OS 8.9 versus 5.8 months) 11,18 and a recent review of palliative chemotherapy for advanced gastric cancer confirmed that ECF currently represents one of the most effective regimens for advanced gastric cancer and among the newer combinations, irinotecan-or taxane-based regimens have given promising results.…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin in Combination With 5-Fluorouracil (5-FU) and Leucovorin (LV) in Patients With Metastatic Gastric Cancer (MGC)

Cavanna¹,

Artioli²,

Codignola³

et al. 2006

American Journal of Clinical Oncology

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“…The important contribution of the 5-FU schedule has been emphasized by the results of a recently reported study in which a regimen consisting of the same drugs as ECF, but with 5-FU given as a bolus and the addition of folinic acid, produced inferior results. 33 In conclusion, ECF appears to be an effective, well tolerated regimen for advanced EG cancer. It produces symptomatic response in the majority of patients, with no negative impact in QL.…”

Section: Discussionmentioning

confidence: 82%

Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for esophagogastric adenocarcinoma: Response, toxicity, quality of life, and survival

Bamias

Hill

Cunningham

et al. 1996

Cancer

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5-Fluorouracil, folinic acid, epidoxorubicin and cisplatin (FLEP) combination chemotherapy in advanced measurable gastric cancer. A phase II trial of the Spanish Cooperative Group for Gastrointestinal Tumor Therapy

Abstract: The FLEP regimen is an active combination in advanced gastric cancer with moderate toxicity that warrants further testing in a phase III trial.

Cited by 15 publications

References 19 publications

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Oxaliplatin in Combination With 5-Fluorouracil (5-FU) and Leucovorin (LV) in Patients With Metastatic Gastric Cancer (MGC)

Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for esophagogastric adenocarcinoma: Response, toxicity, quality of life, and survival

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