Second‐line chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) in patients with advanced small bowel adenocarcinoma after failure of first‐line platinum‐based chemotherapy

Abstract

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. First-line platinum-based chemotherapy is active in patients with advanced SBA, but data regarding second-line chemotherapy are lacking. The aim of this study was to evaluate the efficacy and tolerability of fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) as second-line chemotherapy in patients with advanced SBA. METHODS: We analyzed all consecutive patients who received second-line chemotherapy with FOLFIRI among 93 patients with advanced SBA included from 1996 to 2008 in a previous retrospective multicenter study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method. Cox models were applied for multivariate analyses. RESULTS: Among 51 patients who received second-line chemotherapy, 28 patients (male, 57%; median age, 54 years; metastatic disease, 96%) were treated with FOLFIRI after progression (n ¼ 24) or limiting toxicity (n ¼ 4) to first-line FOLFOX (n ¼ 19) or LV5FU2-cisplatin (n ¼ 9). Grade 3-4 toxicity was observed in 48% of patients (grade 3-4 neutropenia, 37%). After a median follow-up of 21.5 months, all patients had tumor progression, and 22 patients died. Objective response rate was 20%, and disease control rate was 52%. Median PFS and OS were 3.2 and 10.5 months, respectively. No clinical, biological, or tumor characteristics were associated with PFS or OS by multivariate analysis. CONCLUSIONS: Second-line chemotherapy with FOLFIRI produced disease control in half of patients with advanced SBA after failure with first-line platinum-based chemotherapy. Nevertheless, the short median PFS warrants the evaluation of other treatments including targeted therapies.

Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma

“…Several retrospective studies have indicated that chemotherapy prolongs overall survival in patients with advanced small intestinal adenocarcinomas, but there is no standard frontline regimen owing to a lack of randomized trials. 5,25 Patients with advanced small intestinal adenocarcinomas are often treated with the same chemotherapy regimens as patients with advanced colorectal cancers or gastric cancers, especially 5-fluorouracil (FU) or 5-FU-based schedules. 9 The combination of 5-FU and a platinum-based agent has been considered more effective than other regimens such as oxaliplatinbased chemotherapy.…”

“…25,26 The main challenge for the near future is to identify molecular markers involved in small bowel carcinogenesis that predict chemosensitivity, and thus to improve survival. 5 Overman et al 27 observed that a high proportion of small intestinal adenocarcinomas express both EGFR and vascular endothelial growth factor (VEGF), suggesting that these patients may benefit from therapeutic strategies targeting EGFR and VEGF. Targeted therapies such as monoclonal antibodies against VEGF or EGFR combined with chemotherapy have already exhibited significant efficacy in metastatic colorectal cancers.…”

“…3 Lymph node metastasis and distal location (jejunum and ileum) are the most important independent prognostic factors. 4 As a result of the nonspecific nature of presenting clinical manifestations and the lack of effective tools for exploring the small intestine, small intestinal adenocarcinomas are usually diagnosed at an advanced stage, 5 at which chemotherapy can only prolong overall survival. The cytotoxic agents used are generally the same as those used to treat patients with advanced colorectal cancers, and include oral or intravenous fluoropyrimidines, platinum and irinotecan.…”

“…The cytotoxic agents used are generally the same as those used to treat patients with advanced colorectal cancers, and include oral or intravenous fluoropyrimidines, platinum and irinotecan. 5 Unfortunately, there is no standard treatment and the place of new targeted therapies has still to be defined. 1 Moreover, the number of tumor samples collected remains limited because of the low incidence of the disease, which explains the lack of information regarding somatic genetic alterations that occur during small intestinal carcinogenesis.…”

Adverse drug reaction: a comparative analysis of protocols used for treatment of colorectal cancer

“…14,17 Os principais fatores relacionados a ocorrência destes desfechos negativos são o número de ciclos de tratamento, 18 o uso de quimioterapia prévia, 19 a existência de comorbidades, o performance status, a presença de metástases e o uso do esquema FOLFOX. 20,21 As toxicidades gastrointestinais podem ser exacerbadas em tratamentos com uso de oxaliplatina favorecendo o aparecimento de sintomas como diarreia, estomatite, dispepsia ou boca seca podendo interferir na qualidade de vida do paciente. Cabe destacar, a relevância dos episódios de diarreia graus 3/4, no qual, levam a sérias complicações como desidratação, íleo paralítico, hipocalemia, obstrução intestinal, acidose metabólica ou até mesmo toxicidade renal.…”