Clinical use of molecular targeted agents for primary small bowel adenocarcinoma: A multicenter retrospective cohort study by the Osaka Gut Forum

Abstract

Abstract. Primary small bowel adenocarcinoma (SBA) is a rare cancer for which effective treatment strategies have not yet been established. The results of previous retrospective studies suggest that chemotherapy contributes to a longer survival time in patients with SBA. However, there are few case reports about the efficacy of molecular targeted agent-containing chemotherapy for SBA. In the present study, the treatment and follow-up data of patients with SBA who received chemotherapy with or without molecular targeted agents were retrospectively analyzed. Each patient was treated in one of ten hospitals participating in the Osaka Gut Forum between April 2006 and March 2014. The following factors were evaluated: Age, sex, Eastern Cooperative Oncology Group performance status (PS), tumor location, tumor differentiation, chemotherapy regimen, resection of primary tumor, tumor biomarker expression, distant metastasis, best response under chemotherapy, time to disease progression, subsequent treatments, survival status and treatment toxicity. A total of 27 patients (17 males and 10 females; mean age, 63.4 years old; range, 36-83 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. The median overall survival time was 14.8 months (range, 2-58 months). A univariate analysis revealed a PS of 0 (P=0.0228) and treatment with platinum-based chemotherapy (P=0.0048) were significant factors for an improved prognosis. An age-adjusted multivariate analysis also revealed that a platinum-based regimen was a significant positive prognostic factor (P=0.0373). Molecular targeted agents were administered to 8 patients, for whom it was their first-or second-line therapy. Among the 17 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P= 0.0255) and treatment with bevacizumab (P= 0.0121) were significant positive prognostic factors. Toxicities higher than Grade 3 occurred in 8/27 patients with SBA; however, serious side effects due to the molecular targeted agents were not experienced. The results of the present study indicate that chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA.

Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

“…We recently demonstrated that bevacizumab in combination with platinum-based chemotherapy is effective and well-tolerated for metastatic SBA (mSBA) [11], consistent with other reports [12][13][14][15]. Furthermore, Legue et al [15] reported that bevacizumab is effective for metastatic ileal adenocarcinoma (mIA), but it has remained unclear whether bevacizumab is also effective for metastatic duodenal and jejunal adenocarcinoma (mDJA).…”

“…We then investigated the PFS and the OS among mDJA patients with high or low VEGF-A expression. The PFS was signi cantly longer in patients with high VEGF-A expression (median [95% CI] 9 months [4][5][6][7][8][9][10]) than in those with low VEGF-A expression (5 months [1][2][3][4][5][6][7], P = 0.018; Figure 1a) and the OS tended to be longer in those with high VEGF-A expression (20 months [15][16][17][18][19][20][21][22][23][24]) than in those with low VEGF-A expression (7 months [5][6][7][8][9][10][11][12][13][14], P = 0.059; Supplemental Figure 3a). In the Bevacizumab+ Platinum Group, the PFS was signi cantly longer in patients with high VEGF-A expression (26 months [15-]) than in those with low VEGF-A expression (5 months [1][2][3][4][5][6][7][8][9], P = 0.001; Figure 1b) and the OS tended to be longer in patients with high VEGF-A expression than in those with low VEGF-A expression (P =...…”

Bevacizumab in metastatic small-bowel adenocarcinoma: A systematic review and meta-analysis

“…Notably, although median OS, PFS, and ORR have been shown to improve among patients receiving bevacizumab versus those who are not given this antibody, this trend fails to convincingly reach statistical significance. In addition, one of these studies 25 shows in a univariate analysis that treatment with bevacizumab is an important prognostic factor for improved survival time.…”

“…On scrutiny, only four articles were relevant studies. 2,5,24,25 All four were cohort studies. No randomized controlled trials were available to date.…”

“…24 Duodenal ampullary carcinomas were included as part of SBA. After scrutiny, one of the three retrospective cohort studies 25 was excluded because of the lack of data for the outcomes of interest in this review (no separate data for OS, PFS, and ORR for the subset of patients with SBA who received bevacizumab plus cytotoxic chemotherapy; Figure 1).…”