Malignant Neoplasms of the Small Intestine Treatment & Management

Updated: Dec 31, 2015
  • Author: Ponnandai S Somasundar, MD, MPH, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment

Medical Care

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  • Because of its low prevalence, few clinical trials have been performed to assess the efficacy of chemotherapy for treating small-bowel cancer.
    • The largest published study was in 1984 by Jigyasu et al and involved 14 subjects with metastatic small-bowel adenocarcinoma who were treated with 21 chemotherapy regimens, most containing 5-fluorouracil (5-FU). Two minor responses and one partial response occurred, with a median survival of 9 months. [25]
    • In their 1984 review of 65 patients with small-bowel adenocarcinoma, Ouriel and Adams reported a mean survival of 10.7 months in 6 patients with metastatic disease treated with 5-FU–based regimens, compared with a mean survival of 4 months in 6 patients with metastatic disease who received no chemotherapy. An additional 6 patients with recurrent disease were also treated with chemotherapy and had a mean survival of 11.5 months, compared with 21 patients with recurrent disease who received no chemotherapy and survived a mean of 7.9 months. [26]
    • More recently, a 1998 British study by Crawley et al reported 8 patients with advanced small-bowel adenocarcinoma treated with infusional 5-FU–based regimens and found a response rate of 37.5% and a median survival of 13 months. [27]
    • A Japanese study by Nakanoko et al concluded that curative rsection and definitive chemotherapy for unresectable cases can be an effective treatment approach. [28]
  • Newer agents found to be effective for colorectal carcinoma also may be active for small-bowel adenocarcinoma.
    • As reported by Polyzos and colleagues in 2003, 3 subjects with 5-FU–refractory small-bowel adenocarcinoma were treated with salvage irinotecan therapy. Two patients achieved a minor response and had improvement of their symptoms. [29]
    • Also in 2003, Bettini and colleagues found that the FOLFOX 4 regimen (ie, combination infusional 5-FU, oxaliplatin, and leucovorin) was safely administered as adjuvant chemotherapy in 3 patients with resected small-bowel adenocarcinoma associated with celiac disease. [30]
  • Because these are uncontrolled studies with few patients, drawing conclusions regarding the benefit of chemotherapy for small-bowel adenocarcinoma, either in the metastatic or adjuvant setting, is difficult. In patients with a good performance status, any attempts using the regimens mentioned seem reasonable. [31]
  • Similarly, few studies have assessed the efficacy of cytotoxic chemotherapy for small-bowel sarcomas. An analysis by Fernandez-Trigo and Sugerbaker from 1993 reported on 7 randomized prospective studies of subjects with nonextremity sarcomas and found no survival benefit with the addition of adjuvant chemotherapy after surgery. [32]
  • Studies of chemotherapy in patients with metastatic GI soft tissue sarcomas have also yielded disappointing results.
    • For example, the Southwest Oncology Group, as reported by Zalupski et al in 1991, found that only 3 (7%) of 43 subjects with GI sarcomas responded to a combination of doxorubicin and dacarbazine, whereas 21% of subjects with leiomyosarcomas of other sites responded to the same combination. [33]
    • A trial reported by Blair et al in 1994 found that a combination of ifosfamide and etoposide produced no responses among 10 patients with GI sarcomas. [34]
  • Evidence indicates that in general, small-bowel sarcomas and GISTs are more resistant to chemotherapy than sarcomas in other sites. A 2000 Dutch study by Plaat et al found greater expression of multidrug-resistance proteins in GISTs compared with non-GI leiomyosarcomas. [35]
  • Unlike conventional chemotherapy, the recently developed novel agent imatinib mesylate (also known as STI571 and Gleevec) has shown promising activity in GISTs. Imatinib is a small molecule that selectively inhibits the tyrosine kinase activity of bcr-abl, c- kit, and PDGFR.
    • In 2002, Demetri et al reported a multinational study of 147 subjects with advanced GISTs who were randomized to receive 400 mg or 600 mg of imatinib daily. Results demonstrated a 54% partial response rate and 28% stable disease, with a median duration of response greater than 24 weeks and no differences in response between the two doses. [36]
    • Another study of imatinib by the European Organization for Research and Treatment of Cancer, as reported by van Oosterom et al in 2002, indicated a 54% partial response rate and 37% stable disease rate, with a duration of response greater than 10 months, among 35 subjects with GISTs. [37]
  • These studies have led to the US Food and Drug Administration approval of imatinib for advanced GISTs. However, its effect on survival and its role in the adjuvant setting remain to be defined by the results of ongoing randomized clinical trials.
  • The FDA has recently approved Sunitinib (Sutent) as targeted therapy for patients in whom imatinib fails in the form of disease progression or inability to tolerate the drug.
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Surgical Care

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  • Surgical resection provides the only hope of cure for patients with small-bowel adenocarcinomas. This is possible in approximately two thirds of patients. The remaining have unresectable disease as a result of extensive local disease or metastases to regional lymph nodes, the liver, or the peritoneum.
  • Use wide local excision on lesions in the distal duodenum, jejunum, or ileum.
    • Patients with lesions in the proximal duodenum, including those in the periampullary region, should undergo pancreaticoduodenectomy, which now has an operative mortality rate of less than 5%.
    • Several studies have shown that patients who undergo resection have an improved 5-year survival rate of 40-60%.
    • Surgery is indicated for palliation in patients with symptomatic advanced disease, such as intestinal obstruction.
    • Ileal tumors are more likely to develop intestinal obstruction than jejunal tumors. Emergency surgery for these patients relieves the obstruction but precludes a complete and negative margin resection.
  • Despite the efficacy of imatinib for GISTs, surgical resection remains the primary therapy for small-bowel sarcomas, although 35-50% are unresectable because of metastatic disease. Similar to proximal duodenal adenocarcinomas, small-bowel sarcomas located in this region should be resected with a pancreaticoduodenectomy.
    • Those in the distal duodenum, jejunum, or ileum should be resected with wide margins; tumors close to the ileocecal valve may require a right hemicolectomy. DeMatteo et al reported a series from Memorial Sloan-Kettering of 200 patients with GISTs showing median survival of patients with complete excision was 66 months, as opposed to those with incomplete resection at 22 months, justifying the removal of adjacent organs to obtain complete resection of the primary disease. [9]
    • Lymph node metastasis is rare, and therefore an extensive lymph node dissection is not recommended.
    • Resection appears to prolong survival, but recurrence with widely metastatic disease is typical.
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Consultations

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  • Gastroenterologist: This specialist may assist in diagnosis through upper GI endoscopy and colonoscopy.
  • Radiation oncologist
    • Although no survival benefit is achieved with adjuvant radiotherapy after surgery for small-bowel adenocarcinoma or sarcoma, radiotherapy may be useful as a palliative procedure for pain relief or obstructive symptoms in patients with advanced disease. Also, radiotherapy may be of benefit for controlling chronic tumor-related blood loss.
    • While postoperative radiotherapy has been shown to improve local control for sarcomas of the extremities, its role for GIST and GI sarcomas is not clear. Adjuvant brachytherapy and intraoperative radiation are also being investigated for treatment of GI sarcomas.
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