The Royal Marsden experience of small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil

Abstract

Summary The purpose of this study was to review the efficacy of a protracted venous infusion of 5-fluorouracil (PVI 5-FU)-based chemotherapy in advanced small bowel adenocarcinoma. Data on all patients with small bowel malignancy who were seen at a single institution over a 5-year period were retrieved from the gastrointestinal unit and hospital databases, and these cases were reviewed. Eight patients with advanced small bowel adenocarcinoma received PVI 5FU-based chemotherapy. The overall response rate in assessable patients was 37.5% (3/8). The median overall survival was 13 months (range 1-28), and progression-free survival was 7.8 months (range 0-15). Overall, the treatment was well tolerated and symptomatic benefit was seen. In conclusion, PVI 5-FU has activity in this disease. This should be assessed either as a single agent or as part of a combination regimen such as epirubicin/cisplatin/PVI FU (ECF) in a multicentre randomized study.Keywords: small intestine; adenocarcinoma; 5-fluorouracil; infusional treatment Although adenocarcinoma is the most common small bowel tumour, it still represents less than 1% of gastrointestinal (GI) tract tumours. The standard treatment is surgery with a resection rate of 35-77%. The operative mortality of surgery with a curative intent is 0-18% and the 5-year survival is 10-62% (Delcore et al, 1993;Ouriel and Adams, 1984). The role of radiotherapy and chemotherapy is less clear. There are reports of prolonged survival with combination chemo-and radiotherapy following palliative bypass surgery or incomplete resection and reports suggesting a better prognosis compared with pancreatic carcinoma (Sakker and Ware, 1973;Yeung et al, 1993). Data on the use of chemotherapy alone are limited. Regimens used have been very varied, and some series have been collected over prolonged periods (Sakker and Ware, 1973;Okhusa et al, 1991). METHODSThe GI unit and hospital databases were searched for patients referred to the Royal Marsden Hospital (RMH) with malignancy of the small bowel during the period 1990-95. Pathology was reviewed at RMH before treatment. Data regarding diagnosis, treatment, toxicity and response were collected prospectively. Responses were assessed according to the WHO criteria (Miller et al, 1981). Symptomatic responses were recorded prospectively on the GI database; improvement was defined as disappearance of a symptom for >3 weeks.

Multicenter Retrospective Study of 132 Patients with Unresectable Small Bowel Adenocarcinoma Treated with Chemotherapy

“…Fluoropyrimidines are generally considered to be the key drugs for SBA and other gastrointestinal cancers. Most regimens used in previously reported studies of chemotherapy for unresectable SBA included fluoropyrimidines; to date, there has been no active regimen without these drugs [11][12][13][14][15][16][17][18][19][20][21][22][23]. However, no prospective or retrospective study has clearly showed advantages of a combination regimen compared with fluoropyrimidine monotherapy for unresectable SBA with regard to PFS or OS times.…”

“…Fluorouracil (5-FU) is the most commonly used agent for the treatment of unresectable or recurrent SBA, and various 5-FU based regimens have been used [11][12][13][14][15][16][17][18][19][20][21][22][23]. In a retrospective analysis, Overman et al reported that combination therapy with 5-FU and platinum compounds showed more favorable results than other regimens [21].…”

Phase II Study of 5-fluorouracil, Doxorubicin, and Mitomycin C for Metastatic Small Bowel Adenocarcinoma

“…Although most experience is with colorectal, gastric, and esophageal cancers, additional reports of treatments for advanced small bowel adenocarcinoma do exist. Crowley et al [11] reported the Royal Marsden experience of using infusional 5-FU as a single agent or in combination with cisplatin and epirubicin (Ellence ® ; Pharmacia and Upjohn; Portage, MI), the ECF regimen [10]. Of the eight patients assessable for response, one achieved a CR and two achieved PRs (RR = 37%), with a median overall survival time of 13 months.…”

Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

“…Risk factors for SBA, including Crohn’s disease, celiac sprue, familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer syndrome, Peutz-Jeghers syndrome, and type 1 neurofibromatosis, account for a minority of cases [2]. This mostly sporadic pattern of occurrence, along with the lack of specificity of clinical symptoms, largely explain why approximately one half of cases of SBA are not diagnosed prior to surgery, and why up to two thirds of cases are not amenable to curative resection at the time of diagnosis [1,3,4,5]. Patients with high-stage tumors remain at risk of recurrence even after complete resection [6], and the benefit of adjuvant therapy in such patients is still debated [6, 7].…”