Phase II study of 5-fluorouracil, doxorubicin, and mitomycin C for metastatic small bowel adenocarcinoma.
BACKGROUND
Small bowel adenocarcinoma is a rare gastrointestinal malignancy that is treated primarily with surgery. Even with optimal resection, however, survival is poor and recurrences are common. Response rates to palliative combination chemotherapy are low, and the median duration of survival for metastatic disease is less than 1 year. This study aimed to document the response rate and survival time for patients with advanced small bowel adenocarcinoma who were not surgically curable and were treated with a regimen of 5-fluorouracil (5-FU), mitomycin C (Mutamycin; Bristol-Myers Squibb; Princeton, NJ), and doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH), the FAM regimen.


METHODS
This multi-institutional study was performed by the Eastern Cooperative Oncology Group (ECOG). Between November, 1983 and December, 1985, 39 patients with advanced or recurrent disease were enrolled. Chemotherapy was given as follows: 5-FU, 600 mg/m(2) on days 1, 8, 29 and 36; mitomycin C, 10 mg/m(2) on day 1; and doxorubicin, 30 mg/m(2) on days 1 and 29. Eligibility criteria included an ECOG performance status score of 0-2, measurable disease, and adequate baseline organ function. Prior chemotherapy was allowed. Response was measured by examination and imaging techniques. Survival time and time to progression were evaluated by the method of Kaplan and Meier, and these outcomes were stratified by clinical and laboratory covariates.


RESULTS
Of the 39 evaluated patients, 38 were eligible and 36 were evaluable for response. Grade 3-5 toxicities were experienced by a total of 26 patients (20 grade 3, 5 grade 4, 1 grade 5). The most common adverse events were neutropenia and vomiting. Responses were seen in a total of seven patients (2 complete responses, 5 partial responses), for a response rate of 18.4% (95% confidence interval of 7.8%-34.4%). The median survival time was 8 months.


CONCLUSIONS
The FAM regimen was active and tolerable for patients with advanced small bowel adenocarcinoma; however, the results were no better than those seen with other chemotherapy combinations.