Protracted venous infusion 5-fluorouracil and interferon-α in advanced and refractory colorectal cancer

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Abstract
The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-α, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU. Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-α was added and further outcome evaluated. One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/ 69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-a added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-a addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-a gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months. Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-a at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-α can be recommended as a modulator of 5-FU in the clinical setting.

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