Clinical and pharmacological studies of interferon and chemotherapy in gastrointestinal and breast cancer.

The interferons enhance the cytotoxicity of antimetabolites, alkylating agents, and plant antibiotics against cultured human tumours in vitro and in vivo. Five clinical trials in humans with advanced colorectal carcinoma have demonstrated responses ranging from 26 to 63% in patients treated with 5-fluorouracil (5-FU) plus interferon-alpha (IFN-alpha), suggesting improved response with the combination as compared with 5-FU alone. In addition, responses have been observed in patients with adenocarcinomas of the lung, pancreas, breast, and kidney, squamous cell carcinoma of the oesophagus, and urothelial carcinoma treated with 5-FU/IFN-alpha. However, enhanced 5-FU-related toxicity was observed in these studies, as has been observed when 5-FU is combined with other modulating agents, such as leucovorin. While some studies suggested that enhanced 5-FU-related toxicity was associated with an IFN-alpha-induced reduction in 5-FU clearance when 5-FU was given as an intravenous (i.v.) bolus (750 mg/m2 IV weekly) or as a high-dose five-day continuous infusion (CI) (750 mg/m2/day x 5 days), another study found enhanced 5-FU toxicity in the absence of pharmacokinetic perturbation when 5-FU was given as a low-dose prolonged CI (300 mg/m2/day x 28 or more days).(ABSTRACT TRUNCATED AT 250 WORDS)