Phase II trials with flavone acetic acid (NCS. 347512, LM975) in patients with advanced carcinoma of the breast, colon, head and neck and melanoma

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Abstract
Phase II trials of flavone acetic acid have been performed in a total of 87 patients including 17 with advanced breast cancer, 23 with advanced colorectal cancer, 25 with advanced malignant melanoma and 22 with advanced head and neck cancer. Patients with colorectal cancer and melanoma had received no prior chemotherapy; in breast and head and neck cancer patients prior chemotherapy had been given with a median of 5 and 2 drugs respectively. The schedule used was a once-weekly regime, with a dose of 4.8 gms/m2 given as a 1 hour infusion, together with alkalinization (with i.v. sodium bicarbonate) given before and after FAA. Reassessment was performed after 6 weekly doses, although in 23 patients fewer than 6 doses were given, because of early disease progression in 15, and undue toxicity in 5. An additional 3 patients died within 72 hours of having received FAA and, although the precise cause of death in each case was not established, FAA toxicity could not be excluded. Treatment was generally manageable, the major manifestations of toxicity comprising uncomfortable warmth and flushes, nausea, diarrhoea, and visual complaints. Hypotension was also documented in 8 patients. No objective responses were seen in any of the patient sub-groups, although disease-stabilization was seen in 3 patients with breast cancer, 1 patient with advanced colorectal cancer, 2 patients with advanced melanoma and 4 patients with head and neck cancer. Further Phase II studies, using a higher dose of 8.6 gm/m2 over 6 hours once weekly, are currently in progress in Europe. However, Phase II studies to date indicate no antitumor activity of FAA given weekly as a single agent at the maximally tolerated dose over 1 hour.