Randomized Phase II Study of a Combination of Cisplatin (DDP), 5-Fluorouracil (5-FU), and Allopurinol (HPP) Versus 5-FU in Advanced Colorectal Carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group Study

Abstract

In order to improve the therapeutic index of fluorouracil (5-FU), it has been combined with cisplatin (DDP) as synergistic agent and with allopurinol (HPP) as toxicity modulator. Patients with measurable colorectal carcinoma, previously untreated by chemotherapy, were randomized to receive either 5-FU alone 500 mg/m² push iv days 1–5 or HPP 3 300 mg po, days 1–5, 5-FU 800 mg/m² push iv, days 3–5 and DDP 50 mg/m² d6. Treatment was repeated every 4 weeks. Of 104 patients randomized, 82 were evaluable for response and survival. Six partial responses were seen in each treatment group (15%) and the median survival time was 7 months. Hematologic toxicities were comparable in both treatment groups, with a mean nadir white blood cell count of 3500/ vs. 3800/mm³ and a mean nadir platelet count of 148,000/ vs. 203,000/mm³ for HPP-5-FU-DDP and 5-FU, respectively. This study suggests that the addition of both HPP and DDP does not improve the activity of 5-FU.