Phase II study of doxifluridine in advanced colorectal adenocarcinoma.

Abstract

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.

Prospective Multicenter Phase-Ill Trial of Doxifluridine (5’dFUR) versus 5-Fluorouracil in Patients with Advanced Colorectal Carcinoma

“…Our results are similar to the reported trials in the treatment of advanced colorectal carcinoma [8,9,13,15]. There is no advantage for response dependent on routes of administra tion, but the one hour infusion showed low toxicities in contrast to the bolus injection and 6-hours infusion.…”

“…In several contributions [8,9,13,15] as well as in our own previous experiences [14] it was clearly outlined that 5'dFUR is active for treatment of colorectal carcinoma. However, the optimal dose and route of application is still controversial.…”

“…Cytotoxic activity varies considerably, the highest occurring in tumor tissue and small intestine [5], In a phase-I clinical trial using a daily schedule with rapid intravenous injections for five consecutive days, doses were escalated up to 5 g/m2. Granulocytopenia as well as stomatites were found to be dose limiting, and other toxic effects con sisted of nausea/vomiting, central nervous system symptoms and ECG changes [6], Disease-oriented phase-II trials have demonstrated cytotoxic activity of 5'dFUR in a variety of solid tumors including ovarian carcinoma [7], colorectal carcinoma [8,9], malignant melanoma [10], head and neck [11] as well as breast carcinoma [12] if the drug was administered at a daily x 5 schedule for one hour infusion or for bolus injection. The dose limiting toxicities encountered in these trials were leukopenia, stomati tis and cerebellar ataxia.…”

Cardiac Toxicity with Capecitabine, Vinorelbine and Trastuzumab Therapy: Case Report and Review of Fluoropyrimidine-Related Cardiotoxicity

“…The cardiotoxic effects of 5-FU have been extensively reported [3,4,5,6,7,8,9]. More recently, cardiotoxicity has been reported with doxifluridine [10], tegafur [11] and the oral fluoropyrimidines capecitabine [12,13,14,15,16] and UFT [17,18,19], predominantly in patients with colorectal cancer. We report a case of cardiotoxicity during the first cycle of capecitabine treatment in a woman with metastatic breast cancer, followed by a review of the available literature and a discussion of the possible pathophysiology of this cardiotoxicity and its implications for practice.…”

Dose–Finding Study of 5&#8217;-Deoxy-5-Fluorouridine in Combination with Fixed Doses of Cisplatin and <i>L</i>-Folinic Acid for the Treatment of Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

“…x 5 days in good-or poor-risk patients, respectively, demonstrated that 5dFUR has def inite activity in a variety of tumors usually sensitive to fluoropyrimidines, such as carcinoma of the breast [20], colon-rectum [21 ], and of the head and neck district [22], Furthermore, some comparative trials with 5FU for 5 consecutive days were carried out in colorectal cancer [23,24], Also in these trials, the infusion time seemed to affect both type and severity of toxicity. Indeed, a higher occur rence of neurologic (48%) and cardiac toxicity (19%) as compared to the parent compound was reported when 5dFUR was administered as intravenous bolus [23], while these side effects affected 23 and 1% of patients, respec tively, when 5dFUR was given as 1-hour intravenous infusion [24], In advanced SCCHN, the combination of CDDP and continuous intravenous infusion 5FU, with or without the addition of L-FA, has demonstrated to be a very active treatment itself, for unresectable or recurrent disease [4][5][6][7][8].…”