Selection of Large and Objectively Measurable Target Lesions in Eortc Phase-ii Trials - Impact On Recruitment and Response Rate

The EORTC has recently issued minimum requirements for target lesions in phase II trials, aiming at a decrease in measurement errors [minimum size, computer tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment and response has been retrospectively studied in a trial of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients with advanced soft tissue sarcoma, where 46/103 objective responses were seen, including 10 complete responses. For the 20 patients who did not satisfy the criteria, a similar objective response rate and a significantly higher complete response rate were reported. Among 265 target lesions, the same trends were observed when comparing small to large lesions, for different tumour sites. For deep lesions clinically assessed, significantly higher response rates were reported than for those measured by CT scans or ultrasound. The new stricter EORTC criteria improve the reliability of measurements and have been adopted for future phase II trials of the STBSG. This will not result in the selection of potentially poor responders. Less than 20% of the present recruitment will be lost

PHASE-II CLINICAL-TRIAL OF DOXIFLURIDINE IN PATIENTS WITH ADVANCED OVARIAN-CANCER

35 evaluable patients were treated with 5'-deoxy-5-fluorouridine (doxifluridine), a fluoropyrimidine derivative. All patients had been heavily pretreated and had refractory disease. Treatment with doxifluridine at a dosage of 3000 mg/m2 given intravenously for 5 successive days at 3-week intervals led to 6 partial remissions (17%). The main side-effects were central neurotoxicity, stomatitis and myelotoxicity, resulting in 2 toxic deaths. In patients with renal function disturbances, toxicity proved to be more severe. We concluded that the drug should not be used in patients with renal impairment. Because responses have been encountered, further evaluation of the drug may be warranted in the less toxic oral form

An EORTC phase II study of the efficacy and safety of linomide in the treatment of advanced renal cell carcinoma

The aim of this study was to determine the objective tumour response rate and duration of response and toxicity of linomide (Roquinimex) treatment in patients with disseminated renal cell carcinoma, pretreated or not pretreated with immunotherapy, From March 1991 to July 1992, 72 patients with metastatic and progressive renal cell cancer were entered of whom 9 (12%) were not evaluable for response. Linomide was given orally, twice weekly, 5 mg during the first week with dose escalation to 10 mg during the second week and 15 mg thereafter. Treatment was continued until disease progression or unacceptable toxicity. No haematological toxicity but slight anaemia was observed. A significant WBC (white blood cell count) increase (P < 0.0001, paired T-test) was found during treatment. The most often reported non-haematological side-effects were: flu-like syndrome (54%, grade III-IV 7%), nausea/vomiting (41% and 3%, respectively) and neurotoxicity (34% and 2%). Most side-effects were of mild or moderate intensity (WHO grade 1 or 2). The objective overall response rate was 4%: 1 CR and 2 PRs. Stable disease was reported for 28 patients (40%). The duration of response was 17, 22 and 30 (CR) months. Median time to progression was 5 months. Linomide at the given dose and schedule is well tolerated, but has limited antitumour activity in metastatic renal cell carcinoma. (C) 1997 Elsevier Science Ltd