Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer.

The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m(2)/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m(2)) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m(2)) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m(2)) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4-6.6 months) and median survival was 11 months (95% CI: 7.9-14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m(2) i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m(2) p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m(2) and UFT 300 mg/m(2).

Phase II trial of oral tegafur and folinic acid with mitoxantrone as first-line regimen in patients with metastatic breast cancer.

BACKGROUND: Tegafur acts as a deport form of 5-fluorouracil when administered orally for long periods of time since it is an active drug in metastatic breast cancer, with response rates of 29-44%. Biochemical modulation with folinic acid and the addition of mitoxantrone could increase the efficacy of tegafur in patients with metastatic breast cancer. METHODS: A prospective phase II trial in patients with previously untreated metastatic breast cancer was carried out. The scheme consisted of mitoxantrone, 12 mg/m2 intravenous day 1, oral tegafur, 750 mg/m2/day divided in three equal doses, and leucovorin 15 mg/8 h orally for days 1-21, given in a 4-week schedule. None patient had received chemotherapy for metastatic breast cancer, although 16 patients had received previous adjuvant chemotherapy. RESULTS: Thirty-four patients were included. Objective responses were achieved in 20 of 32 patients assessable for response, with 1 complete response and 19 partial responses. The objective response rate was 62.5% (95% confidence intervals, 48-76%). The median duration of response was 10 months. Grade III-IV toxicity according to WHO criteria was digestive (nausea/vomiting) in 12.5%, diarrhea in 25% and stomatitis in 25% of patients. Other toxicities were low. Eight patients required dose-reduction. CONCLUSIONS: We achieved a significant response rate with the scheme, which was administered on an outpatient basis. It seems to be safe and effective as first-line treatment in metastatic breast cancer, with a short median response duration. The size of the trial does not permit definitive conclusions, and the role of biochemical modulation of tegafur in combination with mitoxantrone remains to be defined.

[Combined concomitant chemotherapy and radiotherapy with or without surgery in the treatment of non-metastatic squamous carcinoma of the esophagus]. / Combinación de quimioterapia y radioterapia concomitantes con o sin cirugía en el tratamiento del carcinoma escamoso de esófago no metastásico.

Between June 1986 and October 1992 two prospective non-randomized and consecutive therapeutic schemes with a curative intent of non-metastatic squamous cell carcinoma of the esophagus were developed. The first scheme consisted of concomitant administration of chemotherapy (cisplatin and 5-fluorouracil, 2 cycles) and radiotherapy (30 Gys) after surgery (esophagectomy) (14 evaluable patients). Without surgery, a higher dose of chemotherapy (4 cycles) and radiotherapy (55 Gys) was given on the second scheme (12 evaluable patients). Complete histological response was 42.6% for the first scheme and 50% for the second one. Toxicity was moderate in both schemes. Palliation was important in the second scheme. Actuarial survival was 28% at 1 year for the first scheme and 71% for the second one. Operative mortality was 27%. Concomitant chemoradiotherapy might be a therapeutic choice for locoregional control of squamous esophageal carcinoma.

[Wilm's tumor in adults. Review of the literature on prognostic factors and treatment]. / Tumor de Wilms del adulto. Revisión de la literatura sobre factores pronósticos y tratamiento.

The incidence of adult Wilms' tumor is difficult to determine but the lesion is rare. The prognosis is poorer than in children, but in adults is often diagnosed at a higher clinical stage and with an unfavorable histologic type. There may be other reasons for the poor prognosis as well. A 33-year-old woman with metastatic disease (bilateral kidney tumors, pulmonary and multiples lymph nodes metastases) is described. Treatment with chemotherapy consisted of doxorubicin, ifosfamide and etoposide which resulted in complete remission that persisted for only three months. The factors that probably contributed to rapid progression included un favorable histology (predominant nodular blastematous elements which were anaplastic) and advanced disease. The precise histologic diagnosis was late precluding to plan the correct treatment.

Combination chemotherapy with docetaxel plus vinorelbine in metastatic breast cancer patients with prior exposure to anthracyclines.

PURPOSE: To evaluate the anti-tumor activity and tolerance of docetaxel plus vinorelbine in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Fifty patients with MBC were treated with docetaxel 75 mg/m2 (subsequently reduced to 60 mg/m2) plus vinorelbine 30 mg/m2 (subsequently reduced to 24 mg/m2). both on day 1, every 3 weeks, for a maximum of six cycles. All patients had previously received anthracyclines as adjuvant treatment (< 12 months disease-free interval) or first-line therapy for MBC. Thirty-seven patients had received at least one prior regimen for MBC. Twenty-five patients had prior high-dose chemotherapy with stem-cell rescue. Thirty patients had multiple metastatic sites. Liver and lung disease were the predominant metastatic site in 31 patients. RESULTS: Forty-nine patients were assessable for response. Nineteen patients achieved a partial response and four a complete response (overall response rate, 46%; 95% confidence interval (95% CI): 32%-60%). Fourteen patients (28%) had stable disease on treatment. Median Kaplan-Meier estimated progression-free and duration of response times are 21 and 29 weeks. Median survival time is 47 weeks. Hematological dose-limiting toxicity, prompted a 20% dose reduction for both drugs after the first thirteen patients were treated. Neutropenia > or = grade 3 occurred in nineteen (34%) patients, neutropenic fever in 15 (7) courses, and mucositis > or = grade 3 in 6 (3%) courses. CONCLUSIONS: The combination of docetaxel plus vinorelbine on day 1 every 3 weeks is feasible and active in MBC patients with prior anthracycline exposure. This regimen is safe, well-tolerated and convenient for the patients.