A. Tres

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).

75 A pilot study of adjuvant postoperative chemohormonal therapy with 5-fluorouracil, doxorubicin, cyclophosphamide, vindesine and tamoxifen for resectable breast cancer

Adjuvant systemic therapies have proved effective to increase diseasefree survival (DFS) and total survival at 5 and 10 years in patients with “resectable” breast cancer. However, the amount of the benefit is at best moderate. There is a need of more effective regimens. We show the results of a pilot trial of postoperative adjuvant therapy with 6 cycles of 5-Fluorouracil 600xa0mg/m 2 , doxorubicin 50xa0mg/m 2 , cyclophosphamide 600 mg/m 2 and vindesine 3xa0mg/m 2 (maximum 5xa0mg), all endovenous on day 1, repeated every 28 days, plus Tamoxifen (20xa0mg/day) continued for 2 years (not in ER negative tumors). This schedule of chemohormonotherapy had been demonstrated highly active in metastatic breast cancer. Three-hundred and five patients (pts) have been treated. Menopausal status was: premenopausal in 93 pts and postmenopausal in 212. ER status was (+) in 90 pts, (−) in 61 pts and unknown in 154 pts. Twenty-three pts had node negative stage II tumors with peripheral blood or lymph vessel invasion (PBLI), 75 pts had 1 to 3 positive nodes, 33 pts had 4 to 10 positive nodes, 15 pts had 10 or more positive nodes and 159 pts had technically respectable stage III tumorsxa0+/−xa0axillary nodes (N0, N1 o N2). (stage IIIA 87 pts and stage IIIB 72 pts). More than 90% of the patients received 6 cycles of chemotherapy at full dose. Median follow-up is now 44 months (80 pts followed for 5 years or longer). Actuarial 5 year DFS is 84% for N(–) stage II with PBLI; 79% for pts with stage II (1–3 nodes); 70% for pts stage II (3–10 nodes); 62% for stage II (>10 nodes) and 56% for stage III. DFS and total survival according to menopausal status and ER status will be presented. We feel that such stimulating results in this uncontrolled pilot trial deserve testing in a randomized multi-institutional study.