Search

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS).Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes.Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival.Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative with a better therapeutic index than FU (Bajetta, Eur J Cancer, 1993). This study independently evaluated the activity of two different schedules of oral or i.v. 5-dFUR plus levo-Ieucovorin. Between April 1993 and September 1994, a total of 130 untreated (in an adjuvant and metastatic setting) pts with measurable colorectal cancer were randomized to 5-dFUR 750mg/m2p.o. on days 1→4 and levo-leucovorin 25mg/dose p.o. two hours before 5-dFUR, repeated every 12 days (Arm A); or 5-dFUR 3000mg/m2as a one hour i.v. infusion for 5 consecutive days combined with levo-leucovorin 25mg/dose i.v. immediately before 5-dFUR every 21 days (Arm B). The first response evaluation was made after 2 mos of treatment. The two arms were well balanced in terms ofage (median 61 yrs, range 31–80), sex (M/F: 69/61) and disease extension. A preliminary intent-to-treat analysis was made of 126 adequately treated pts (4 too early to evaluate), of whom 67 were in Arm A and 59 in Arm B. The response rates were 15% in Arm A (2 CR, 8 PR, 29 SD, 28 PD) and 39% in Arm B (5 CR, 15 PR, 15 SD, 21 PD). Toxicity included WHO grade 3 and 4 diarrhea in respectively 16% and 7% of Arm A and 16% and 15% of Arm B respectively. Mucositis was mainly observed in Arm B (grade 3 in 13% and grade 4 in 1%). The preliminary data confirm the good tolerability profile of both the oral and the i.v. schedule. The oral route seems to be promising and is interesting, because it could be benefit for pts suitable for home treatment. Moreover, this study confirms the efficacy of i.v. doxifluridine as a fast line therapy in advanced colorectal cancer. Data management by I.T.M.O. (ltalian Trials in Medical Oncology) Scietific Service.

PurposeThis phase II study was undertaken to define the toxicity and therapeutical activity of a Fotemustine-DTIC-IFN combination in patients (pts) with metastatic melanoma.

In a preliminary study we demonstrated that the dosage of MTX required to achieve a MTX serum level above 1μM for at least 24h was 500mg/sqm i.v. A combination of MTX 500mg/sqm i.v.(day 1), LFA 250mg/sqm i. v. +5FU 600mg/sqm i. v. (day 2) every 2 wks in the treatment of 94 consecutive pts with advanced gastrointestinal malignancies was demonstrated as effective as other biochemical modulation of 5FU. In addition, a MTX serum level ≥2μM seemed related to the probability of response. From Sept. 1994 to date, 48 pts affected by advanced carcinoma of the digestive tract were treated every 2 weeks for at least 4 courses with MTX 750mg/sqm on d. 1, LFA 250mg/sqm + 5FU 800 mg/sqm on d.2. Presently, 29 pts are evaluable for response. Primary site was large bowel in 22, stomach in 4, gall-bladder in 2, and pancreas in 1. Fourteen pts had received a previous systemic chemotherapy, mainly with fluoropyrimidine ± LFA. We obtained 1 CR and 5 PRs (OR 21%). Chemotherapy-naive pts showed an OR in 33% of cases (stomach 33%, colon-rectum 40%), while responses were reported in 7% of previously treated pts. The most common acute toxicities were mucositis (WHO G 3–4 in 6% of courses and 19% of pts), and leucopenia (5% and 15%).