Randomized, controlled study of continuous 5-FU infusion starting immediately after curative surgery for advanced colorectal cancer. Controlled evaluation of three drug combination regimens versus fluorouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group. 5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study. Multimodal analgesia before thoracic surgery does not reduce postoperative pain. Randomised clinical trial of adjuvant postoperative RT vs. sequential postoperative RT plus 5-FU and levamisole in patients with stage II-III resectable rectal cancer: a final report. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study. [A double-blind randomized comparative study of oral 5-fluorouracil (5-FU), cyclophosphamide (CPA), and 5-FU + CPA in advanced breast cancer].
The usefulness of adjuvant chemotherapy started immediately following surgery was evaluated.
                A randomized clinical trial was performed on 133 patients with advanced colorectal cancer using oral anticancer agents with one-week continuous 5-FU infusion starting immediately after curative surgery. In Group A and Group B, 300 mg/day of HCFU was orally administered for two years starting two weeks after surgery, and in addition, 333 mg/m2/day of 5-FU was drip infused from the central vein for seven days from the day of surgery in Group B.
                For 1919 days after surgery, there were no significant intergroup differences in overall survival (OS) and disease-free survival (DFS), but OS and DFS in Group B rectal cancer patients were significantly better when compared to Group A rectal cancer patients. On the other hand, OS tended to be better in Group A colon cancer patients, but no significant intergroup differences were seen, while intergroup differences tended to be smaller when corrected for disease stage.
                Continuous 5-FU infusion starting immediately after curative surgery for colorectal cancer was safe. While further investigation is necessary to elucidate the degree of improvement in postoperative prognosis, the results of the present study suggest that continuous 5-FU infusion improves prognosis in advanced rectal cancer. The purpose of this study was to evaluate the therapeutic effectiveness of fluorouracil (5-FU), doxorubicin, and methyl lomustine (CCNU) (FAMe), 5-FU, doxorubicin, and cisplatin (FAP), and FAMe alternating with triazinate (TZT) when compared with a standard therapy of 5-FU alone in patients with advanced gastric cancer.
                Two hundred fifty-two eligible patients selected for study had proven locally unresectable and/or metastatic gastric adenocarcinoma. The majority had nonmeasureable disease. They were randomly assigned to receive one of the three drug combination regimens or to 5-FU alone administered by rapid injection in 5-day course. Survival was the primary study end point.
                None of the three drug combinations showed a significant advantage over 5-FU alone in improved performance score, weight gain, or patient survival. Each of the three combinations was more toxic than 5-FU alone.
                FAMe, FAP, or FAMe alternating with TZT cannot be recommended for the therapy of advanced gastric carcinoma. Therapy of this disease should remain an experimental endeavor. It would seem reasonable to prove the value of any new treatment approach by a randomized comparison to simple therapy with 5-FU alone. Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy.
                Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections.
                Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02).
                Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy. Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain. A randomised clinical trial was performed in patients undergoing radical surgery for rectal cancer to compare the efficacy and toxicity of adjuvant postoperative radiation therapy (RT) to sequential RT and chemotherapy (CT) with 5-fluorouracil (5-FU) plus levamisole (LEV). The primary end point was overall survival (OS); secondary end points were disease-free survival (DFS), the rate of loco-regional recurrence, and treatment-related toxicity; the final results of this trial are reported.
                Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/sqm/day intravenous (i.v.) bolus, days 1-5) plus LEV (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and LEV every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were in the normal range.
                From May 1992 to December 1998, 218 patients were enrolled into the randomised clinical trial (144 men, 74 women; age range: 28-75, median 64 years). The median follow-up time was 58.1 months (range: 1-3,271 days). No significant difference was observed between the two arms of treatment as regards OS and DFS (P = 0.18 and P = 0.66, respectively). Cox regression analysis for OS confirmed what was observed by univariate analysis for all variables except age. Older age (>60 years) and pathologic lymph-node involvement defined the subgroups with the worst prognosis. Cox regression analysis for DFS confirmed what was observed by univariate analysis for all variables: the only independent variable in predicting DFS was pathologic lymph-node involvement.
                Our findings suggest no difference in OS, loco-regional and distant site progressions of postoperative RT alone compared to sequential postoperative RT and CT; notably, this latter regimen was associated with higher toxicity which seriously impaired the patient's compliance to CT. The low loco-regional recurrence rate (9.2%) observed in our patients undergoing postoperative RT alone compared to similarly treated patients in previously performed clinical trials (20-25%) underline the role of radical surgery (mesorectal excision) coupled with a complete postoperative RT regimen. On the other hand, the similar efficacy of these two adjuvant modalities of treatment might be conditioned by both the low compliance (59%) to the CT regimen as well as the sequential, instead of concurrent, schedule of administration of RT and CT, which may have decreased further the expected efficacy of the combined regimen.
                Copyright 2003 Wiley-Liss, Inc. To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx.
                Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis.
                From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10).
                Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT. A randomized trial was performed comparing the effects of oral 5-fluorouracil (5-FU), 300 mg/day, cyclophosphamide (CPA), 150 mg/day and 5-FU + CPA in advanced breast cancer. Some 181 patients were entered in the trial, with 1 ineligible, and 14 incomplete cases. Then 166 were evaluated for their rates of response in the treatment groups: 14.0% (8/57) in 5-FU, 23.6% (13/55) in CPA, and 37.0% (20/54) in 5-FU + CPA, with a P value of 0.019. The difference in response rates between 5-FU and 5-FU + CPA was shown to be significant (p = 0.005). When long NC was included in the comparison, there was a significant difference (p = 0.006) between the groups. A higher incidence of adverse effects was noted in the combination group. A significant difference was noted in TTP (time to progression) among the 3 groups (p = 0.0144), and between 5-FU and 5-FU + CPA (p = 0.0061). There were no significant differences in the overall survival among the groups (p = 0.6808). In conclusion, the combination oral treatment of 5-FU and CPA appears effective as a first line therapy for advanced breast cancer, and also in the postoperative adjuvant setting.
Postoperative injections of 5-FU are now rarely used as a planned series but are increasingly used on an ad hoc basis. This presumably reflects an aspect of the treatment that is unacceptable to both patients and doctors. None of the trials reported on the participants' perspective of care which constitutes a serious omission for an invasive treatment such as this.