Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

Adjuvant radiotherapy in resectable pancreatic carcinoma.

AIM: Pancreatic cancer is a near fatal disease. External beam radiotherapy and intraoperative radiation therapy (IORT) has been proposed with the aim to improve clinical outcome in resectable tumors. The aim of this study is to assess the feasibility and outcome in patients with cT1-3 pancreatic cancer, treated with surgery, external beam radiotherapy and IORT. METHODS: From 1990 to 1996, 17 patients with clinical stage T1-3N0-1M0 adenocarcinoma of the head of the pancreas were treated with pancreatectomy and pre- (nine patients: 5 Gy), intra- (all patients: 10 Gy) and post-operative (all patients: 50 Gy) radiotherapy. The pathologic T stages were: 4 pT2 and 13 pT3. The pathologic N stages were: 9 pN0 and 8 pN1. Minimum follow-up in living patients was 60 months. RESULTS: No perioperative mortalities were recorded. Two patients showed postoperative morbidity (11.8%) which required a subsequent laparotomy. The disease-free survival at 1, 3 and 5 years was 41, 23 and 18%, respectively (median: 9 months). The overall survival at 1, 3 and 5 years was 70%, 41% and 18%, respectively (median: 17.5 months). Three patients developed local failure (17.6%) and 12 patients showed distant metastases (70.6%). Univariate analysis (logrank) showed: a significant correlation between both N-stage and retroperitoneal involvement (RPI) with local control (N-stage: P=0.0155; RPI:P =0.0295), a significant correlation between maximum tumor size and metastases-free survival (P=0.0167) and overall survival (P=0.0241); the female gender was another predictor of prolonged survival (P= 0.0465). Multivariate analysis (Cox) showed a significant impact of N-stage and retroperitoneal involvement on local control and also a significant correlation between perineural involvement and tumor diameter with metastases-free survival. CONCLUSIONS: These results are similar to those of other published series and suggest that this approach is feasible with acceptable local control and survival, especially in patients with small tumors (<2.5 cm: 5 year survival=33.3%) and in female patients (5 year survival=30%). Due to the impact of gender, tumor diameter and N stage on prognosis, in the design of future trials a stratification of patients based on these categories should be considered. The search of effective chemotherapeutic agents is required, to reduce the high incidence of distant metastases, especially in larger tumors.

Chemoradiation with or without intraoperative radiation therapy in patients with locally recurrent rectal carcinoma: prognostic factors and long term outcome.

BACKGROUND: Rectal carcinoma patients with local recurrence are reported to have a dismal prognosis. The purpose of this study was to evaluate the effect of combined modality therapy on clinical outcome and to determine the prognostic impact of a "presurgical" staging system. METHODS: Between September 1989 and June 1997, 47 patients (with a median follow-up of 80 months) with locally recurrent, nonmetastatic rectal carcinoma were classified according to the extent of pelvic sidewall involvement as determined by pretreatment computed tomography (CT) scan. They received preoperative external beam radiation (45-47 grays [Gy] in 34 patients; 23.4 Gy in 13 preirradiated patients) plus concomitant 5-fluorouracil (1000 mg/m(2)/day as a 96-hour continuous infusion on Days 1-4 + 29-32) and mitomycin C (10 mg/m(2) as a bolus intravenously on Day 1 + 29). After 4-6 weeks, the patients were evaluated for surgical resection and intraoperative radiation therapy (IORT) procedure (10-15 Gy) or, in unresectable patients, a boost dose was planned by chemoradiation (23.4 Gy) or brachytherapy. Thereafter, adjuvant chemotherapy (5-fluorouracil and leucovorin for a total of six to nine courses) was prescribed. RESULTS: During chemoradiation, 2 patients (4.3%) developed Radiation Therapy Oncology Group Grade 3-4 acute toxicity. Twenty-five patients (53. 2%) had an objective response after chemoradiation. Twenty-one patients (45%) underwent radical surgical resection. The overall 5-year survival and local control rates were 22% and 32%, respectively. The classification system significantly predicted survival (P = 0.008). Radically resected patients had better local control and survival (P < 0.0001); in patients treated with IORT, the 5-year local control and survival rates were 79% and 41%, respectively. CONCLUSIONS: The data from the current study suggest that combined modality therapy was well tolerated and improved resectability, local control, and survival. The classification system appears to be a reliable tool with which to predict clinical outcome in patients with locally recurrent rectal carcinoma.

Organ preservation in rectal cancer.

Treatment of distal rectal cancer is aimed at sphincter preservation. Three trials were conducted to this purpose. They differed for T stage selection and therapy. Two of the trials are now completed, while patients are still recruited for the third trial. 21 T2 patients were selected for the first series and treated with local excision plus postoperative radiotherapy. External beam radiotherapy (ERT) was delivered at the dose of 45 Gy. Grade 3-4 (RTOG) acute toxicity was 5%; late toxicity was never observed. Sphincter function was rated as excellent or good in all patients. Sphincter preservation was achieved in 86% of cases. In the T3 FUMIR trial, 83 patients with extraperitoneal rectal cancer (T3) were treated with concomitant mitomycin C (10 mg/m2, day 1) plus 5FU (1000 mg/m2 days 1-4) plus ERT (38Gy). Grade 3-4 acute toxicity (RTOG) was 13%; late toxicity was never observed. Sphincter function was rated excellent or good in 96% of patients; sphincter preservation was achieved in 66% of patients with a lesion at less than 50 mm from the internal anal orifice. In the T3 PLAFUR trial, 19 patients with extraperitoneal rectal cancer (T3) were treated with concomitant cisplatin (60mg/m2, day 1 and 28) plus 5FU (1000 mg/m2 days 1-4 and 28-32) plus ERT (50.4 Gy). Grade 3-4 (RTOG) acute toxicity was 5%; late toxicity was never observed. Sphincter function was rated excellent or good in 93% of patients. Sphincter preservation was achieved in 73.7% of patients; in particular, in 55.6% of those with a lesion at less than 50 mm from the internal anal orifice. Combined modality therapies are showing the ability of sphincter preservation in patients with distal rectal cancer. Ongoing studies will identify the patients who are candidates for this therapeutic approach and the most suitable combined treatment.

Carcinoma of the pancreatic head area. Therapy: intraluminal brachytherapy.

Intraluminal brachytherapy (Il-BRT) consists in the treatment of neoplasms by the positioning of radioactive sources in the lumen of cavitary organs such as the esophagus, the trachea, the bronchi and bile ducts. This procedure has been used to deliver relatively high doses of irradiation to bile duct and periampullary carcinomas while sparing the adjacent organs. Results of a number of reports appeared in the last fifteen years document the feasibility and tolerance of the procedure. Moreover these data seem to suggest that Il-BRT is able to prolong the survival of patients undergoing biliary drainage and that its use as boost dose in external beam radiotherapy (ERT) enhances the results of the latter. Combined ERT+Il-BRT is associated to an incidence of gastrointestinal ulcerations related to the total dose delivered. Better patient selection and standardization of reference dose represent prerequisites for testing this procedure in prospective randomized trials.

Combined modality therapy in low risk (T2N0) rectal cancer.

The authors' experience with local excision (LE) and adjuvant radiotherapy in the treatment of selected cases of rectal cancer, is reported. 41 patients with distal rectal cancer underwent elective LE for cure. Selection criteria were: the site of tumor in the lower rectum, exophytic growth, maximum diameter equal to or lower than 4 cm, tumor "freely" mobile on the rectal wall, clinical staging T1-2 N0M0, histological grading G1-2. Patients shown to be T2 on definitive histology underwent adjuvant radiotherapy to the site of tumor and to pelvic lymph nodes. LE was performed via transanal route under general anesthesia. Operative mortality was 0% and morbidity 7.3%. In 37 cases (90%) surgery was considered radical and curative. The incidence of local recurrence was 5.4%, overall evidence of disease 8.1%, cancer-specific mortality 5.4% and 5-year actuarial survival 90%. The combination with radiotherapy has achieved similar results in T1 (22 cases) and T2 (15 cases) tumors. It is concluded that LE combined with radiotherapy in T2 tumors in selected cases represent a valid therapeutic alternative to more demolitive surgery.