Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies.

PURPOSE: To compare acute toxicity, tumor response, and sphincter preservation in three schedules of concurrent chemoradiation in resectable transmural and/or node-positive extraperitoneal rectal cancer. PATIENTS AND METHODS: Between 1990 and 1999, 163 consecutive patients were treated according to the following combined modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32 with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and 1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy). RESULTS: Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201). In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%, 70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of patients, respectively. Pathologic complete response was recorded in 9% (FUMIR), 23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm, and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm. Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two series: a partial response was observed in 62/81 (77%) patients with FUMIR treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively. The pathologic complete response rate was statistically higher in the PLAFUR series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%) patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment. The perioperative morbidity was statistically lower with PLAFUR: a perioperative morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by 9/80 (11%) patients with PLAFUR treatment (p = 0.042). CONCLUSION: In our experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic response rate without increasing acute toxicity and perioperative morbidity. The use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar response rate compared to 4-day infusion (PLAFUR-4).

Topical issues in the treatment of rectal cancer: economic and organizational aspects of concomitant radiochemotherapy.

Concomitant radiochemotherapy in patients with locally advanced rectal carcinoma has been shown to be useful in improving local control and survival in operated patients and in favoring sphincter preservation when administered before surgery. Together with the search for less toxic combinations, cost-analysis of radiochemotherapy has become topical also in consideration of new generation drugs. In this study the analysis was carried out by comparing the costs for 4 different combined modalities in the dual perspective of the payer (the National Health Service) and the provider (the Hospital). Based on their characteristic of treatment and innovative aspects, the following combinations were examined: external beam radiotherapy (ERT) 50.4 Gy + 5FU bolus; ERT 50.4 Gy + 5FU protracted infusion; ERT 50.4 Gy + 5FU continuous infusion, week 1 and 5; ERT 50.4 Gy+ Tomudex bolus. Costs were evaluated based on the frequency and type of specific services provided in therapeutic protocols: the positioning of central venous catheter, time of stay in day-hospital or hospital ward and the cost of drugs. Calculations were carried out based on an "ideal" patient of 1.7 sqm body surface. Costs were based on out patient rates, DRGs and the official drug list valid to September 1999. As for day-hospital costs afforded by the payer it is observed that the most expensive combinations are bolus and continuous infusion followed by protracted infusion; Tomudex, is the most economic. As for hospital costs afforded by the provider, it is observed that the most expensive combination is continuous infusion followed by protracted infusion, bolus administration and Tomudex. In conclusion, doctors are increasingly involved in the economic and organizational aspects of therapeutic decisions; however, the patient's needs should be kept in mind; apart from the therapeutic benefits, lower toxicity and ready use of treatments are amongst the patient's needs. The analysis of the patient's satisfaction is still lacking suitable means of evaluation, however it should be defined and carefully studied for an exhaustive evaluation of the impact of combined modality therapy.