Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients.

PURPOSE: Although the role of radiotherapy (RT) after mastectomy in reducing the local relapse rate is well established, its impact on overall survival is strongly questioned. Up to 70% of patients will not benefit from additional RT, and a "wait and see" policy is often adopted. Establishment of short, still safe, and effective RT regimens would render adjunctive radiotherapy more appealing. We evaluated the toxicity and efficacy of a Hypofractionated and intensively Accelerated RT regimen supported with amifostine Cytoprotection (HypoARC) in a cohort of 72 high-risk breast cancer patients treated with modified mastectomy or conservative surgery and FEC (5-fluorouracil/epirubicin/cyclophosphamide) chemotherapy. PATIENTS AND METHODS: A high dose of amifostine, 1,000 mg, was given as a 5-min i.v. infusion before each of the 12 consecutive fractions of RT (4 x 3.5 Gy/fraction and 8 x 4 Gy/fraction, 1 fraction/day, 5 fractions/week). The breast or chest wall, as well as supraclavicular and axillary area, was included in the RT fields. The follow-up of patients ranged from 18 to 42 months (median, 28 months). Alkaline phosphatase (AF) expression was assessed immunohistochemically in normal and cancerous breast tissues. RESULTS: Ninety-two percent of patients successfully completed the regimen, the only side effects being mild nausea and asthenia. In 7% of patients, amifostine was interrupted because of a rash/fever reaction. A dramatic reduction in acute skin toxicity was noted (p < 0.0001). Acute pneumonitis, as well as late toxicity in breast, chest wall, axillary, and lung tissue, was lower with the HypoARC regimen, although not significantly, than with the standard fractionation regimen used to treat two matched control cohorts. Both HypoARC and standard RT significantly reduce the local relapse rate (p < 0.0001), although the local relapse-free and overall survival times were marginally better for the HypoARC group of patients (p > 0.09). AF showed a mixed nuclear/cytoplasmic pattern of expression in the epithelial, endothelial, and stromal component of the normal breast and benign lesions, whereas an impressive loss of AF expression was noted in in situ and invasive breast cancer and tumoral stroma. CONCLUSIONS: The HypoARC regimen is convenient for both patients and radiotherapy departments. The regimen is well tolerated and shows a significantly better profile in terms of early toxicity; a reduced rate of late sequel may be expected. The local relapse rate is as low as that expected from conventional RT. The absence of AF expression in cancer cells and tumoral stroma is probably a major reason for the selective protection of normal breast tissue by amifostine.

Amifostine, in a reduced dose, protects against severe diarrhea associated with weekly fluorouracil and folinic acid chemotherapy in advanced colorectal cancer: a pilot study.

Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m(2). The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m(2) was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m(2), diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability.

Adjuvant systemic therapy protocol for Dukes' B2 and C resectable colon carcinoma.

AIMS AND BACKGROUND: Trials of adjuvant systemic therapy in high risk patients with Dukes' B2 and C colon cancer utilizing 5-fluorouracil-based regimens have been ongoing since the 1960s. The aim of this study was to compare the combination of 5-FU and leucovorin with the combination of 5-FU and alfa-2b interferon (IFN) in patients who had undergone "curative" resection foronocarcinoma. STUDY DESIGN: A total of 322 patients with histologically proven adenocarcinoma of the colon, Dukes' stage B2 and C, were entered in the study. They were randomized to A) leucovorin 20 mg/m2 rapid intravenous injection and 5-FU 425 mg/m2 IV days 1-5 every 28 days for six cycles or B) 5-FU 600 mg/m2 24-hour infusion for five days, then 600 mg/m2 IV once a week and IFN 5 MU subcutaneously three times a week for six months. RESULTS: There was no statistically significant difference in either disease-free survival or overall survival. Toxicity was the same in the two groups with the exception of flu-like syndrome, which was universal in IFN-treated patients. CONCLUSIONS: There was no difference in disease-free survival or overall survival between the two combinations in any patient subset. Toxicity was greater with the 5-FU+IFN combination because of the flu-like syndrome. These data do not support the use of IFN in combination with 5-FU as systemic adjuvant therapy for patients with locally advanced colon carcinoma.