Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study.

AIMS AND BACKGROUND: In 1990 the National Institutes of Health Consensus Conference recommended adjuvant combined therapy for patients with radically resected rectal cancer at high risk for relapse (ie, stage II-III). The purpose of our prospective non-randomized study was to verify the feasibility and effectiveness of postoperative radiochemotherapy in terms of improvement in disease-free and overall survival in this patient subgroup. STUDY DESIGN: From January 1990 to October 1998, 191 consecutive patients with radically resected stage II-III rectal cancer were treated. A total of 159 patients with a 24-month follow-up were assessable for toxicity and survival. Anterior resection was performed in 129 (81%) and abdomino-perineal resection in 30 (19%) patients. Fifty-four (34%) stage II and 105 (66%) stage III patients entered the study. Within 45-60 days of surgery, all patients received 5-fluorouracil chemotherapy at the dose of 500 mg/m2 as an i.v. bolus on days 1-5, every 4 weeks, for 6 cycles. Chemotherapy cycles III and IV were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy consisted of 45 Gy/25 fractions plus a boost dose of 5.4 Gy. RESULTS: After a median follow-up of 57 months (range, 25-123), overall recurrent disease was reported in 58 (36%) patients: local, systemic, and both local and systemic relapses in 12 (8%), 37 (23%) and 9 (6%) cases, respectively. According to local extension, recurrence rates were 15% and 48% in stage II and III, respectively. Five-year overall and disease-free survival were 71% and 66%, respectively. Overall survival was 87% in stage II and 62% in stage III patients, and disease-free survival was 84% and 56% in stage II and III disease, respectively. According to univariate and multivariate analyses, significant prognostic factors for better tumor control were: stage (II vs III, P <0.001), the number of involved nodes (< or = 3 vs > 3, P <0.0001), and no extracapsular node invasion (P <0.0001). The recommended dose of the combined radiochemotherapy regimen was generally well tolerated. The incidence of any > or = grade 3 acute toxicity (according to the WHO scale) was 13% diarrhea, 11% proctitis, 5% perineal dermatitis and 4% myelosuppression. Four (3%) patients had radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: The study provided recurrence rates and survival similar to other adjuvant radiochemotherapy regimens published in the literature. However, in view of the low 5-year survival rate recorded in stage III patients, a different approach should be investigated.

[Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery and with high risk of recurrence. Preliminary results of a prospective study]. / Radio-chemioterapia adiuvante nel cancro del retto radicalmente operato e con alto rischio di ricaduta. Risultati preliminari di uno studio prospettico.

UNLABELLED: INTRODUCTION MATERIAL AND METHODS: From January, 1990, to December, 1995, 138 consecutive patients with radically resected stage II and III rectal and rectosigmoid cancers were treated with adjuvant radiochemotherapy. Eighty-one patients with 24 months' follow-up were assessable. Low anterior resection (LAR) was performed in 64 (79%) patients and abdominoperineal resection (APR) in 17 (21%). Twentynine (36%) stage II and 52 (64%) stage III patients entered the study. Within 45-60 days from surgery all patients received 5-Fluorouracil chemotherapy at the dose of 500 mg/m2/iv/d 1-5, every 4 weeks, for six cycles. Chemotherapy cycles 3 and 4 were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy total dose consisted of 45 Gy/1.8 Gy/day administered in 5 weeks with 18 MV photon beam to the pelvis with the four field "box" technique. Perineal scar was encompassed only after APR. A boost dose of 5.4 Gy to the tumor bed was given in 3 fractions of 1.8 Gy. Median follow-up was 37 months (range: 24-74 months). RESULTS AND DISCUSSION: Overall recurrent disease was reported in 28 of 81 patients (34%): local, systemic and both local and systemic relapses in 9 (11%), 14 (17%) and 5 (6%) cases, respectively. According to local extension, recurrence rates were 10% and 48% in stages II and III, respectively. Five-year overall and disease-free actuarial survivals were 64% and 61%, respectively. Median time to relapse was 15 months (range: 7-43 months). Significant prognostic factors for better tumor control were: stage (II vs III), disease site (proximal vs distal rectum), the surgical procedure (LAR vs APR), the number of involved nodes (< or = 4 vs > 4) and no extracapsular node invasion. The recommended dose of combined radiochemotherapy regimen used in this trial was generally well tolerated. The incidence of any grade > or = 3 acute toxicity (according to WHO grading) was 20% diarrhea, 6% tenesmus and 4% myelosuppression. Five (6%) patients had cronic diarrhea and other 3 (4%) radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: This study seems to provide similar survival and recurrence notes to other radio-chemotherapy regimens published in the literature. However, a more aggressive approach is warranted in stage III patients considering the low 5-year survival recorded.

Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer.

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T. In the present study we adopted a treatment schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60 mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T (30 mg/day). We obtained a 13% response rate with a median duration of response of 8 months (range 4-16 m). All the responses occurred in pts whose disease progressed after an initial response to T. Stabilisation of disease was observed in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN-beta in the treatment of breast cancer remains investigational and the optimal scheduling still undetermined.