Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer.

PURPOSE: To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFN alpha 2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of 245 previously untreated ACC patients were randomized to receive either IFN alpha 2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/ 5-FU), or 5-FU alone at the same dose schedule (5-FU). RESULTS: There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/ 5-FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens. CONCLUSION: The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.

Long-term results with MACOP-B in the treatment of aggressive non-Hodgkin's lymphomas. The experience in Brazil.

From October 1984 to December 1989, 59 patients with aggressive non-Hodgkin's lymphomas (diffuse mixed, diffuse large cell, and immunoblastic) were treated with MACOP-B. All patients were previously untreated and most of them had advanced disease. Complete response (CR) was observed in 66%. Actuarial overall survival, failure-free survival (FFS), and relapse-free survival at 8 years were 54%, 52%, and 81%, respectively, with a median follow-up of 76 months (range: 28-92 months). The presence of B symptoms influenced significantly the CR rate, while FFS was affected by B symptoms, bone marrow involvement, and number of extranodal sites. Toxicity was high, with mucositis grade 2 or 3 occurring in 70%, leukopenia grades 3 or 4 in 80%, and death in 11.8% of the patients. MACOP-B was active in the treatment of aggressive non-Hodgkin's lymphomas, mainly in patients with few poor-prognosis factors, but other less toxic regimens would be more appropriate for this population. For poor-prognosis patients, new therapeutic modalities are necessary.

A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus.

From September 1982 to December 1985, 59 previously untreated patients with Stage II squamous cell carcinoma of the thoracic esophagus were randomly assigned to receive radiation therapy (RT) alone versus the concomitant use of RT and chemotherapy (CT) with 5-fluorouracil (5-FU), mitomycin C, and bleomycin (RT + CT). Thirty-one patients were randomized to the RT regimen and 28 to the RT + CT regimen. The complete local response rate was 58% for the RT group and 75% for the RT + CT group (P = 0.77). The median duration of response was 8 months for both groups. The overall 5-year survival rates were 6% and 16% (P = 0.16) for the RT and RT + CT groups, respectively. Acute toxicities were more pronounced in the RT + CT group. This clinical trial did not detect a difference in outcome with combined-technique therapy. This result must be interpreted with caution because of the small number of patients entered in this trial. Confirmation of the value or lack of value for combined therapy will require additional larger clinical trials.