A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

Abstract

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

Aspirin as adjuvant therapy for colorectal cancer—reinterpreting paradigms

“…20,26 Adjuvant studies Aspirin is an unlikely anticancer drug, and its emergence as an important potential adjuvant agent prompts us to reflect about how we select and design anticancer therapies for development. Aspirin has no demonstrable activity in patients with overt metastatic cancer, 53,54 and it probably would never have been detected as a potential anticancer agent by using the standard NCI-60 cancer cell line drug screening assay (a cell-based assay developed by the NCI, that evaluates drug compounds by their ability to inhibit human tumour cell growth in culture). 55 Aspirin has a lower affinity and specificity for the COX-2 isoenzyme than COX-2-selective inhibitors (such as, celecoxib), and is only weakly anti-inflammatory at standard doses.…”

Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?

“…There was no evidence that survival was different (HR 1.01, 95% CI: 0.81–1.27, P =0.09) and aspirin appeared to be well tolerated. Another trial found no evidence of a survival benefit (HR 0.91, 95% CI: 0.63–1.31, P =0.60) when 176 patients with advanced renal cell cancer received interferon- α with or without aspirin 2400 mg daily (Creagan et al , 1991). A small trial of only 66 patients evaluated 1200 mg of aspirin daily compared with placebo as adjuvant treatment for Duke's B2 and C colorectal cancer (HR for survival 0.65, 95% CI: 0.02–18.06, P =0.90) (Lipton et al , 1982).…”

Immunochemotherapy with interleukin-2, interferon- α and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study

“…In phase II studies these drugs are associated both as single agent and in combination, with a response rate between 6 and 25% and a median survival of 8-14 months (Umeda and Niijima, 1986;Creagan et al, 1991;Gore et al, 1994;Fyfe et al, 1996). In a randomized phase III study the response rates of patients treated with IL-2, IFN-α or the combination were 6.5%, 7.5% and 18.6% respectively.…”