Treatment of Renal Cell Carcinoma with Escalating Doses of Alpha-lnterferon

Abstract

Forty-one patients with advanced renal cell cancer started treatment with recombinant alpha-interferon intramuscularly, beginning at a dose of 5 x 106 U x 3/week, progressively increasing doses every week, from 5 x 106 U x 3/week to 10 x 106 U x 3/ week, to the highest dose of 15 x 106 U x 3/week. No complete response was achieved, partial response was achieved in 6 (13%) patients with a median duration of 45.2 (13-134) weeks. The majority of side effects from interferon treatment evaluated according to WHO classification were seen during the first 2 months and they were fever (after interferon administration) in 95% patients, chills (51%), flu like syndrome (65%), fatigue (87%), anorexia (80%), worsening in performance status (56%), nausea and vomiting (19%), weight loss ( > 10% during therapy) (26%), leukopenia (14%), anemia (75%), neurological symptoms (43%), psychological symptoms (19%) and dyspnea (9%). The results are similar to other studies and toxicity was only moderate.

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α_2b

“…The progressively escalated doses o f IF N were scheduled in order to increase the dose with the lowest toxicity [2], Certainly this is not a comparative study to draw conclusions with regard to toxicity, but our experience so far has been postitive based on patients' com pliance.…”

“…Interferons (IFNs) have been used in the treatment o f renal cell carcinoma (R C C ) and melanoma (MEL) with variable response rates ranging from 4 to 26% [1,2]. Although responses sometimes are late and associated with unpredictable side effects, IFN s have resulted in tumor regressions that have oc curred in experimental systems and humans.…”

Combined Treatment with Low-Dose Interferon plus Vinblastine Is Associated with Less Toxicity Than Conventional Interferon Monotherapy in Patients with Metastatic Renal Cell Carcinoma

“…The response rate after treatment with vinblastine (VBL) alone may be as low as 10%. (1,2) Clinical trials of interferon-a 2b (IFN-a 2b) as monotherapy have reported response rates of 5%-20%, (3)(4)(5)(6)(7)(8) and with a combination of standard doses of IFN (16-18 3 10 6 thrice weekly) and VBL, response rates of 18% -43% have been reported. (9)(10)(11)(12)(13) One of the principal obstacles to successful treatment with IFN is early discontinuation of treatment because of adverse effects.…”

“…(9)(10)(11)(12)(13) One of the principal obstacles to successful treatment with IFN is early discontinuation of treatment because of adverse effects. (3,4) It is possible that the response rate may be increased if the tolerability of treatment could be improved. It is unclear from published data whether high-dose IFN monotherapy is more effective than low-dose therapy.…”

“…(14,15) However, clinical trials of IFN have suggested that a dose-response effect exists or that there is a threshold dose for clinical efficacy. (2)(3)(4) Therefore, attempts to reduce the adverse effects of IFN by lowering its dose may be associated with loss of efficacy. It may be possible, however, to reduce the dose of IFN and, therefore, the risk of toxicity while preserving efficacy if a second active agent is added.…”