Purpose: The purpose of our study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities, and effects on chemokine/cytokine gene expression in peripheral blood mononuclear cells (PBMCs) of consensus IFN (CIFN).
Experimental design: Cohorts of three to six patients with metastatic renal cell carcinoma (RCC) were treated with escalating doses of CIFN (dose level I, 9.0 microg/m(2); dose level II, 15.0 microg/m(2); dose level III, 21.0 microg/m(2)) given s.c. three times weekly in 4-week cycles until progression. The cohort treated at the maximum tolerated dose was expanded to further define toxicity. An additional three patients were treated with i.v. CIFN (15.0 microg/m(2)) to evaluate route-related differences in gene expression. Cytokine and chemokine gene expression in PBMCs was assessed by reverse transcription-PCR.
Results: A total of 25 patients (18 men and 7 women) were enrolled between January 28, 1999, and November 1, 2000, at dose levels I (n = 4), II (n = 14), and III (n = 7). Dose-limiting toxicity occurred at dose level III (21 microg/m(2)) and included grade-3 or -4 respiratory distress/failure (n = 3) and hypocalcemia (n = 1) occurring within the first cycle of treatment. Other severe toxicities included grade-3 neutropenia, thrombocytopenia, fatigue, and nausea/vomiting. Studies of cytokine and chemokine gene expression in PBMCs from eight patients revealed induction of IFN-gamma, IP-10, and Mig. I.V. administration was associated with a faster induction, but of shorter duration. There were no responses; however, 24 patients had stable disease of variable duration (4-32 weeks) and received a median of three cycles of treatment (range, 1-8 cycles). Overall median survival was 13.5 months, and was 12.7 months in the previously treated patients.
Conclusion: CIFN was safely administered s.c. three times weekly at doses up to 15.0 microg/m(2). Although there were no responses, the median survival was longer than expected in a previously treated patient population with metastatic RCC.