Phase I trial of consensus interferon in patients with metastatic renal cell carcinoma: toxicity and immunological effects.

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.