Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced renal cell carcinoma: A cytokine working group study

Joseph I. Clark, Jessica Mehrabi, Jeffrey A. Sosman, Theodore Logan, Kim A. Margolin, Janice P. Dutcher, Walter J. Urba, Marc S. Ernstoff, David F. McDermott, Ann M. Lau, Michael B. Atkins

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A phase I/II trial was undertaken to determine the maximum tolerated dose of polyethylene glycol interferon-α-2b (PEG-IFN) with interleukin-2 (IL-2), and to evaluate the efficacy and toxicity in patients with metastatic renal cell carcinoma. Patients initially received subcutaneous PEG-IFN, 3.0 mcg/kg/wk, combined with IL-2, but owing to unexpected toxicity a revised phase I schedule ensued. Patients received 1.0, 1.5, 2.0, or 3.0 mcg/kg/wk of PEG-IFN on days 1, 8, 15, and 22; subcutaneous IL-2 was given at a dose of 5×10 IU/m every 8 hours×3 on day 1, followed daily at 5×10 IU/m days 2, 3, 4, and 5 of week 1, then 5 times per week for 3 weeks, followed by 2 weeks off. The maximum tolerated dose of PEG-IFN was 2.0 mcg/kg/wk. Fifty-four patients were enrolled. Frequent grade III/IV cardiac and neurologic toxicities led to an expanded phase I trial. Eleven serious events in 33 patients in the phase II portion led to early termination. No patient died from treatment. The overall response rate in 53 evaluable patients was 30.2% (95% confidence interval 20.5-39.9), with 2 complete responses and 14 partial responses and at least 1 response at each dose level. The median duration of response was 11 months (range, 2 to 65+ mo); median survival was 20 months (range, 2 to 71+ mo); median time to progression was 4 months. Despite clinical efficacy, the study was closed prematurely owing to excess toxicity. Although all serious adverse events resolved, this degree of toxicity is unacceptable for an outpatient treatment regimen.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalJournal of Immunotherapy
Volume30
Issue number8
DOIs
StatePublished - Nov 2007

Fingerprint

Renal Cell Carcinoma
Interferons
Interleukin-2
Outpatients
Cytokines
Maximum Tolerated Dose
Nervous System
Appointments and Schedules
Confidence Intervals
Survival
Therapeutics

Keywords

  • CWG
  • Interleukin-2
  • PEG-interferon
  • Phase I/II
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced renal cell carcinoma : A cytokine working group study. / Clark, Joseph I.; Mehrabi, Jessica; Sosman, Jeffrey A.; Logan, Theodore; Margolin, Kim A.; Dutcher, Janice P.; Urba, Walter J.; Ernstoff, Marc S.; McDermott, David F.; Lau, Ann M.; Atkins, Michael B.

In: Journal of Immunotherapy, Vol. 30, No. 8, 11.2007, p. 839-846.

Research output: Contribution to journalArticle

Clark, JI, Mehrabi, J, Sosman, JA, Logan, T, Margolin, KA, Dutcher, JP, Urba, WJ, Ernstoff, MS, McDermott, DF, Lau, AM & Atkins, MB 2007, 'Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced renal cell carcinoma: A cytokine working group study', Journal of Immunotherapy, vol. 30, no. 8, pp. 839-846. https://doi.org/10.1097/CJI.0b013e3181587977
Clark, Joseph I. ; Mehrabi, Jessica ; Sosman, Jeffrey A. ; Logan, Theodore ; Margolin, Kim A. ; Dutcher, Janice P. ; Urba, Walter J. ; Ernstoff, Marc S. ; McDermott, David F. ; Lau, Ann M. ; Atkins, Michael B. / Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced renal cell carcinoma : A cytokine working group study. In: Journal of Immunotherapy. 2007 ; Vol. 30, No. 8. pp. 839-846.
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abstract = "A phase I/II trial was undertaken to determine the maximum tolerated dose of polyethylene glycol interferon-α-2b (PEG-IFN) with interleukin-2 (IL-2), and to evaluate the efficacy and toxicity in patients with metastatic renal cell carcinoma. Patients initially received subcutaneous PEG-IFN, 3.0 mcg/kg/wk, combined with IL-2, but owing to unexpected toxicity a revised phase I schedule ensued. Patients received 1.0, 1.5, 2.0, or 3.0 mcg/kg/wk of PEG-IFN on days 1, 8, 15, and 22; subcutaneous IL-2 was given at a dose of 5×10 IU/m every 8 hours×3 on day 1, followed daily at 5×10 IU/m days 2, 3, 4, and 5 of week 1, then 5 times per week for 3 weeks, followed by 2 weeks off. The maximum tolerated dose of PEG-IFN was 2.0 mcg/kg/wk. Fifty-four patients were enrolled. Frequent grade III/IV cardiac and neurologic toxicities led to an expanded phase I trial. Eleven serious events in 33 patients in the phase II portion led to early termination. No patient died from treatment. The overall response rate in 53 evaluable patients was 30.2{\%} (95{\%} confidence interval 20.5-39.9), with 2 complete responses and 14 partial responses and at least 1 response at each dose level. The median duration of response was 11 months (range, 2 to 65+ mo); median survival was 20 months (range, 2 to 71+ mo); median time to progression was 4 months. Despite clinical efficacy, the study was closed prematurely owing to excess toxicity. Although all serious adverse events resolved, this degree of toxicity is unacceptable for an outpatient treatment regimen.",
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