Phase 1/2 clinical trial of interferon α2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma

Stephen A. Boorjian, Matthew I. Milowsky, Jodi Kaplan, Martin Albert, Marta Vallee Cobham, Deirdre M. Coll, Nigel P. Mongan, Gary Shelton, Daniel Petrylak, Lorraine J. Gudas, David M. Nanus

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Abstract

To evaluate the feasibility, efficacy, and biologic effects of weekly liposome-encapsulated all-trans retinoic acid (ATRA-IV) plus interferon α2b (IFN) in patients with advanced renal cell carcinoma (RCC). Twenty-six patients with metastatic RCC were treated on a phase 1/2 trial with weekly ATRA-IV and IFN SQ daily 5 d/wk. Twelve patients received ATRA-IV at three dose levels (60, 75, and 90 mg/m) according to phase 1 methodology, and 14 additional patients received 90 mg/m. Response was assessed according to an intention-to-treat analysis. Serum retinoic acid (RA) concentrations were assayed and peripheral blood mononuclear cell mRNA expression of RA and IFN-inducible genes (RARα, RARβ2, IRF1, CRABP2, and TRAIL) were examined. No dose limiting toxicities occurred at 60 mg/m; grade 3 leukopenia affected 1/6 patients at 75 mg/m, whereas 3 patients received 90 mg/m without a dose limiting toxicities. Fourteen additional patients received 90 mg/m ATRA-IV without grade 3/4 toxicity. Five of 26 (19%) patients achieved a major response, with a median duration of 14 months (range 9 to 23); 9 additional patients (41%) demonstrated stable disease or minor response lasting ≥4 months. No significant differences in serum (RA) after ATRA infusion were detected between weeks 1 and 8 of treatment. Peripheral blood mononuclear cell mRNA expression did not correlate with clinical response. The addition of weekly ATRA-IV to IFN therapy is feasible and well tolerated, resulting in sustainable increased serum (RA). This regimen demonstrates antitumor activity in metastatic RCC, and suggests ATRA-IV augments IFN therapy.

Original languageEnglish (US)
Pages (from-to)655-662
Number of pages8
JournalJournal of Immunotherapy
Volume30
Issue number6
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Keywords

  • Interferon
  • Renal cell carcinoma
  • Retinoic acid

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Boorjian, S. A., Milowsky, M. I., Kaplan, J., Albert, M., Cobham, M. V., Coll, D. M., Mongan, N. P., Shelton, G., Petrylak, D., Gudas, L. J., & Nanus, D. M. (2007). Phase 1/2 clinical trial of interferon α2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma. Journal of Immunotherapy, 30(6), 655-662. https://doi.org/10.1097/CJI.0b013e31805449a8