This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Figlin, R. A. Articles by Belldegrun, A. S. Search for Related Content PubMed PubMed Citation Articles by Figlin, R. A. Articles by Belldegrun, A. S. Social Bookmarking                            What's this?

Multicenter, Randomized, Phase III Trial of CD8⁺ Tumor-Infiltrating Lymphocytes in Combination With Recombinant Interleukin-2 in Metastatic Renal Cell Carcinoma

From the University of California, Los Angeles, Los Angeles, CA; University of Washington, Seattle, WA; Cleveland Clinic Foundation, Cleveland, OH; and University of Chicago, Chicago, IL.

Address reprint requests to Robert A. Figlin, MD, FACP, University of California, Los Angeles School of Medicine, Jonsson Comprehensive Cancer Center, 10945 Le Conte Ave, Suite 2333 PVUB, Box 957059, Los Angeles, CA 90095-7059; email rfiglin{at}med1.medsch.ucla.edu

PURPOSE: To prospectively evaluate in a multicenter randomized trial the antitumor activity of CD8⁺ tumor-infiltrating lymphocytes (TILs) in combination with low-dose recombinant interleukin-2 (rIL-2), compared with rIL-2 alone, after radical nephrectomy in metastatic renal cell carcinoma patients.

PATIENTS AND METHODS: Between December 1994 and March 1997, 178 patients with resectable primary tumors were enrolled at 29 centers in the United States and Europe. Patients underwent total nephrectomy, recovered, and were randomized to receive either CD8⁺ TILs (5 x 10⁷ to 3 x 10¹⁰ cells intravenously, day 1) plus rIL-2 (one to four cycles: 5 x 10⁶ IU/m² by continuous infusion daily for 4 days per week for 4 weeks) (TIL/rIL-2 group) or placebo cell infusion plus rIL-2 (identical regimen) (rIL-2 control group). Primary tumor specimens were cultured at a central cell-processing center in serum-free medium containing rIL-2 to generate TILs.

RESULTS: Of 178 enrolled patients, 160 were randomized (TIL/rIL-2 group, n = 81; rIL-2 control group, n = 79). Twenty randomized patients received no treatment after nephrectomy because of surgical complications (four patients), operative mortality (two patients), or ineligibility for rIL-2 therapy (14 patients). Among 72 patients eligible for TIL/rIL-2 therapy, 33 (41%) received no TIL therapy because of an insufficient number of viable cells. Intent-to-treat analysis demonstrated objective response rates of 9.9% v 11.4% and 1-year survival rates of 55% v 47% in the TIL/rIL-2 and rIL-2 control groups, respectively. The study was terminated early for lack of efficacy as determined by the Data Safety Monitoring Board.

CONCLUSION: Treatment with CD8⁺ TILs did not improve response rate or survival in patients treated with low-dose rIL-2 after nephrectomy.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				T. B. Dorff, A. Goldkorn, and D. I. Quinn Review: Targeted therapy in renal cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 183 - 205. [Abstract] [PDF]

				A. Shablak, R. E. Hawkins, D. G. Rothwell, and E. Elkord T Cell-Based Immunotherapy of Metastatic Renal Cell Carcinoma: Modest Success and Future Perspective Clin. Cancer Res., November 1, 2009; 15(21): 6503 - 6510. [Abstract] [Full Text] [PDF]

				B. I. Rini Metastatic Renal Cell Carcinoma: Many Treatment Options, One Patient J. Clin. Oncol., July 1, 2009; 27(19): 3225 - 3234. [Abstract] [Full Text] [PDF]

				G. MARKEL, T. COHEN-SINAI, M. J. BESSER, K. OVED, O. ITZHAKI, R. SEIDMAN, A. J. TREVES, E. FRIDMAN, Y. KEISARI, Z. DOTAN, et al. Preclinical Evaluation of Adoptive Cell Therapy for Patients with Metastatic Renal Cell Carcinoma Anticancer Res, January 1, 2009; 29(1): 145 - 154. [Abstract] [Full Text] [PDF]

				J. Schlom, J. L. Gulley, and P. M. Arlen Paradigm Shifts in Cancer Vaccine Therapy Experimental Biology and Medicine, May 1, 2008; 233(5): 522 - 534. [Abstract] [Full Text] [PDF]

				M. Matter, V. Pavelic, D. D. Pinschewer, S. Mumprecht, B. Eschli, T. Giroglou, D. von Laer, and A. F. Ochsenbein Decreased Tumor Surveillance after Adoptive T-Cell Therapy Cancer Res., August 1, 2007; 67(15): 7467 - 7476. [Abstract] [Full Text] [PDF]

				J. Schlom, P. M. Arlen, and J. L. Gulley Cancer Vaccines: Moving Beyond Current Paradigms Clin. Cancer Res., July 1, 2007; 13(13): 3776 - 3782. [Abstract] [Full Text] [PDF]

				Q. Zhang, X. Yang, M. Pins, B. Javonovic, T. Kuzel, S.-J. Kim, L. V. Parijs, N. M. Greenberg, V. Liu, Y. Guo, et al. Adoptive Transfer of Tumor-Reactive Transforming Growth Factor-{beta}-Insensitive CD8+ T Cells: Eradication of Autologous Mouse Prostate Cancer Cancer Res., March 1, 2005; 65(5): 1761 - 1769. [Abstract] [Full Text] [PDF]

				T. M. Mekhail, R. M. Abou-Jawde, G. BouMerhi, S. Malhi, L. Wood, P. Elson, and R. Bukowski Validation and Extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in Patients With Previously Untreated Metastatic Renal Cell Carcinoma J. Clin. Oncol., February 1, 2005; 23(4): 832 - 841. [Abstract] [Full Text] [PDF]

				F. Chagnon, S. Tanguay, O. L. Ozdal, M. Guan, Z. Z. Ozen, J.-S. Ripeau, M. Chevrette, M. M. Elhilali, and L. A. Thompson-Snipes Potentiation of a Dendritic Cell Vaccine for Murine Renal Cell Carcinoma by CpG Oligonucleotides Clin. Cancer Res., February 1, 2005; 11(3): 1302 - 1311. [Abstract] [Full Text] [PDF]

				T R L Griffiths and J K Mellon Evolving immunotherapeutic strategies in bladder and renal cancer Postgrad. Med. J., June 1, 2004; 80(944): 320 - 327. [Abstract] [Full Text] [PDF]

				B. I. Rini, S. Halabi, J. Taylor, E. J. Small, and R. L. Schilsky Cancer and Leukemia Group B 90206: A Randomized Phase III Trial of Interferon-{alpha} or Interferon-{alpha} Plus Anti-Vascular Endothelial Growth Factor Antibody (Bevacizumab) in Metastatic Renal Cell Carcinoma Clin. Cancer Res., April 15, 2004; 10(8): 2584 - 2586. [Abstract] [Full Text] [PDF]

				A. Ribas, L. H. Butterfield, J. A. Glaspy, and J. S. Economou Current Developments in Cancer Vaccines and Cellular Immunotherapy J. Clin. Oncol., June 15, 2003; 21(12): 2415 - 2432. [Abstract] [Full Text] [PDF]

				E. M. Messing, J. Manola, G. Wilding, K. Propert, J. Fleischmann, E. D. Crawford, J. E. Pontes, R. Hahn, and D. Trump Phase III Study of Interferon Alfa-NL as Adjuvant Treatment for Resectable Renal Cell Carcinoma: An Eastern Cooperative Oncology Group/Intergroup Trial J. Clin. Oncol., April 1, 2003; 21(7): 1214 - 1222. [Abstract] [Full Text] [PDF]

				B. I. Rini, T. Zimmerman, W. M. Stadler, T. F. Gajewski, and N. J. Vogelzang Allogeneic Stem-Cell Transplantation of Renal Cell Cancer After Nonmyeloablative Chemotherapy: Feasibility, Engraftment, and Clinical Results J. Clin. Oncol., April 15, 2002; 20(8): 2017 - 2024. [Abstract] [Full Text] [PDF]

				R. C. Flanigan, S. E. Salmon, B. A. Blumenstein, S. I. Bearman, V. Roy, P. C. McGrath, J. R. Caton Jr., N. Munshi, and E. D. Crawford Nephrectomy Followed by Interferon Alfa-2b Compared with Interferon Alfa-2b Alone for Metastatic Renal-Cell Cancer N. Engl. J. Med., December 6, 2001; 345(23): 1655 - 1659. [Abstract] [Full Text] [PDF]

				A. C Armstrong, D. Eaton, and J. C Ewing Science, medicine, and the future: Cellular immunotherapy for cancer BMJ, December 1, 2001; 323(7324): 1289 - 1293. [Full Text] [PDF]