Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 12, 2003 - Issue 4
Submit an article Journal homepage
29
Views
12
CrossRef citations to date
0
Altmetric
Review

Novel therapies for renal cell carcinoma – an update

Mayer Fishman H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, MCC 4035, 12902 Magnolia Drive, Tampa, FL 33612, USA
&
Scott Antonia H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, MCC 4035, 12902 Magnolia Drive, Tampa, FL 33612, USA
Pages 593-609 | Published online: 02 Mar 2005

Bibliography

  • KEILHOLZ U, WEBER J, FINKE JH et al.: Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the Society for Biological Therapy. Immunothec (2002) 25(2):97–138. A comprehensive discussion of ways to assay the immune system.
  • AMATO RJ: Chemotherapy for renal cell carcinoma. Semin. Oncol (2000) 27(2):177–186.
  • MOTZER RI, RUSSO P: Systemic therapy for renal cell carcinoma. J. Um]. (2000) 163(2):408–417.
  • FISHMAN M, SEIGNE J, ANTONIA S: Novel therapies for renal cell carcinoma. Expert Opin. Investig. Drugs (2001) 10:1033–1044.
  • •The previous review of this series, which has more discussion of surgical decision making and VHL physiology.
  • RINI BL, VOGEIZANG NJ, DUMAS MC, WADE JL, TABER DA,STADLER WM: Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J. Clin. Oncol (2000) 18(12):2419–2426.
  • GEORGE CM, VOGELZANG NJ, RINI BI et al.: A Phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma. Ann. Oncol (2002) 13(1):116–120.
  • RYAN CW, VOGELZANG NJ, STADLER WM: A Phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma. Cancer (2002) 94(10):2602–2609.
  • DESAI AA, VOGELZANG NJ, RINI B et al.: A Phase II trial of weekly intravenous gemcitabine (G) with prolonged continuous infusion 5-fluorouracil (F) and oral thalidomide (T) in patients with metastatic renal cell cancer (mRCC). Proc. Am. Soc. Clin. Onc. (2001) (Abstract 2448).
  • WENZEL C, LOCKER GJ, SCHMIDINGER M et al.: Capecitabine in the treatment of metastatic renal cell carcinoma failing immunotherapy. Am. J. Kidney Dis. (2002) 39(1):48–54.
  • CHANG DZ, OLENCKI T, BUDD GT et al.: Phase I trial of capecitabine in combination with interferon alpha in patients with metastatic renal cancer: toxicity and pharmacokinetics. Cancer Chemother. Pharmacol (2001) 48(6):493–498.
  • PARK DK, RYAN CW, DOLAN ME, VOGELZANG NJ, STADLER WM: A Phase II trial of oral temozolomide in patients with metastatic renal cell cancer. Cancer Chemother: Pharmacol (2002) 50(2):160–162.
  • SUNKARA UK: A Phase II trial of temozolomide and interferon-a in patients with advanced renal cell carcinoma. Proc. Am. Soc. Clin. Onc. (2001) (Abstract 2449).
  • VIS N, VAN DER GAAST A, VAN RHIJN G et al.: A Phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy. Cancer Chemother: Pharmacol (2002) 49(4):342–345.
  • BERG WJ, SCHWARTZ L, YU R, MAZUMDAR M, MOTZER RJ: Phase II trial of irofulven (6-hydroxymethylacylfulvene) for patients with advanced renal cell carcinoma. Invest. New Drugs (2001) 19(4):317–320.
  • PYRHONEN S, SALMINEN E, RUUTU M et al.: Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. Clin. Oncol (1999) 17:2859–2867.
  • •The positive IFN randomised study.
  • STERNBERG J, BERRY M, GREGURICH M, BOXER M, ANTHONY S: Phase-II trial of single-agent, weekly docetaxel in advanced or metastatic renal cell carcinoma (MRCC). Proc. Am. Soc. Clin. Onc. (2001) (Abstract 2379).
  • BRADLEY MO, WEBB NL, ANTHONY FH et al.: Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clin. Cancer Res. (2001) 7(10):3229–3238.
  • IBRAHIM D, HUSSAIN M, LORUSSO P, FLAHERTY L: Rebeccamycin analog (BMY-27557-14) in renal cell cancer (RCC): preliminary results of a Phase II trial. Proc. Am. Soc. Clin. Onc. (2001) (Abstract 2373).
  • SKUBITZ K: A Phase III trial of pegylated liposomal doxorubicin (Doxil) in renal cell carcinoma, mesothelioma, and head and neck cancer. Proc. Am Soc Clin Onc. (2000) (Abstract 1693).
  • PROTHEROE A, SRINIVASAN M, SMITH C et al.: A Phase II trial of bryostatin-1 in patients with advanced renal cancer. Proc. Am. Soc. Clin. Onc. (2002) (Abstract 2495).
  • FRIEDLAND D, LEON L, MANOLA J, DUTCHER JP, ROTH B, WILIDING G: Carboxyamidotriazole (CAI) in patients with advanced renal cell cancer (RCC) refractory to immunotherapy: an ECOG Phase II trial. Proc. Am. Soc. Clin. Onc. (2002) (Abstract 2424).
  • LIU Z, SMYTH FE, RENNER C et al: Anti-renal cell carcinoma chimeric antibody G250: cytokine enhancement of M vitro antibody-dependent cellular cytotoxicity. Cancer Immunol Immunother. (2002) 51(3):171–177.
  • STEFFENS MG, BOERMAN OC, DE MULDER PH et al: Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250. Clin. Cancer Res. (1999) 5(10, Suppl. 0:32685-3274S.
  • WISEMAN GA, SCOTT AM, LEE F et al: Chimeric G250 (cG250) monoclonal antibody Phase I dose escalation trial in patients with advanced renal cell carcinoma. Proc. Am. Soc. Clin. Oncol 20\(Part 1):257a (Abstract 1027).
  • LUITEN RM, CONEY LR, FLEUREN GJ, WARNAAR SO, LITVINOV SV: Generation of chimeric bispecific G250/anti-CD3 monoclonal antibody, a tool to combat renal cell carcinoma. Br. J. Cancer (1996) 74(5):735–744.
  • GRABMAIER K, VISSERS JL, DE WEIJERT MC et al.: Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250. Int. J. Cancer (2000) 85(6):865–870.
  • TSO CL, ZISMAN A, PANTUCK A et al: Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor. Cancer Res. (2001) 61(21):7925–7933.
  • DRUCKER BJ, SCHWARTZ L, MARION S, MOTZER R: Phase II trial of ZD1839 (Iressa), an EGF receptor inhibitor, in patients with advanced renal cell carcinoma. Proc. Am. Soc. Clin. Oncol (2002) (Abstract 720).
  • SCHWARTZ G, DUTCHER JP, VOGELZANG NJ et al.: Phase II clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC). Proc. Am. Soc. Clin. Oncol (2002) (Abstract 91).
  • YANG JC, HAWORTH L, STEINBERG SM, ROSENBERG SA, NOVOTNY W: A randomized double-blind placebo-controlled trial of bevacizumab (anti-VEGF antibody) demonstrating a prolongation in time to progression in patients with metastatic renal cancer. Proc. Am. Soc. Clin. Oncol (2002) (Abstract 15).
  • •The data have been updated in various settings. A phase III study to confirm the fmdings are planned.
  • LARA P, QUINN D, MARGOLIN K et al: Angiogenesis inhibition in renal cell carcinoma (RCC): a Phase II California Cancer Consortium study of 5U5416 + interferon with biologic & imaging correlates. Proc. Am. Soc. Clin. Oncol (2002) (Abstract 736).
  • GRIFFIN RJ, WILLIAMS BW, WILD R et al.: Simultaneous inhibition of the receptor kinase activity of vascular endothelial, fibroblast, and platelet-derived growth factors suppresses tumor growth and enhances tumor radiation response. Cancer Res. (2002) 62(6):1702–1706.
  • HEINRICH MC, BLANKE CD, DRUKER BJ, CORLESS CL: Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. Clin. Oncol (2002) 20(6):1692–1703.
  • BRAHMER J, KELSEY S, SCIGALLA P et al.: A Phase I study of 5U6668 in patients with refractory solid tumors. Proc. Am. Soc. Clin. Oncol (2002) (Abstract 335).
  • WEDGES, OGILVIE D, DUKES M et al: ZD6474 inhibits Vascular Endothelial Growth Factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. (2002) 62:4645–4655.
  • KARP DD, TOLCHER A, HEALEY D et al.: Preliminary pharmacokinetic (PK) characteristics of an oral vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), CP-547,632 in patients (pts) with advanced solid tumors. American Association for Cancer Research Annual Meeting, San Francisco, CA, USA (2002) (Abstract 2753).
  • DREVS J, HOFMANN I, HUGENSCHMIDT H et al.: Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. (2000) 60(17):4819–4824.
  • DREVS J, MULLER-DRIVER R, WITTIG C et al: PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res. (2002) 62(14):4015–4022.
  • DALIANI DD, PAPANDREOU CN, THALL PF et al.: A pilot study of thalidomide in patients with progressive metastatic renal cell carcinoma. Cancer (2002) 95(4):758–765.
  • ESCUDIER B, LASSAU N, COUANET D et al: Phase II trial of thalidomide in renal-cell carcinoma. Ann. Oncol (2002) 13(7):1029–1035.
  • MOTZER RJ, BERG W, GINSBERG M et al.: Phase II trial of thalidomide for patients with advanced renal cell carcinoma. Clin. Oncol (2002) 20(1):302–306.
  • STEBBING J, BENSON C, EISEN T et al.: The treatment of advanced renal cell cancer with high-dose oral thalidomide. Br: J. Cancer (2001) 85(7):953–958.
  • EISEN T, BOSHOFF C, MAK let al.: Continuous low dose Thalidomide: a Phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br. J. Cancer (2000) 82(4):812–817.
  • AMATO R, BREHENY S, TRACY E: Phase I/II study of thalidomide + interleukin II (IL-2) for patients with metastatic renal cell carcinoma. Proc. Am. Soc. Clin. Oncol (2002) (Abstract 759).
  • ••Combinations of IL-2 and thalidomidewill undoubtedly be tested further.
  • OLENCKI T, DREICER R, ELSONP, WOOD L, BUKOWSKI R: Phase I trial of thalidomide and interleukin-2 (IL-2) in patients (pts) with metastatic renal cell carcinoma (RCC). Proc. Am. Soc. Clin. Oncol (2002) (Abstract 2430).
  • ••Combinations of IL-2 and thalidomidewill undoubtedly be tested further.
  • STADLER WM, KUZEL T, SHAPIRO C, SOSMAN J, CLARK J, VOGEIZANG NJ: Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma. J. Clin. Oncol (1999) 17(8):2541–2545.
  • O'REILLY MS, BOEHM T, SHING Y et al.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell (1997) 88(2):277–285.
  • HERBST RS, HESS KR, TRAN HT et al.: Phase I study of recombinant human endostatin in patients with advanced solid tumors. .1 Clin. Oncol (2002) 20(18):3792–3803.
  • GINGRAS D, RENAUD A, MOUSSEAU N, BEAULIEU E, KACHRA Z, BELIVEAU R: Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound. Anti-Cancer Res. (2001) 21(1A):145–155.
  • BELIVEAU R, GINGRAS D, KRUGER EA et al.: The antiangiogenic agent neovastat (AE-941) inhibits vascular endothelial growth factor-mediated biological effects. Clin. Cancer Res. (2002) 8(4):1242–1250.
  • LLIOPOLIS 0, ENG C: Genetic and clinical aspects of familiar renal neoplasms. Semin. Oncol (2000) 27(2):138–149.
  • JIANG F, DESPER R, PAPADIMITRIOU CH et al: Construction of evolutionary tree models for renal cell carcinoma from comparative genomic hybridization data. Cancer Res. (2000) 60(22):6503–6509.
  • KONDO K, YAO M, YOSHIDA M, KISHIDA T, SHUIN T, MIURA T: Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer (2002) 34(1):58–68.
  • MEYER AJ, HERNANDEZ A, FLORL AR et al.: Novel mutations of the von hippel-lindau tumor-suppressor gene and rare DNA hypermethylation in renal-cell carcinoma cell lines of the clear-cell type. hat. J. Cancer (2000) 87(5):650–653.
  • MANDRIOTA SJ, TURNER KJ, DAVIES DR et atHIF activation identifies early lesions in VHL kidneys. Evidence for site-specific tumor suppressor function in the nephron. Cancer Cell (2002) 1(5):459–468.
  • CLIFFORD SC, PROWSE AH, AFFARA NA, BUYS CH, MAHER ER: Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer (1998) 22(3):200–209.
  • MARTINEZ A, FULLWOOD P, KONDO K et al.: Role of chromosome 3p12-p21 tumor suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis. Mol. Pathol (2000) 53(3):137–144.
  • MORRISSEY C, MARTINEZ A, ZATYKA M et al.: Epigenetic inactivation of the RASSF1A tumor suppressor gene in both clear cell and papillary renal cell carcinoma. Cancer Res. (2001) 61(19):7277–7281.
  • DREIJERINK K, BRAGA E, KUZMIN I et al.: The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc. Natl. Acad. Sci. USA (2001) 98(13):7504–7509.
  • YOON JH, DAMMANN R, PFEIFER GP: Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. Int. J. Cancer (2001) 94(2):212–217.
  • MAXWELL PH, WIESENER MS, CHANG GW et al: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature (1999) 399(6733):271–275.
  • COCKMAN ME, MASSON N, MOLE DR et al.: Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. (2000) 275(33):25733–25741.
  • KRIEG M, HMS R, BRAUCH H, ACKERT, FLAMME I, PLATE KH: Upregulation of hypwda-inducible factors H1F-lalpha and H1F-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene (2000) 19(48):5435–5443.
  • TANIMOTO K, MAKINO Y, PEREIRA T, POELLINGER L: Mechanism of regulation of the hypoxiainducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO (2000) 19(16):4298–4309.
  • RICHARD DE, BERRA E, GOTHIE E, ROUX D, POUYSSEGUR J: p42/44 Mitogen-activated protein kinases phosphorylate hypoxia-inducible factor la (HIF-1a) and enhance the transcriptional activity of HIF-1. j. Bid. Chem. (1999) 274(46):32631–32637.
  • BINDRA RS, VASSELLI JR, STEARMAN R, LINEHAN WM, KLAUSNER RD: VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells. Cancer Res. (2002) 62(11):3014–3019.
  • HANAI J, DHANABAL M, KARUMANCHI SA et al.: Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin Dl. Biol. Chem. (2002) 277(19):16464–16469.
  • KAWAII S, TOMONO Y, OGAWA K, SUGIURA M, YANO M, YOSHIZAWA Y: The antiproliferative effect of coumarins on several cancer cell lines. Anti-Cancer Res. (2001) 21(2A):917–923.
  • ZHU Z, JIANG W, GANTHER HE, THOMPSON HJ: Mechanisms of cell cycle arrest by methylseleninic acid. Cancer Res. (2002) 62(1):156–164.
  • CHEN B, ZHANG XY, ZHANG YJ, ZHOU P, GU Y, FAN DM: Antisense to cyclin DI reverses the transformed phenotype of human gastric cancer cells. World J. Gastroenterol (1999) 5(1):18–21.
  • ANANTH S, KNEBELMANN B, GRUNING W: Transforming growth factor beta], is a target for the von Hippel-Lindau tumor suppressor and a critical growth factor for clear cell renal carcinoma. Cancer Res. (1999) 59(9):2210–2216.
  • MASSAGUE J, WOTTON D: Transcriptional control by the TGFbeta/ Smad signaling system. EMBO J. (2000) 19(8):1745–1754.
  • STROBL H, KNAPP W: TGF-betal regulation of dendritic cells. Microbes Infect. (1999) 1(15):1283–1290.
  • HALLIDAY GM, LE S: Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin. Int. Immunol (2001) 13(9):1147–1154.
  • KNEBELMANN B, ANANTH S, COHEN HT, SUKHATME VP: Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res. (1998) 58(2):226–23 I.
  • TURNER KJ, MOORE JW, JONES A et al.: Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. (2002) 62(10):2957–2961.
  • SCHRAML P, STRUCKMANN K, HATZ F et al.: VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J. Pathol (2002) 196(2):186–193.
  • IGARASHI H, ESUMI M, ISHIDA H, OKADA K: Vascular endothelial growth factor overexpression is correlated with von Hippel-Lindau tumor suppressor gene inactivation in patients with sporadic renal cell carcinoma. Cancer (2002) 95(1):47–53.
  • •One of several articles confirming a linkage between VHL and VEGF pathophyisology.
  • KONDO K, KLCO J, NAKAMURA E, LECHPAMMER M, KAELIN WG: Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell (2002) 1(3):237–246.
  • MARANCHIE JK, VASSELLI JR, RISS J, BONIFACINO JS, LINEHAN WM, KLAUSNER RD: The contribution of VHL substrate binding and HIF 1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell (2002) 1(3):247–255.
  • SEAGROVES T, JOHNSON RS: Two HIFs may be better than one. Cancer Cell (2002) 1(3):211–213.
  • LAUGHNER E, TAGHAVI P, CHILES K, MAHON PC, SEMENZA GL: HERZ (neu) signaling increases the rate of hypoxia-inducible factor 1 alpha (HIF-1 alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Ma Cell. Biol. (2001) 21(12):3995–4004.
  • SEMENZA GL: Hypoxia-inducible factor 1: master regulator of 02 homeostasis. Curr. Opin. Genet. Dev. (1998) 8(5):588–594.
  • KOSHIKAWA N, TAKENAGA K, TAGAWA M, SAKIYAMA S: Therapeutic efficacy of the suicide gene driven by the promoter of vascular endothelial growth factor gene against hypoxic tumor cells. Cancer Res. (2000) 60(11):2936–2941.
  • RUAN H, WANG J, HU L, UN CS, LAMBORN KR, DEEN DF: Killing of brain tumor cells by hypwda-responsive element mediated expression of BAX. Neoplasia (1999) 1(5):431–437.
  • ISAACS JS, JUNG YJ, MIMNAUGH EG et al.: Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J. Biol. Chem. (2002) 277(33):29936–29944.
  • UDAI B: Phase I trial of the heat shock protein 90 (HSP9 0) inhibitor 1 7-allylamino 1 7-demethoxy-geldanamycin (17AAG): pharmacokinetic (PK) profile and pharmacodynamic (PD) endpoints. Proc. Am. Soc. Clin. Oncol (20 0 1) (Abstract 326).
  • ZATYKA M, DA SILVA NE CLIFFORD SC et al.: Identification of cyclin DI and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin DI genotype as a modifier in von Hippel-Lindau disease. Cancer Res. (2002) 62(13):3803–3811.
  • CALDWELL MC, HOUGH C, FURER S, LINEHAN WM, MORIN PJ, GOROSPE M: Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFalpha cytotoxicity. Oncogene (2002) 21(6):929–936.
  • BOER JM, HUBER WK, SULTMANN H et al.: Identification and classification of differentially expressed genes in renal cell carcinoma by expression profiling on a global human 31,500-element cDNA array. Genome Res. (2001) 11(11):1861–1870.
  • ••The citation, and the accompanyingwebsite (ref [202]) provide access to a large amount of primary data. More complex data or this type may be anticipated in the coming years.
  • ADAMS J: Development of the proteasome inhibitor PS-341. Oncologist (2002) 7(1):9–16.
  • SENDEROWICZ AM, HEADLEE D, STINSON SF et al.: Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J. Clin. Oncol (1998) 16(9):2986–2999.
  • SENDEROWICZ AM: The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist (2002) 7\(Suppl. 2):12–19.
  • KELLAND LR: Flavopiridol, the first cyclin-dependent kinase inhibitor to enter the clinic: current status. Expert Opin. Investig. Drugs (2000) 9(12):2903–2911.
  • PIZZOCARO G, PIVA L, COLAVITA M et al.: Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J. Clin. Oncol (2001) 19(2):425–431.
  • ••A negative study addressing a frequentdiscussion issue.
  • RAVAUD A, DELVA R, GOMEZ F et al: Groupe Francais d'Immunotherapie.Subcutaneous interleukin-2 and interferon alpha in the treatment of patients with metastatic renal cell carcinoma-Less efficacy compared with intravenous interleukin-2 and interferon alpha. Results of a multicenter Phase II trial from the Groupe Francais d'Immunotherapie. Cancer (2002) 95(11):2324–2330.
  • ATZPODIEN J, KIRCHNER H, ILLIGER HJ: IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br: J. Cancer (2001) 85:1130–1136.
  • •One of the highest response frequencies identified in an out-patient study, but still a non-randomised study.
  • NEGRIER S, ESCUDIER B, LASSET C et al.: Recombinant human interleukin-2,recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais dlmmunotherapie. N Engl. I Med. (1998) 338(18):1272–1278.
  • WEISS GR, MARGOLIN KA, ARONSON FR et al.: A randomized Phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J. Clin. Oncol. (1992) 10(2):275–281.
  • DILLMAN RO, WIEMANN MC, BURY MJ, CHURCH C, DEPRIEST C: Hybrid high-dose bolus/continuous infusion interleukin-2 in patients with metastatic renal cell carcinoma: a Phase II trial of the National Biotherapy Study Group. Cancer Biother. Radiophann. (1997) 12(1):5–11.
  • CLARK JI, KUZEL TM, LESTINGI TM et al.: A multi-institutional Phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population. Ann. Oncol. (2002) 13(0606–613.
  • NERI B, DONI L, GEMELLI MT et al.: Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer. J. Urol. (2002) 168(3):956–958.
  • BERG WJ, NANUS DM, LEUNG A et a/.: Up-regulation of retinoic acid receptor beta expression in renal cancers in vivo correlates with response to 13-cis-retinoic acid and interferon alpha-2a. ChB. Cancer Res. (1999) 7:1671–1675.
  • HOFFMAN AD, ENGELSTEIN D, BOGENRIEDER T et al: Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid. Clin. Cancer Res. (1996) 6:1077–1082.
  • JAREMTCHUK AV, AMAN EF, PONCE W et al: Low activity of 13-cis-retinoic acid plus interferon alpha 2a in advanced renal cell carcinoma. Am. J. Clin. Oncol. (2002) 25(2):123–125.
  • ALMAND B, CLARK JI, NIKITINA E et al.: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol. (2001) 166(1):678–689.
  • ••One of many details emerging on howcancers subdue the immune response.
  • OH WK, MANOLA J, GEORGE DJ, FIERMAN A, FONTAINE-ROTHE P: A Phase II trial of interferon-alpha and toremifene in advanced renal cell cancer patients. Cancer Invest. (2002) 20(2):186–191.
  • HANSSON M, HERMODSSON S, BRUNE M et al.: Histamine protects T cells and natural killer cells against oxidative stress. J. Interferon Cytokine Res. (1999) 19(10):1135–1144.
  • AGARWALA SS, GLASPY J, O'DAY SJ et al.: Results from a randomized Phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma. J. Clin. Oncol. (2002) 20:125–133.
  • URBA WJ, ALVORD WG: Are all hypotheses generated before data analysis prospective? Clin. Oncol. (2002) 20:1431–1433.
  • AGARWALA S, HELLSTRAND K, NAREDI P: Interleukin-2 and histamine dihydrochloride in metastatic melanoma. Clin. Oncol. (2002) 20:3558–3559.
  • HOFFMAN DM, FIGLIN RA: Intratumoral interleukin 2 for renal-cell carcinoma by direct gene transfer of a plasmid DNA/DMRIE/DOPE lipid complex. World .1. Urol. (2000) 18(2):152–156.
  • MOTZER RJ, RAKHIT A, GINSBERG M: Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. Clin. Oncol (2001) 19:1312–1319.
  • •A new agent that is on the market for hepatitis, and will continue to develop.
  • MOTZER RJ, RAKHIT A, THOMPSON J et al.: Phase II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma. Ann. Oncol. (2002) 13(11):1799–1805.
  • •A new agent that is on the market for hepatitis, and will continue to develop.
  • YANG JC,TOPALIAN SL, SCHWARTZENTRUBER DJ: The use of polyethylene glycol-modified interleukin-2 (PEG-IL-2) in the treatment of patients with metastatic renal cell carcinoma and melanoma. A Phase I study and a randomized prospective study comparing IL-2 alone versus IL-2 combined with PEG-IL-2. Cancer (1995) 76:687–694.
  • KEDAR E, GUR H, BABAI I: Delivery of cytokines by liposomes: hematopoietic and immunomodulatory activity of interleukin-2 encapsulated in conventional liposomes and in long-circulating liposomes. Immunother. (2000) 23:131–145.
  • SHANAFELT AB, LIN Y, SHANAFELT MC: AT-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo. Nat. Biotechnol (2000) 18:1197–1202.
  • SCHMIDINGER M, STEGER G, WENZEL C: Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a Phase II J. Immunother. (2001) 24:257–262.
  • SCHMIDINGER M, STEGER G, WENZEL C: Sequential administration of interferon gamma and interleukin-2 in metastatic renal cell carcinoma: results of a Phase II trial. Austrian Renal Cell Carcinoma Study Group. Cancer Immunol. Immunother. (2000) 49:395–400.
  • DELIMA M, AMATO RJ, JACKSON A: Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma. Cancer Biothec Radiopharm. (1997) 12:365–370.
  • ELHILALI MM, GLEAVE M, FRADET Y: Placebo-associated remissions in a multicentre, randomized, double-blind trial of interferon gamma-lb for the treatment of metastatic renal cell carcinoma. The Canadian Urologic Oncology Group. Br. J. Urol. hat. (2000) 86:613–618.
  • SCHWAAB T, HEANEY JA, SCHNED AR: A randomized Phase II trial comparing two different sequence combinations of autologous vaccine and human recombinant interferon gamma and human recombinant interferon alpha2B therapy in patients with metastatic renal cell carcinoma: clinical outcome and analysis of immunological parameters. J. Um]. (2000) 163:1322–1327.
  • TATE J, OLENCKI T, FINKE J: Phase I trial of simultaneously administered GM-CSF and IL-6 in patients with renal-cell carcinoma: clinical and laboratory effects. Ann. Oncol (2001) 12:655–659.
  • WIGGINTON JM, KOMSCHLIES KL, BACK TC: Administration of interleukin 12 with pulse interleukin 2 and the rapid and complete eradication of murine renal carcinoma. Natl. Cancer Last (1996) 88:38–43.
  • DUDLEY ME, WUNDERLICH JR, ROBBINS PF et al.: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science (2002) 298(5594):850–854.
  • CHANG AE, LI Q, JIANG G, SAYRE DM, BRAUN TM, REDMAN BG. Phase II trial of autologous tumor vaccination, anti-CD3-activated vaccine-primed lymphocytes, and interleukin-2 in stage IV renal cell cancer. Clin. Onc. (2003) 21(5):884–890.
  • FIGLIN RA, PIERCE WC, KABOO R et al.: Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. Ural. (1997) 158(3, Part 1):740–745.
  • ROSENBERG SA, LOTZE MT, YANG JC et al.: Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. Nati Cancer Inst. (1993) 85(8):622–632.
  • RINI BI, ZIMMERMAN T, STADLER WM, GAJEWSKI TF, VOGELZANG NJ: Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results. .1 Clin. Oncol (2002) 20(8):2017–2024.
  • CHILDS R, CHERNOFF A, CONTENTIN N et al.: Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl. J. Med. (2000) 343(11):750–758.
  • ••The original series for RCC allogeneic transplant. Ongoing accrual to newer series will continue to refine the technique.
  • PARDOLL1DM: Cancer vaccines. Nat. Med. (1998) 4(5, Suppl.):525–531.
  • STEINMAN RM, DHODAPKAR M: Active immunization against cancer with dendritic cells: the near future. Int. Cancer (2001) 94(4):459–473.
  • SIMONS JW, JAFFEE EM, WEBER CE et al.: Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. Cancer Res. (1997) 57(8):1537–1546.
  • MACH N, DRANOFF G: Cytokine-secreting tumor cell vaccines. Carr. Opin. brununol (2000) 12(5):571–575.
  • ANTONIA SJ, SEIGNE J, DIAZ Jet al.: Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma.' Ural. (2002) 167(5).
  • SCHWARTZ RH: Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell (1992) 71(7):1065–1068.
  • OVERWIJK WW, THEORET MR, RESTIFO NP: The future of interleukin-2: enhancing therapeutic anticancer vaccines. Cancer" Sci. Am. (2000) 6\(Suppl. 1):576–580.
  • SHIMIZU K: Potentiation of immunologic responsiveness to dendritic cell-based tumor vaccines by recombinant intreleukin-2. Cancer" Sci. Am. (2000) 6\(Suppl. 1):567–575.
  • MARTEN A, FLIEGER D, RENOTH S et al.: Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical Phase I/II trial. Cancer Innnunol. Immunother: (2002) 51(11-12):637–644.
  • HOLTL L, ZELLE-REISER C, GANDER H et al.: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin. Cancer Res. (2002) 8(11):3369–3376.
  • KUGLER A, STUHLER G, WALDEN P et al.: Regression of human metastic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat. Med. (2000) 6(3):332–336.
  • HEISER A, MAURICE MA, YANCEY DR, COLEMAN DM, DAHM P, VIEWEG J: Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors. Cancer Res. (2001) 61(8):3388–3393.
  • Cancer vaccine - Antigenics. BioDrugs (2002) 16(1):72–74.

Websites

  • http://www.ncbi.nlm.nih.gov/ National Center for Biotechnology Information (NCBI) website. Entries for 'NP_001207', 'Q16790', 'CAB82444'(search on `G250').
  • http://www.dkfz-heidelberg.de/abt0840/ whuber/rcc BOER JM, WOLFGANG H, HOLGER S et al.: Identification and classification of differentially expressed genes in renal cell carcinoma by expression profiling on a global human 31,500 element cDNA array.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.