Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma

被引:44
作者
Jonasch, Eric [1 ]
Stadler, Walter M. [2 ]
Bukowski, Ronald M. [3 ]
Hayes, Teresa G. [4 ]
Varadhachary, Atul [5 ]
Malik, Rajesh [5 ]
Figlin, Robert A. [6 ]
Srinivas, Sandy [7 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Oncol, Houston, TX 77030 USA
[2] Univ Chicago, Med Ctr, Dept Clin Res, Chicago, IL 60637 USA
[3] Case Western Reserve Univ, Dept Med, CCF Taussig Canc Ctr, CCF Lerner Coll Med, Cleveland, OH 44106 USA
[4] Vet Affairs Med Ctr, Dept Hematol Oncol, Houston, TX 77030 USA
[5] Agennix Inc, Houston, TX USA
[6] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA
[7] Stanford Univ, Dept Med Oncol, Stanford, CA 94305 USA
关键词
renal cell carcinoma; talactoferrin; clinical antitumor activity; phase; 2; trial; survival;
D O I
10.1002/cncr.23519
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron-binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine-activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types. The purpose of the current study was to evaluate the activity and safety of TLF in patients with refractory metastatic renal cell carcinoma (RCC). METHODS. Forty-four adult patients with progressive advanced or metastatic RCC who had failed prior systemic therapy received oral talactoferrin at a dose of 1.5 g twice daily on a 12-week-on 2-week-off schedule. Patients were evaluated for progression-free survival at 14 weeks, overall response rate, and progression-free and overall survival. RESULTS. TLF was well tolerated. No significant hematologic, hepatic, or renal toxicities were reported. The study met its predefined target with a 14-week progression-free survival rate of 59%. The response rate was 4.5%. The mMedian progression-free survival was 6.4 months and the median overall survival was 21.1 months. CONCLUSIONS. TLF is a well-tolerated new agent that has demonstrated preliminary signs of clinical activity. Given the lack of toxicity, the lack of rapid disease progression in this cohort, and the preclinical data on immune activation, a randomized study assessing its effects on disease progression in patients with metastatic RCC is rational.
引用
收藏
页码:72 / 77
页数:6
相关论文
共 25 条
  • [1] ANTIBACTERIAL SPECTRUM OF LACTOFERRICIN-B, A POTENT BACTERICIDAL PEPTIDE DERIVED FROM THE N-TERMINAL REGION OF BOVINE LACTOFERRIN
    BELLAMY, W
    TAKASE, M
    WAKABAYASHI, H
    KAWASE, K
    TOMITA, M
    [J]. JOURNAL OF APPLIED BACTERIOLOGY, 1992, 73 (06): : 472 - 479
  • [2] Sorafenib in advanced clear-cell renal-cell carcinoma
    Escudier, Bernard
    Eisen, Tim
    Stadler, Walter M.
    Szczylik, Cezary
    Oudard, Stephane
    Siebels, Michael
    Negrier, Sylvie
    Chevreau, Christine
    Solska, Ewa
    Desai, Apurva A.
    Rolland, Frederic
    Demkow, Tomasz
    Hutson, Thomas E.
    Gore, Martin
    Freeman, Scott
    Schwartz, Brian
    Shan, Minghua
    Simantov, Ronit
    Bukowski, Ronald M.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) : 125 - 134
  • [3] INFLUENCE OF LACTOFERRIN ON THE FUNCTION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND MONOCYTES
    GAHR, M
    SPEER, CP
    DAMERAU, B
    SAWATZKI, G
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1991, 49 (05) : 427 - 433
  • [4] Phase I trial of oral talactoferrin alfa in refractory solid tumors
    Hayes, TG
    Falchook, GF
    Varadhachary, GR
    Smith, DP
    Davis, LD
    Dhingra, HM
    Hayes, BP
    Varadhachary, A
    [J]. INVESTIGATIONAL NEW DRUGS, 2006, 24 (03) : 233 - 240
  • [5] Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma
    Hudes, Gary
    Carducci, Michael
    Tomczak, Piotr
    Dutcher, Janice
    Figlin, Robert
    Kapoor, Anil
    Staroslawska, Elzbieta
    Sosman, Jeffrey
    McDermott, David
    Bodrogi, Istvan
    Kovacevic, Zoran
    Lesovoy, Vladimir
    Schmidt-Wolf, Ingo G. H.
    Barbarash, Olga
    Gokmen, Erhan
    O'Toole, Timothy
    Lustgarten, Stephanie
    Moore, Laurence
    Motzer, Robert J.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (22) : 2271 - 2281
  • [6] Cancer statistics, 2007
    Jemal, Ahmedin
    Siegel, Rebecca
    Ward, Elizabeth
    Murray, Taylor
    Xu, Jiaquan
    Thun, Michael J.
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) : 43 - 66
  • [7] Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial
    Jocham, D
    Richter, A
    Hoffmann, L
    Iwig, K
    Fahlenkamp, D
    Zakrzewski, G
    Schmitt, E
    Dannenberg, T
    Lehmacher, W
    von Wietersheim, J
    Doehn, C
    [J]. LANCET, 2004, 363 (9409) : 594 - 599
  • [8] Lactoferrin and its biological functions
    Kanyshkova, TG
    Buneva, VN
    Nevinsky, GA
    [J]. BIOCHEMISTRY-MOSCOW, 2001, 66 (01) : 1 - 7
  • [9] Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma
    McDermott, DF
    Regan, MM
    Clark, JI
    Flaherty, LE
    Weiss, GR
    Logan, TF
    Kirkwood, JM
    Gordon, MS
    Sosman, JA
    Ernstoff, MS
    Tretter, CPG
    Urba, WJ
    Smith, JW
    Margolin, KA
    Mier, JW
    Gollob, JA
    Dutcher, JP
    Atkins, MB
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (01) : 133 - 141
  • [10] Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma
    Motzer, RJ
    Bacik, J
    Murphy, BA
    Russo, P
    Mazumdar, M
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (01) : 289 - 296