A phase I/II study of lenalidomide in combination with sunitinib in patients with advanced or metastatic renal cell carcinoma

被引:9
|
作者
Rini, B. [1 ]
Redman, B. [2 ]
Garcia, J. A. [1 ]
Burris, H. A., III [3 ]
Li, S. [4 ]
Fandi, A. [4 ]
Beck, R. [4 ]
Jungnelius, U. [4 ]
Infante, J. R. [3 ]
机构
[1] Glickman Urol Inst, Cleveland Clin Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44195 USA
[2] Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA
[3] Sarah Cannon Res Inst Tennessee Oncol PLLC, Nashville, TN USA
[4] Celgene Corp, Summit, NJ USA
关键词
sunitinib; lenalidomide; metastatic renal cell carcinoma; phase I/II; maximum tolerated dose; TRIAL; THERAPY; GROWTH; CANCER; AGENTS;
D O I
10.1093/annonc/mdu212
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide plus sunitinib in metastatic renal cell carcinoma (RCC) patients. Patients and methods: Patients with histologically confirmed, metastatic RCC were treated with 10 mg/day lenalidomide plus 37.5 mg/day sunitinib, orally in 21-day cycles. Doses were escalated to determine the MTD in phase I, with additional patients planned at this dose in phase II. Primary end points were MTD and response rate. Results: Sixteen patients received a median of 2, 3, and 5 cycles in cohort 1 [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-21)], cohort 2 [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], and cohort 3 [lenalidomide 15 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], respectively. Median treatment durations were 41, 63, and 97 days for lenalidomide; and 41, 57, and 97.5 days for sunitinib. The MTD was found to be continuous dosing of lenalidomide 10 mg/day plus sunitinib 37.5 mg/day for 14 of 21 days. Dose-limiting toxicities included neutropenia, leukopenia, thrombocytopenia, asthenia, atrial fibrillation, and increased transaminases. The most frequent grade 3-4 treatment-emergent adverse events were hematologic, including neutropenia and leukopenia. One patient achieved partial response, and seven had stable disease of which three were confirmed at subsequent tumor assessments. B cells and several T-cell subsets were modulated versus baseline. Conclusion: The dose schedules of lenalidomide and sunitinib evaluated in this study were not well tolerated; cumulative toxicity precluded enrollment at the MTD.
引用
收藏
页码:1794 / 1799
页数:7
相关论文
共 50 条
  • [41] Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer
    Di Lorenzo, Giuseppe
    Carteni, Giacomo
    Autorino, Riccardo
    Bruni, Gianni
    Tudini, Marianna
    Rizzo, Mimma
    Aieta, Michele
    Gonnella, Antonio
    Rescigno, Pasquale
    Perdona, Sisto
    Giannarini, Gianluca
    Pignata, Sandro
    Longo, Nicola
    Palmieri, Giovannella
    Imbimbo, Ciro
    De Laurentiis, Michele
    Mirone, Vincenzo
    Ficorella, Corrado
    De Placido, Sabino
    JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (27) : 4469 - 4474
  • [42] Sunitinib rechallenge in advanced renal cell carcinoma: outcomes of a multicenter retrospective study
    Munarriz, Javier
    Reynes, Gaspar
    Sanchez-Lorenzo, Luisa
    Esteban, Emilio
    Basterretxea, Laura
    de Avila-Lizarraga, Leticia
    Angel Climent, Miguel
    Jose Juan-Fita, Maria
    Escoin, Corina
    Puente, Javier
    Cassinello, Javier
    Vazquez, Sergio
    Chirivella, Isabel
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2019, 84 (04) : 781 - 789
  • [43] Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma: A Randomized Phase 2 Study
    Lindskog, Magnus
    Laurell, Anna
    Kjellman, Anders
    Melichar, Bohuslav
    Rey, Pablo Maroto
    Zielinski, Henryk
    Villacampa, Felipe
    Bigot, Pierre
    Zoltan, Bajory
    Parikh, Omi
    Alba, David Vazquez
    Jellvert, Dsa
    Flasko, Tibor
    Gallardo, Enrique
    Caparros, Maria Jose Ribal
    Purkalne, Gunta
    Suenaert, Peter
    Karlsson-Parra, Alex
    Ljungberg, Borje
    EUROPEAN UROLOGY OPEN SCIENCE, 2022, 40 : 38 - 45
  • [44] A Phase II Study of Bevacizumab and Everolimus as Treatment for Refractory Metastatic Renal Cell Carcinoma
    Harshman, Lauren C.
    Barbeau, Sarah
    McMillian, Alex
    Srinivas, Sandy
    CLINICAL GENITOURINARY CANCER, 2013, 11 (02) : 100 - 106
  • [45] Metformin Use and Outcome of Sunitinib Treatment in Patients With Diabetes and Metastatic Renal Cell Carcinoma
    Keizman, Daniel
    Ish-Shalom, Maya
    Sella, Avishay
    Gottfried, Maya
    Maimon, Natalie
    Peer, Avivit
    Hammers, Hans
    Eisenberger, Mario A.
    Sinibaldi, Victoria
    Neiman, Victoria
    Rosenbaum, Eli
    Sarid, David
    Mermershtain, Wilmosh
    Rouvinov, Keren
    Berger, Raanan
    Carducci, Michael A.
    CLINICAL GENITOURINARY CANCER, 2016, 14 (05) : 420 - 425
  • [46] Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma
    Voss, Martin H.
    Chen, David
    Marker, Mahtab
    Hakimi, A. Ari
    Lee, Chung-Han
    Hsieh, James J.
    Knox, Jennifer J.
    Voi, Maurizio
    Motzer, Robert J.
    BRITISH JOURNAL OF CANCER, 2016, 114 (06) : 642 - 649
  • [47] Phase II Trial of Pemetrexed Plus Gemcitabine in Patients With Locally Advanced and Metastatic Nonclear Cell Renal Cell Carcinoma
    Richey, Stephen L.
    Tamboli, Pheroze
    Ng, Chaan S.
    Lin, E.
    Lim, Zita D.
    Araujo, John C.
    Jonasch, Eric
    Sharma, Padmanee
    Pagliaro, Lance C.
    Tannir, Nizar M.
    AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2013, 36 (05): : 450 - 454
  • [48] Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study
    Atkins, Michael B.
    Gravis, Gwenaelle
    Drosik, Kazimierz
    Demkow, Tomasz
    Tomczak, Piotr
    Wong, Shirley S.
    Michaelson, M. Dror
    Choueiri, Toni K.
    Wu, Benjamin
    Navale, Lynn
    Warner, Douglas
    Ravaud, Alain
    JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (30) : 3431 - +
  • [49] Sequential therapies with sorafenib and sunitinib in advanced or metastatic renal cell carcinoma
    Herrmann, E.
    Marschner, N.
    Grimm, M. O.
    Ohlmann, C. H.
    Hutzschenreuter, U.
    Overkamp, F.
    Groschek, M.
    Blumenstengel, K.
    Puehse, G.
    Steiner, T.
    WORLD JOURNAL OF UROLOGY, 2011, 29 (03) : 361 - 366
  • [50] Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma
    Lee, J. -L.
    Ahn, J. -H.
    Lim, H. Y.
    Park, S. H.
    Lee, S. H.
    Kim, T. M.
    Lee, D. -H.
    Cho, Y. M.
    Song, C.
    Hong, J. H.
    Kim, C. -S.
    Ahn, H.
    ANNALS OF ONCOLOGY, 2012, 23 (08) : 2108 - 2114