Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

被引:39
作者
Curti, Brendan [1 ]
Crittenden, Marka [1 ,2 ]
Seung, Steven K. [2 ]
Fountain, Christopher B. [3 ]
Payne, Roxanne [3 ]
Chang, ShuChing [4 ]
Fleser, Jessica [3 ]
Phillips, Kimberly [3 ]
Malkasian, Ian [3 ]
Dobrunick, Lyn B. [3 ]
Urba, Walter J. [1 ]
机构
[1] Providence Portland Med Ctr, Providence Canc Inst, Earle A Chiles Res Inst, Portland, OR 97213 USA
[2] Oregon Clin, Div Radiat Oncol, Portland, OR USA
[3] Providence Portland Med Ctr, Providence Canc Inst, Portland, OR USA
[4] Providence St Joseph Hlth, Med Data Res Ctr, Portland, OR USA
关键词
LONG-TERM SURVIVAL; RECOMBINANT INTERLEUKIN-2; RADIATION-THERAPY; TUMOR; EXPRESSION; CELLS; IRRADIATION; GUIDELINES; NIVOLUMAB; IMMUNITY;
D O I
10.1136/jitc-2020-000773
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. Methods Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. Results 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression--free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). Conclusions SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL- 2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses.
引用
收藏
页数:10
相关论文
共 28 条
[1]   Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma [J].
Alva, Ajjai ;
Daniels, Gregory A. ;
Wong, Michael K. K. ;
Kaufman, Howard L. ;
Morse, Michael A. ;
McDermott, David F. ;
Clark, Joseph I. ;
Agarwala, Sanjiv S. ;
Miletello, Gerald ;
Logan, Theodore F. ;
Hauke, Ralph J. ;
Curti, Brendan ;
Kirkwood, John M. ;
Gonzalez, Rene ;
Amin, Asim ;
Fishman, Mayer ;
Agarwal, Neeraj ;
Lowder, James N. ;
Hua, Hong ;
Aung, Sandra ;
Dutcher, Janice P. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2016, 65 (12) :1533-1544
[2]   High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993 [J].
Atkins, MB ;
Lotze, MT ;
Dutcher, JP ;
Fisher, RI ;
Weiss, G ;
Margolin, K ;
Abrams, J ;
Sznol, M ;
Parkinson, D ;
Hawkins, M ;
Paradise, C ;
Kunkel, L ;
Rosenberg, SA .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (07) :2105-2116
[3]  
Atkins MB, 2000, CANCER J SCI AM, V6, pS11
[4]   Stimulating Innate Immunity to Enhance Radiation Therapy-Induced Tumor Control [J].
Baird, Jason R. ;
Monjazeb, Arta M. ;
Shah, Omid ;
McGee, Heather ;
Murphy, William J. ;
Crittenden, Marka R. ;
Gough, Michael J. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2017, 99 (02) :362-373
[5]   Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy [J].
Chakraborty, M ;
Abrams, SI ;
Camphausen, K ;
Liu, KB ;
Scott, T ;
Coleman, CN ;
Hodge, JW .
JOURNAL OF IMMUNOLOGY, 2003, 170 (12) :6338-6347
[6]   High-dose interleukin-2 (HD IL-2) for advanced melanoma: a single center experience from the University of Pittsburgh Cancer Institute [J].
Davar, Diwakar ;
Ding, Fei ;
Saul, Melissa ;
Sander, Cindy ;
Tarhini, Ahmad A. ;
Kirkwood, John M. ;
Tawbi, Hussein A. .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2017, 5
[7]   Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated [J].
Demaria, S ;
Ng, B ;
Devitt, ML ;
Babb, JS ;
Kawashima, N ;
Liebes, L ;
Formenti, SC .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2004, 58 (03) :862-870
[8]   STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors [J].
Deng, Liufu ;
Liang, Hua ;
Xu, Meng ;
Yang, Xuanming ;
Burnette, Byron ;
Arina, Ainhoa ;
Li, Xiao-Dong ;
Mauceri, Helena ;
Beckett, Michael ;
Darga, Thomas ;
Huang, Xiaona ;
Gajewski, Thomas F. ;
Chen, Zhijian J. ;
Fu, Yang-Xin ;
Weichselbaum, Ralph R. .
IMMUNITY, 2014, 41 (05) :843-852
[9]   Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies [J].
Dobry, Allison S. ;
Zogg, Cheryl K. ;
Hodi, F. Stephen ;
Smith, Timothy R. ;
Ott, Patrick A. ;
Iorgulescu, J. Bryan .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2018, 67 (12) :1833-1844
[10]   INCREASED TUMOR NECROSIS FACTOR-ALPHA MESSENGER-RNA AFTER CELLULAR EXPOSURE TO IONIZING-RADIATION [J].
HALLAHAN, DE ;
SPRIGGS, DR ;
BECKETT, MA ;
KUFE, DW ;
WEICHSELBAUM, RR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) :10104-10107