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Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma

  1. Author:
    Reid, Erin G
    Suazo, Adrienne
    Lensing, Shelly Y
    Dittmer, Dirk P [ORCID]
    Ambinder, Richard F
    Maldarelli, Frank
    Gorelick,Robert [ORCID]
    Aboulafia, David M
    Mitsuyasu, Ronald
    Dickson, Mark A
    Wachsman, William

  2. Author Address

    Hematology/Oncology, Moores Cancer Center, University of California, San Diego egreid@ucsd.edu., Hematology/Oncology, Moores Cancer Center, University of California, San Diego., Biostatistics, University of Arkansas for Medical Sciences., Lineberger Comprehensive Cancer Center, UNC Chapel Hill., Oncology, Johns Hopkins University School of Medicine., HIV Drug Resistance Program, National Cancer Institute., Frederick National Laboratory for Cancer Research, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research., Floyd and Delores Jones Cancer Institute, Virginia Mason Medical Center., UCLA CARE Center, University of California, Los Angeles, Center for AIDS Research and Education., Department of Medicine, Memorial Sloan Kettering Cancer Center., Hematology/Oncology, Moores Cancer Center, University of California, San Diego and VA San Diego Healthcare System.,
    1. Year: 2020
    2. Date: FEB
    3. Epub Date: 2019 10 17
  2. Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
    1. 26
    2. 3
    3. Pages: 558-565
  4. Type of Article: Article
  5. ISSN: 1078-0432
  1. Abstract:

    PURPOSE: AIDS-related Kaposi sarcoma (KS) is often incompletely controlled, requiring serial therapies. KS herpesvirus (KSHV) induces transformation of endothelial cells, where it resides in a predominately latent state. We hypothesized proteasome inhibition would have direct anti-tumor activity, induce lytic activation of KSHV, and inhibit HIV infectivity, improving control of both KS and HIV. The primary objective was determining the maximum tolerated dose (MTD) of bortezomib in AIDS-KS. Secondary objectives included estimating the impact of bortezomib on KS response, KSHV plasma DNA copy number (PDCN) and HIV viral loads (VL). METHODS: A 3+3 dose escalation design was employed evaluating 4 dose levels of bortezomib (0.75, 1, 1.2, or 1.6 mg/m2) administered intravenously on days 1, 8, and 15 of 28-day cycles in patients with relapsed/refractory (r/r) AIDS-KS taking antiretroviral therapy. RESULTS: Seventeen patients enrolled. No dose limiting toxicities occurred and the MTD was not reached. The most common adverse events included diarrhea, fatigue and nausea. Among 15 patients evaluable, partial response (PR) occurred in 9 (60%), with PR rate of 83% in the 1.6 mg/m2cohort; the remainder had stable disease (SD). Median time to response was 2.1 months. Median change in KSHV PDCN was significantly different between those with PR versus SD. During cycle 1, 7 of 11 evaluable patients had decreases in HIV VL. CONCLUSION: Bortezomib is well-tolerated and active in AIDS-KS. The 60% PR rate is notable given the dose-finding nature of the study in a r/r population. Changes in KSHV PDCN and HIV VL trended as hypothesized. Copyright ©2019, American Association for Cancer Research.

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External Sources

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  2. DOI: 10.1158/1078-0432.CCR-19-1044
  3. PMID: 31624104
  4. View record in Web of Science®
  5. WOS: 000522788900008
  6. PII : 1078-0432.CCR-19-1044

Library Notes

  1. Fiscal Year: FY2019-2020
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