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Oncotarget. 2015 Oct 6;6(30):29808-17. doi: 10.18632/oncotarget.5060.

Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients.

Author information

1
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
2
Institue of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsinchu, Taiwan.
3
Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
4
School of Medicine and Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.

Abstract

RATIONALE:

According to the metabolic symbiosis model, cancer stromal fibroblasts could be hijacked by surrounding cancer cells into a state of autophagy with aerobic glycolysis to help provide recycled nutrients. The purpose of this study was to investigate whether combined treatment with the autophagy inhibitor: hydroxychloroquine (HCQ) and the autophagy inducer: sirolimus (rapamycin, Rapa) would reduce glucose utilization in sarcoma patients.

METHODS:

Ten sarcoma patients who failed first-line treatment were enrolled in this study. They were treated with 1 mg of Rapa and 200 mg of HCQ twice daily for two weeks. The standardized uptake values (SUV) from pretreatment and posttreatment [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) scans were reviewed, and changes from the baseline SUVmax were evaluated.

RESULTS:

Based on FDG PET response criteria, six patients had a partial response; three had stable disease, and one had progressive disease. Nevertheless, none of them showed a reduction in tumor volume. The mean SUVmax reduction in the 34 lesions evaluated was - 19.6% (95% CI = -30.1% to -9.1%), while the mean volume change was +16.4% (95% CI = +5.8% to + 27%). Only grade 1 toxicities were observed. Elevated serum levels of lactate dehydrogenase were detected after treatment in most metabolic responders.

CONCLUSIONS:

The results of reduced SUVmax without tumor volume reduction after two weeks of Rapa and HCQ treatment may indicate that non-proliferative glycolysis occurred mainly in the cancer associated fibroblast compartment, and decreased glycolytic activity was evident from Rapa + HCQ double autophagy modulator treatment.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01842594.

KEYWORDS:

hydroxychloroquine; sirolimus; soft tissue sarcoma

PMID:
26375670
PMCID:
PMC4745764
DOI:
10.18632/oncotarget.5060
[Indexed for MEDLINE]
Free PMC Article

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