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Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT).

Methods

In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT.

Results

Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by 68Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using 177Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months.

Conclusion

Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC.

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Acknowledgments

D. Neil Watkins and Rodney J. Hicks received financial support from the Victorian Cancer Agency.

Conflicts of interest

None.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, East Melbourne, VIC, Australia

    Jeremy Lewin, Aparna Rao & Linda Mileshkin

  2. Division of Cancer Research, East Melbourne, VIC, Australia

    Carleen Cullinane & Kelly Waldeck

  3. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Place, Locked Bag No. 1, A’Beckett St, East Melbourne, VIC, 8006, Australia

    Tim Akhurst, Peter Eu & Rodney J. Hicks

  4. Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia

    D. Neil Watkins

  5. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Melbourne, VIC, Australia

    Carleen Cullinane & Rodney J. Hicks

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  1. Jeremy Lewin
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Corresponding author

Correspondence to Rodney J. Hicks.

Additional information

Jeremy Lewin and Carleen Cullinane contributed equally to the results presented in this report.

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Lewin, J., Cullinane, C., Akhurst, T. et al. Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside. Eur J Nucl Med Mol Imaging 42, 25–32 (2015). https://doi.org/10.1007/s00259-014-2888-2

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  • DOI: https://doi.org/10.1007/s00259-014-2888-2

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