title: Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside.
abstract: OBJECTIVE
  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 (68)Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using (177)Lu-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.
  
  
  CONCLUSIONS
  Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC.
authors.affiliation: Division of Hematology and Medical Oncology, East Melbourne, VIC, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Lewin
authors.forename: Carleen
authors.initials: C
authors.lastname: Cullinane
authors.forename: Tim
authors.initials: T
authors.lastname: Akhurst
authors.forename: Kelly
authors.initials: K
authors.lastname: Waldeck
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.forename: Aparna
authors.initials: A
authors.lastname: Rao
authors.forename: Peter
authors.initials: P
authors.lastname: Eu
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000628:therapy*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000628:therapy*; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse; C121107:octreotide, DOTA-Tyr(3)-; D005047:Etoposide; C447941:lutetium Lu 177 dotatate; D016190:Carboplatin; D015282:Octreotide