title: Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy.
abstract: BACKGROUND
  Patients with metastatic poorly differentiated endocrine carcinoma (PDEC) usually have a short survival. The chemotherapy combination of cisplatin and etoposide is frequently used as first-line palliative chemotherapy. There are, however, no published studies concerning second-line treatment of the disease. Temozolomide has shown clinical effect in well-differentiated endocrine carcinomas. This study was performed to evaluate the effect of temozolomide in PDEC patients who had progressed on first-line treatment.
  
  
  METHODS
  Twenty-five patients with PDEC (mainly gastrointestinal) were treated with temozolomide alone or in combination with capecitabine. A subset of patient also received bevacizumab. MGMT methylation was analyzed in tissue specimens. Data were collected retrospectively.
  
  
  RESULTS
  One patient had a complete response, and 7 patients had partial response (33% response rate). Median duration of response was 19 months. Another 9 (38%) patients had a stable disease, after progression at inclusion, with a median duration of 18 months. Median progression-free survival for all patients was 6 months, and median overall survival was 22 months. Only 1 patient had a MGMT methylation.
  
  
  CONCLUSIONS
  Treatment with temozolomide alone or in combination with capecitabine and bevacizumab resulted in objective response or stabilization in 71% of PDEC patients who failed on first-line chemotherapy. These results indicated that temozolomide may be used as second-line treatment in PDEC.
authors: Department of Medical Sciences, Endocrine Oncology, Uppsala University, Sweden. Staffan.welin@medsci.uu.se
authors: Staffan
authors: S
authors: Welin
authors: Halfdan
authors: H
authors: Sorbye
authors: Sigrunn
authors: S
authors: Sebjornsen
authors: Stian
authors: S
authors: Knappskog
authors: Christian
authors: C
authors: Busch
authors: Kjell
authors: K
authors: Oberg
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis; D000069287:Capecitabine; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005047:Etoposide; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D002945:Cisplatin; D005472:Fluorouracil; D000077204:Temozolomide