Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy

Cancer. 2011 Oct 15;117(20):4617-22. doi: 10.1002/cncr.26124. Epub 2011 Mar 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / analysis
  • Capecitabine
  • Carcinoma, Neuroendocrine / chemistry
  • Carcinoma, Neuroendocrine / drug therapy*
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / pathology*
  • Cisplatin / administration & dosage
  • DNA Methylation / genetics*
  • DNA Modification Methylases / genetics*
  • DNA Repair / genetics*
  • DNA Repair Enzymes / genetics*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Salvage Therapy / methods
  • Temozolomide
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • Bevacizumab
  • Capecitabine
  • Etoposide
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Cisplatin
  • Fluorouracil
  • Temozolomide