Toxicities, safeties and clinical response of dacarbazine-based chemotherapy on neuroendocrine tumors in Taiwan population

J Chin Med Assoc. 2018 May;81(5):423-428. doi: 10.1016/j.jcma.2017.08.020. Epub 2017 Dec 26.

Abstract

Background: Currently, the role of dacarbazine (DTIC) based chemotherapy in neuroendocrine tumors (NETs) in Asia is unclear. Here, we report the outcomes of dacarbazine (DTIC)-based chemotherapy in Taiwan population.

Methods: DTIC alone (250 mg/m2/day), or 5-fluorouracil (5-FU, 500 mg/m2/day) and DTIC (200 mg/m2/day) with or without epirubicin (200 mg/m2/day), for 3 days, every 3-4 weeks. Subgroups were analyzed by grading, and by Ki-67 index.

Results: 48 patients were reviewed in this study, including 3 had grade 1 tumors, 23 had grade 2, while 22 were grade 3. In grade 3 NEC patients, the tumor Ki-67 index of 21-55% were noted in 8 patients, and >55% in 14 patients. Progression-free survival (PFS) was 5.1 months, and overall survival (OS) was 31.6 months. The PFS (in months) were 12.5 and 1.8 for patients with NETs and neuroendocrine carcinomas (NECs), respectively (p < 0.001). The OS were not reached and 5.9 months for patients with NETs and NECs, respectively (p = 0.001). Patients with NECs were divided into two groups, according to their Ki-67 index. In patients with a tumor Ki-67 index of 21-55%, PFS was 4.1 months, and OS was not reached; in those with a tumor Ki-67 index of >55%, they were 1.5 and 1.8 months, respectively (p < 0.001 and p = 0.013).

Conclusion: NETs, and grade 3 NECs, with Ki-67 indices of 20-55% had good responses to DTIC-based chemotherapy, with acceptable side effects. Ki-67 index could predict prognosis for grade 3 NEC patients, and guide further chemotherapy choices.

Keywords: Dacarbazine; Ki-67 index; Neuroendocrine carcinoma; Neuroendocrine tumors; Overall survival; Progression-free survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Dacarbazine / adverse effects*
  • Female
  • Humans
  • Ki-67 Antigen
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality

Substances

  • Ki-67 Antigen
  • Dacarbazine