Phase II study of sorafenib in combination with cisplatin and 5-fluorouracil to treat recurrent or metastatic nasopharyngeal carcinoma

Ann Oncol. 2013 Apr;24(4):1055-61. doi: 10.1093/annonc/mds581. Epub 2012 Nov 21.

Abstract

Background: We aimed to investigate the efficacy and tolerability of sorafenib combined with cisplatin and 5-fluorouracil (5-FU) in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).

Patients and methods: It was a Simon two-stage designed trial. Chemotherapy-naive patients with recurrent or metastatic disease were enrolled. The regimen was sorafenib 400 mg orally b.i.d., cisplatin 80 mg/m(2) i.v. day 1, and 5-FU 1000 mg/m(2)/day CIV for 4 days, repeated every 21 days. After a maximum of six cycles of chemotherapy, patients received maintenance of sorafenib.

Results: In total, 54 patients were enrolled. The objective response rate reached 77.8%, including 1 complete response and 41 partial responses. The median progression-free survival was 7.2 months (95% CI 6.8-8.4 months), and the median overall survival was 11.8 months (95% CI 10.6-18.7 months). Major toxic effects included hand-foot skin reaction, myelosuppression, and gastrointestinal (GI) reaction. The incidence of hemorrhage was 22.2%, and one patient with liver metastases died of GI bleeding. Contrast-enhanced ultrasonography was carried out in a subset of patients with liver metastases.

Conclusion: Combination of sorafenib, cisplatin (80 mg/m(2)) and 5-FU (3000 mg/m(2)) was tolerable and feasible in recurrent or metastatic NPC. Further randomized trials to compare sorafenib plus cisplatin and 5-FU with standard dose of cisplatin plus 5-FU in NPC are warranted.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Drug-Related Side Effects and Adverse Reactions / chemically induced
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / adverse effects
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local / pathology
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Sorafenib
  • Ultrasonography

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • Cisplatin
  • Fluorouracil