Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma

Ann Oncol. 2009 Jul;20(7):1275-9. doi: 10.1093/annonc/mdn775. Epub 2009 Feb 26.

Abstract

Background: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of approximately 30% and median survival of 6 months.

Patients and methods: In a multicentre phase II study, 32 patients with recurrent or metastatic HNSCC received 3-AP Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), an inhibitor of ribonucleotide reductase, 96 mg/m2, daily for 4 days every 14 days (one cycle). Eligibility criteria required Eastern Cooperative Oncology Group performance status (ECOG PS) of zero to two with a life expectancy of >3 months; one prior chemotherapy regimen was allowed.

Results: Thirty patients were assessable for response and toxicity. Median age was 57 years (range 36-79) and median ECOG PS was one (range 0-2). Thirteen patients had previously been treated with chemotherapy. A total of 130 cycles were administered with a median number of cycles of 3.5 (range 1-8). Mild anaemia (40%), nausea (22%) and fatigue (22%) were commonly reported with G3 and G4 neutropenia documented in 22% and 22%, respectively. Overall response rate was 5.9% (95% confidence interval 0.2% to 28.7%). One patient achieved a partial response, eight had stable disease and 21 progressive disease. Median time to disease progression was 3.9 months.

Conclusions: 3-AP Triapine as a single agent, at this dose and schedule, is well tolerated but has only minor activity in the treatment of advanced HNSCC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Drug Administration Schedule
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Recurrence, Local / drug therapy
  • Pyridines / administration & dosage*
  • Thiosemicarbazones / administration & dosage*

Substances

  • Antineoplastic Agents
  • Pyridines
  • Thiosemicarbazones
  • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone