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

• Published in: Annals of oncology Vol. 20; no. 7; pp. 1275 - 1279
• Main Authors: Nutting, C.M., van Herpen, C.M.L., Miah, A.B., Bhide, S.A., Machiels, J.-P., Buter, J., Kelly, C., de Raucourt, D., Harrington, K.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2009; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: 3-AP Triapine; Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; chemotherapy; Drug Administration Schedule; Female; head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Neoplasm Metastasis - drug therapy; Neoplasm Recurrence, Local - drug therapy; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Pyridines - administration & dosage; Thiosemicarbazones - administration & dosage; Tumors; head and neck cancer; 3-AP Triapine; chemotherapy; Human; Relapse; Patient; Malignant tumor; Metastasis; Chemotherapy; Treatment; Phase II trial; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; Advanced stage; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdn775

Background: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of ∼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.