A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma

Julie E. Bauman, Hugo Arias-Pulido, Sang Joon Lee, M. Houman Fekrazad, Hiroyuki Ozawa, Elana Fertig, Jason Howard, Justin Bishop, Hao Wang, Garth T. Olson, Michael J. Spafford, Dennie V. Jones, Christine H. Chung

Research output: Contribution to journalArticle

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Abstract

Objectives: The epidermal growth factor receptor (EGFR) is a validated target in head and neck squamous cell carcinoma (HNSCC). In recurrent and/or metastatic (R/M) HNSCC, resistance to anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/Akt/mTOR pathway is an established resistance mechanism. Concurrent mTOR blockade may improve efficacy of anti-EGFR therapy. Materials and methods: Erlotinib 150 mg daily and temsirolimus 15 mg weekly were administered to patients with platinum-refractory R/M HNSCC and ECOG performance status 0-2. The primary endpoint was progression-free survival (PFS). Correlative studies determined PIK3CA and HRAS mutation status; p16, EGFR, pS6K, pAkt and PTEN expression; and pre- and post-treatment plasma levels of 20 immunomodulatory cytokines. Results: Twelve patients enrolled; six withdrew within 6 weeks due to toxicity or death, prompting early closure of the trial. Grade ≥ 3 toxicities included fatigue, diarrhea, gastrostomy tube infection, peritonitis, pneumonia, dyspnea, and HN edema. Median PFS was 1.9 months. Median overall survival was 4.0 months. Six/12 tumors were p16(+), 9/11 lacked measurable PTEN expression, and 1/12 harbored a PIK3CA mutation. On exploratory analysis, high baseline plasma VEGF and interferon-gamma levels marginally associated with tumor progression. Conclusions: The combination of erlotinib and temsirolimus was poorly tolerated. Low prevalence of PTEN expression and 8% incidence of PIK3CA mutations indicate biological relevance of this pathway in R/M disease. Investigation of more tolerable combinations of EGFR and PI3K/Akt/mTOR pathway inhibitors in selected HNSCC patients is warranted.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalOral Oncology
Volume49
Issue number5
DOIs
StatePublished - May 1 2013

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Platinum
Epidermal Growth Factor Receptor
Phosphatidylinositol 3-Kinases
Mutation
Disease-Free Survival
Gastrostomy
Therapeutics
Peritonitis
Dyspnea
Vascular Endothelial Growth Factor A
Interferon-gamma
Fatigue
Diarrhea
Edema
Neoplasms
Pneumonia
Carcinoma, squamous cell of head and neck
temsirolimus
Erlotinib Hydrochloride
Cytokines

Keywords

  • EGFR
  • Erlotinib
  • Head and neck squamous cell carcinoma
  • mTOR
  • PIK3CA
  • Platinum-refractory
  • Temsirolimus

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. / Bauman, Julie E.; Arias-Pulido, Hugo; Lee, Sang Joon; Fekrazad, M. Houman; Ozawa, Hiroyuki; Fertig, Elana; Howard, Jason; Bishop, Justin; Wang, Hao; Olson, Garth T.; Spafford, Michael J.; Jones, Dennie V.; Chung, Christine H.

In: Oral Oncology, Vol. 49, No. 5, 01.05.2013, p. 461-467.

Research output: Contribution to journalArticle

Bauman, JE, Arias-Pulido, H, Lee, SJ, Fekrazad, MH, Ozawa, H, Fertig, E, Howard, J, Bishop, J, Wang, H, Olson, GT, Spafford, MJ, Jones, DV & Chung, CH 2013, 'A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma', Oral Oncology, vol. 49, no. 5, pp. 461-467. https://doi.org/10.1016/j.oraloncology.2012.12.016
Bauman, Julie E. ; Arias-Pulido, Hugo ; Lee, Sang Joon ; Fekrazad, M. Houman ; Ozawa, Hiroyuki ; Fertig, Elana ; Howard, Jason ; Bishop, Justin ; Wang, Hao ; Olson, Garth T. ; Spafford, Michael J. ; Jones, Dennie V. ; Chung, Christine H. / A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. In: Oral Oncology. 2013 ; Vol. 49, No. 5. pp. 461-467.
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AU - Arias-Pulido, Hugo

AU - Lee, Sang Joon

AU - Fekrazad, M. Houman

AU - Ozawa, Hiroyuki

AU - Fertig, Elana

AU - Howard, Jason

AU - Bishop, Justin

AU - Wang, Hao

AU - Olson, Garth T.

AU - Spafford, Michael J.

AU - Jones, Dennie V.

AU - Chung, Christine H.

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