For the treatment of metastatic head and neck cancer, therapeutic options include chemotherapy, with best supportive care for patients unable or unwilling to undergo treatment. Palliative chemotherapy has demonstrated survival advantages over best supportive care, and the most commonly used agents are cisplatin and carboplatin, generally in combination regimens with infusional fluorouracyl or a taxane. The question therefore relates to the addtion of Erbitux to an otherwise standard of care regimen.
There is sginificant body of literature about Taxol, platin drug and cetuximab. In regard to Taxol/platin + cetuximab: A phase II trial evaluating this induction chemotherapy plus cetuximab (Erbitux) resulted in a 100% overall response rate among patients with head and neck cancer. These results were presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO).The trial known as Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME), involved 442 patients. About a third had cancer in the oral cavity or hypopharynx, nearly half had metastases, and most patients had already received treatment with radiotherapy (77% – 80%) and chemotherapy (36% – 41%). In this trial, all patients were treated with a chemotherapy regimen containing either carboplatin (in about a third of patients) or cisplatin plus 5-fluorouracil, and 1 group of patients also received cetuximab (400 mg/m2 as an initial dose, followed by 250 mg/m2 weekly).
Regarding Taxol and cetuximab without platin, a phase II study of cetuximab alone in 103 patients was the first to demonstrate clinical efficacy of a monoclonal antibody as monotherapy in patients with recurrent and/or metastatic SCCHN progressing on chemotherapy. Cetuximab monotherapy led to a response rate of 13%, a disease control rate of 46% and a median overall survival of 5.84 months. Cetuximab has also been shown be active in combination with paclitaxel in the first-line setting. In a phase II study in 42 patients, treatment with once weekly paclitaxel 80 mg/m2 plus cetuximab led to an overall response rate of 60% and a disease control rate of 88%. The median PFS was 5 months, which correlates with that reported with cetuximab plus cisplatin in the study by Burtness et al. At a median follow-up of 5.6 months, the median overall survival had not been reached.
A version of this regimen with weekly Taxol(Hitt et al) found that the combination of cetuximab and weekly paclitaxel is well tolerated and provides very encouraging activity in advanced/recurrent SCCHN. The full data, including biomarker results. In a group of 35 pts. complete responses have been observed in 7 pts, partial responses in 18 pts, and stable disease in 6 pts for an overall response rate of 71% and disease control rate of 88%. 44 pts are evaluable for safety. Main grade 3/4 toxicities(NCI): 8 pts had acne- like rash; 7 neutropenia but only 1 febrile neutropenia; 6 asthenia; 3 mucositis; 2 infusion related reactions to paclitaxel and 1 to cetuximab; 2 peripheral neuropathies; 1 diarrhea; 1 vomiting; and 1 conjunctivitis. When updated in 2011, the authors concluded: “The combination of cetuximab and weekly paclitaxel was active and well tolerated by these poor prognosis patients and may be an option for the treatment of medically unfit patients, particularly those for whom platinum is contraindicated.”
NCCN lists both Taxol and Erbitux but not as a combination. It appears to be a good option for patients who cannot tolerate cisplatin or carboplatin.
R. Hitt, A. Irigoyen, J. Nuñez, J. Grau, J. Garcia Saenz, M. Pastor, C. Jara, C. Garcia Giron, M. Hidalgo, J. Cruz Hernandez
Phase II study of combination cetuximab and weekly paclitaxel in patients with metastatic/recurrent squamous cell carcinoma of head and neck (SCCHN): Spanish Head and Neck Cancer Group (TTCCJournal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 6012
R. Hitt, A. Irigoyen, H. Cortes-Funes, J. J. Grau, J. A. García-Sáenz, J. J. Cruz-Hernandez, and the Spanish Head and Neck Cancer Cooperative Group (TTCC)
Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck Ann Oncol first published online August 23, 2011 doi:10.1093/annonc/mdr367
Thomas J. Lynch, Taral Patel, Luke Dreisbach, Michael McCleod, William J. Heim, Robert C. Hermann, Eugene Paschold, Nicholas O. Iannotti Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099, JCO February 20, 2010 vol. 28 no. 6 911-917
Vermorken JB et al. (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25: 2171-2177
Kies M, Garden A, Holsinger C, et al. Induction Chemotherapy (CT) with Weekly Paclitaxel, Carboplatin, and Cetuximab for Squamous Cell Carcinoma of the Head and Neck (HN). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. June 2006. Abstract # 5520.
Hitt R et al. (2007) Phase II study of combination cetuximab and weekly paclitaxel in patients with metastatic/recurrent squamous cell carcinoma of head and neck (SCCHN): Spanish Head and Neck Cancer Group (TTCC) [abstract #6012]. J Clin Oncol 25 (18S)
L. Licitra, P. Bossi, L. D. Locati, and C. Bergamini Is Restoring Platinum Sensitivity the Best Goal for Cetuximab in Recurrent/Metastatic Nasopharyngeal Cancer?
J. Clin. Oncol., October 20, 2005; 23(30): 7757 – 7758.
JJ Cruz, A Ocaña, E Del Barco and A Pandiella Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer Annals of Oncology 2007 18(3):421-430;