Taxol, carboplatin, Erbitux for stage IV head and neck cancer – pro
For the treatment of recurrent and/or metastatic head and neck cancer, therapeutic options include re-irradiation and salvage surgery and 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.
Following the observation that the combination of cisplatin plus cetuximab was safe, different clinical trials were performed to test this approach. In a phase III study in metastatic or recurrent SCCHN, 117 patients were randomised to receive cisplatin plus cetuximab, or cisplatin plus placebo. Median PFS was 2.7 months for the control arm and 4.2 months for the experimental arm. Median overall survival was 8.0 months and 9.2 months, respectively. Objective response rates were 10% and 26%. The toxicity was similar in both groups, except for the cutaneous rash associated with cetuximab. Recently, a retrospective evaluation of these clinical trials has been reported. In the study, a total of 330 platinum-refractory patients with recurrent or metastasic SCCHN treated with cetuximab alone or in combination with platinum-based chemotherapy were considered and compared with a historical series of 151 patients. The observed toxicity was mainly cutaneous (69% with the monotherapy treatment and 72% with the combination). The median survival time of around 6 months achieved with cetuximab in platinum-refractory SCCHN is similar to that seen with first-line therapy and represents an increase in survival of 2.5 months compared with platinum-refractory historical controls.
One interpetation of these results is that Erbitux restores platinum sensitivity.
Taking all these data into consideration, the administration of cetuximab in combination with a platinum compound in recurrent or metastatic platinum-resistant SCCHN could be an appropriate therapeutic approach that increases response rate and possibly time to treatment progression, without increased toxicity
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).
I did not find any currently ongoing trials of this combination with either Taxol or Taxotere (except with radiation in stage III) but the consensus of experts is that these results must be confirmed before accepted as standard of care. Per most plan definitions, this renders this combination experimental. NCCN(CHEM-A) does not list this three drug combination for metastatic disease. It does list cisplatin and docetaxel and cisplatin/cetuximab.
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;
nccn.org, head and neck
Vermorken J, Bourhis J, Trigo M, et al. (2005) Cetuximab (Erbitux®) in recurrent/metastatic (R&M) squamous cell carcinoma of the head and neck (SCCHN) refractory to first-line platinum-based therapies. Proc Am Assoc Clin Oncol 501s: (Abstr 5505).
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.