Phase II Multicenter Study of the Antiepidermal Growth Factor Receptor Monoclonal Antibody Cetuximab in Combination With Platinum-Based Chemotherapy in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck

Abstract

The combination of cetuximab and platinum chemotherapy is an active and well-tolerated approach to the treatment of this poor-prognosis patient population with platinum-refractory recurrent or metastatic SCCHN for whom there are no recommended standard therapeutic options.

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

“…Similarly, activity has been reported for cetuximab monotherapy or in combination with a platinum in patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (median time to progression of 2.8 months and median overall survival of 5.8-6.0 months; refs. 92,93). These data have led to the recent approval of cetuximab in the United States and in Europe for use in combination with radiotherapy to treat patients with unresectable head and neck squamous cell carcinoma.…”

“…99). Incidence and severity of rash have been shown to correlate with response and survival (93). Different hypotheses have been proposed to explain the appearance of the acneiform rash.…”

“…Furthermore, gefitinib monotherapy has not produced significant clinical activity in patients with advanced refractory gastric cancer (148). However, pharmacodynamic data Improved objective response rates in second-line (186) Progression-free survival and overall survival benefit vs placebo (79,187) Minimal clinical activity in heavily pretreated patients (188) Minimal clinical activity in first-line (189) No clear clinical activity in pretreated patients however, increased disease stabilization suggests benefit (190) No significant clinical activity (98) Clinical activity as second-line treatment (92) Suggested increased activity in combination with gemcitabine as first-line treatment (97) Clinical activity in combination with platinum as second-line treatment (93) Increase in response rate, suggested survival advantage with the addition of cetuximab to cisplatin as first-line treatment (194) Clinical activity as first-line treatment (130) Survival advantage vs chemotherapy alone (gemcitabine) in first-line treatment (120) Minimal clinical activity (142) Minimal clinical activity (147) Minimal clinical activity (141) Clinical activity reported (139) Suggested increased activity combined with chemotherapy (docetaxel) as first-line treatment (146) The Role of VEGF and EGFR Inhibition…”

Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

“…EGFR activation results in the initiation of key intracellular signaling pathways that promote malignant behaviors, including cell cycle progression, proliferation and survival (Yarden and Sliwkowski, 2001;Mendelsohn and Baselga, 2003). Although monotherapy with EGFR inhibitors has met with only limited success (Cohen et al, 2003;Soulieres et al, 2004), the combination of EGFR inhibitors with radiation therapy or cytotoxic chemotherapy is more promising in head and neck cancer, augmenting response rates and survival (Baselga et al, 2005;Bonner et al, 2006).…”

Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

“…In clinical studies prolonged treatment with cetuximab or matuzumab has generally been well tolerated, with skin reactions such as an acne-like rash being the most common side effect (Baselga et al, 2005;Rao et al, 2008;Seiden et al, 2007). Furthermore, endogenous humoral and cellular anti-EGFR immune responses have been observed in cancer patients (Shomura et al, 2004), suggesting that limited autoimmunity to EGFR is acceptable.…”