Cetuximab in recurrent and/or metastatic salivary gland carcinomas: A phase II study.
ABSTRACT EGFR overexpression in salivary gland carcinomas provides the rational for the investigation of anti-EGFR treatments in recurrent and/or metastatic salivary gland cancers (RMSGCs). The activity of cetuximab in terms of clinical benefit rate (CBR) defined as the occurrence of objective response (CR or PR) or stable disease (SD) for >or=6months was investigated. From April to December 2005, 30 patients [23 adenoid cystic carcinoma (ACC) and 7 non-ACC] were treated with cetuximab at 400mg/m(2)/week followed by 250mg/m(2)/week until progression, major toxicity or voluntary discontinuation. EGFR expression and gene status were retrospectively analyzed by immunocytochemistry and fluorescence in situ hybridization, respectively. A median of 14 courses of cetuximab (range 5-54) were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene amplification and an increased EGFR copy number was observed in 12% of samples, all ACC. Skin rash >or=G2, EGFR overexpression and EGFR copy number were not statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting agents are advisable and should take place by appropriate tumor biological selection, differentiating ACC from non-ACC.
Article: KRAS status and epidermal growth factor receptor expression as determinants for anti-EGFR therapies in salivary gland carcinomas.[show abstract] [hide abstract]
ABSTRACT: Salivary gland carcinomas (SGC) are rare cancers with poor prognosis and limited response to conventional chemotherapy. New strategies based on molecular targeted therapy are needed and the EGFR signaling cascade is considered a possible key pathway for therapeutic molecules. We have analyzed 65 SGC of the main histopathological types for the expression of EGFR and and the mutation status of its downstream effector KRAS. EGFR overexpression (+2, +3) has been identified by immunohistochemistry in 75.4%. KRAS mutation analysis was performed by direct genomic sequencing and revealed a KRAS wildtype in 98.5% except of one adenoid cystic carcinoma with a GGT-GAT transition at codon 12 (Gly12Asp). EGFR overexpression and KRAS wildtype are prerequisites for a successful anti-EGFR therapy. The results of this study plead in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies in SGC.Oral Oncology 05/2009; 45(9):826-9. · 2.86 Impact Factor
Article: Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux® and particle therapy].[show abstract] [hide abstract]
ABSTRACT: Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent leading to the establishment of particle therapy in this indication. However, even modern techniques leave space for improvement of local control by intensification of local treatment. Radiation sensitization by exploitation of high EGFR-expression in ACC with the EGFR receptor antibody cetuximab seems promising. The ACCEPT trial is a prospective, mono-centric, phase I/II trial evaluating toxicity (primary endpoint: acute and late effects) and efficacy (secondary endpoint: local control, distant control, disease-free survival, overall survival) of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 49 patients with histologically proven (≥R1-resected, inoperable or Pn+) ACC. Patients receive 18 GyE carbon ions (6 fractions) and 54 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy. The primary objective of ACCEPT is to evaluate toxicity and feasibility of cetuximab and particle therapy in adenoid cystic carcinoma. Clinical Trial Identifier: NCT 01192087. EudraCT number: 2010 - 022425 - 15.BMC Cancer 01/2011; 11:70. · 3.01 Impact Factor
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ABSTRACT: In this review we present recent progress in diagnostic workup, prognostic evaluation, treatment options and resulting outcomes. Whenever possible, complete resection remains the mainstay of treatment. Sacrifice of facial nerve branches is reserved for the clinically or electromyographically dysfunctioning facial nerve. Clinical or radiological neck disease demands combined surgery and radiotherapy. Treatment of the N0 neck is indicated for advanced stage-high grade tumors but the question remains unanswered whether this should be surgical or radiotherapeutic elective treatment. Surgery alone will cure low stage, low grade tumors, that show no additional negative prognostic factors following adequate resection. In all other tumors postoperative radiotherapy will improve locoregional control. This approach results in good locoregional control, in a way that distant metastasis remains the typical presentation of treatment failure. In this setting, the results of systemic treatment today remain limited, but a huge effort in the molecular biology field has been done to introduce targeted therapy into this domain of head and neck cancer. Disease control remains variable within the patient population. This variation can increasingly be predicted by systems that incorporate the combined information of multivariately identified and quantified prognostic factors into an individualized prognosis for the parotid carcinoma patient.Indian journal of surgical oncology. 04/2010; 1(2):96-111.