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The Relationship of Cetuximab-Induced Rash and Survival in Patients with Head and Neck Cancer Treated with Radiotherapy and Cetuximab

2005; Elsevier BV; Volume: 63; Linguagem: Inglês

10.1016/j.ijrobp.2005.07.126

1879-355X

James A. Bonner, Paul M. Harari, J. Giralt, Roger Cohen, José Baselga, David Raben, Dong M. Shin, Roger Ove, Jacek Jassem, Nadia Amellal, N. Azarnia, K. Kian Ang,

Lung Cancer Treatments and Mutations

Purpose/Objective: Agents that inhibit epidermal growth factor receptor (EGFr) signaling are known to induce a characteristic follicular rash. This rash frequently involves the skin of the face and upper thoracic region. The severity of the rash has been associated with improved clinical outcomes for patients with various tumors who have undergone a variety of treatments incorporating EGFr inhibitors. This study was undertaken to assess the relationship of the cetuximab-induced rash and survival in a large cohort of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with radiotherapy and cetuximab. (Cetuximab is monoclonal antibody that targets the extracellular ligand binding domain of EGFr). Materials/Methods: The patients studied herein were part of a previously reported Phase III trial that demonstrated improved survival for radiotherapy and cetuximab compared to radiotherapy alone in patients with stage III or IV locoregionally advanced SCCHN (IJROBP 60(1), S147, 2004). The patients who received radiotherapy and cetuximab were studied to assess the relationship between cetuximab-induced rash and survival. The patients received radiotherapy to the primary tumor and regional lymphatics with the following fractionation regimens: Once-a-day (2.0 Gy × 35 fractions), twice-a day (1.2 Gy × 60–64 fractions) or concomitant boost (1.8 Gy × 30 fractions with a second daily fraction of 1.5 Gy for the last 12 treatment days). Cetuximab was delivered as a 400mg/m2 loading dose (I.V.) one week prior to radiotherapy, followed by 7 weekly I.V. doses of 250mg/m2 during radiotherapy. The N.C.I. Common Toxicity Criteria (NCI-CTC) was used to assess skin toxicity. Grade 3 skin toxicity was modified slightly to include confluent desquamation, uncontrollable pain or erosion of the skin. Kaplan-Meier estimates were used to assess survival. Results: From April 1999 through March 2002, 424 patients were entered on the randomized trial, and 208 of the 211 patients who received radiotherapy and cetuximab were evaluable for this review. Patients were included in the minimal rash group (MRG: 76 patients) if they had grade 0–1 skin toxicity. Patients were included in the prominent rash group (PRG: 132 patients) if they had grade 2–4 skin toxicity. The two groups were well balanced with respect to age, gender, T stage, nodal involvement and the radiation fractionation regimen that was utilized. The evaluation of Karnofsky Performance Status (KRS) revealed that the 90% KPS / 80% KPS ratio was significantly greater in the PRG compared to the MRG (p=0.02). The distribution of patients at other KPS levels was similar between groups. Conclusions: The results of this study strongly suggest a correlation between a more prominent cetuximab-induced rash and improved survival for patients with locoregionally advanced SCCHN who are treated with radiotherapy and cetuximab. This retrospective analysis of rash is subject to potential unanalyzed confounding variables. However, the results warrant future evaluation with additional follow-up of this cohort of patients. Tabled 1()* = 95% confidence limits ()* = 95% confidence limits