Treatment Completion, Survival, and Relapse Rates in Patients Treated With Weekly Cisplatin 40 mg/m 2 Concurrent With Head and Neck Irradiation

Abstract

Bolus cisplatin (BC [100 mg/m2]) concurrent with head and neck radiation therapy (RT) is associated with high rates of toxicity and a poor completion rate. Weekly cisplatin (WC [40 mg/m2]) has been used in our institution since 2003. We present the rates of radiation and chemotherapy treatment completion, elapsed radiotherapy time, overall survival (OS), disease free survival (DFS), and distant metastasis free survival (DMFS) using WC, BC, or cetuximab. We reviewed 336 consecutive cases of head and neck cancer treated with concurrent WC x 6 cycles (n=234), BC x 3 cycles (n=50), or cetuximab with 1 induction and 6 weekly concurrent cycles (n=52) from 2003 to 2015. Definitive RT was prescribed to 66-70 Gy in 2.0-2.25 Gy fractions (median 67.5 Gy in 2.25 Gy fractions) and adjuvant RT was prescribed to 60 to 67.5 Gy in 2.0-2.25 Gy fractions (median 66 Gy in 2.0 Gy fractions). IMRT was generally used except for the oral tongue. Treatment stoppage and/or breaks were triggered by Stage III or IV acute toxicity or patient wishes. Chi-square was used to determine differences across groups and Kaplan-Meyer with the log rank test was used in survival analyses. Three hundred thirty-six cases were analyzed with a mean follow up of 31 months. Primary site was oropharynx in 211, oral cavity in 47, larynx in 46, hypopharynx in 14, nasopharynx in 12, and unknown primary in 6. HPV was positive in 75 of 89 (84%) oropharynx cases where HPV status was known. AJCC staging was stage I in 2, stage II in 10, stage III in 36, and Stage IVA/B in 288. Histology was squamous cell carcinoma in 329/336 patients. Stage, primary site, and HPV status were balanced across treatment groups. The full prescribed course of radiation was completed in 224/234 (96%) patients receiving WC, 48/50 (96%) of patients receiving BC, and 44/52 (85%) patients receiving cetuximab (p=0.01). The full course of concurrent chemotherapy was completed in 205/234 (88%) patients receiving WC, 7/50 (14%) patients receiving BC (44 [88%] completed at least 2 cycles), and 42/52 (81%) patients receiving cetuximab (p<0.01). The mean cumulative dose of cisplatin given was 221 mg/m2 for patients receiving weekly cisplatin and 204 mg/m2 for patients receiving bolus cisplatin (p=0.62). There was no difference in mean elapsed treatment time between groups. For patients treated definitively with concurrent WC, BC, and cetuximab, median OS was 121 mo., 76 mo., and 51 mo. respectively (p=0.04 for weekly cisplatin vs. cetuximab, NS for other comparisons); and median DFS was 121 mo., 75 mo., and 38 mo. respectively (p=0.02 for WC vs. cetuximab, NS for other comparisons). At 3-years, distant metastases had developed in 12/324 (4%) patients receiving WC, 4/50 (8%) patients receiving BC, and 2/52 (4%) patients receiving cetuximab with no differences in DMFS. Concurrent WC with head and neck irradiation is associated high rates of chemotherapy and RT completion and compares favorably to BC and cetuximab in OS, DFS, and DMFS.