Title: Predictors and Prognostic Implication of Inability to Complete Prescribed Concurrent Cisplatin Monotherapy in Head and Neck Cancer Patients Treated With Radiation Therapy
Abstract: The addition of cisplatin to radiotherapy (RT) results in improved survival rates in locally advanced head and neck cancer (LAHNC) patients. This comes at the cost of higher toxicity and often results in the inability to complete the prescribed therapeutic regimen. This study investigates outcomes and predictors of inability to complete the prescribed course of concurrent cisplatin monotherapy. We conducted a retrospective chart review of 70 consecutive LAHNC patients treated with concurrent radiation and cisplatin between 2001 and 2011 at our institution. The patients were then separated into 2 groups: (1) able to complete all cycles of prescribed cisplatin regimen, dose reductions allowed and (2) unable to complete all prescribed cycles or changed to another type of systemic therapy. Age, sex, race, ECOG performance status, cisplatin dosing schedule (weekly versus every third week), current smoking, and pretreatment creatinine were analyzed for effect on chemotherapy completion. Overall survival (OS) and local control were calculated from time of first radiation fraction to time of death or local failure, respectively. Frequencies were compared using the Pearson χ2 test. Means were compared using the independent samples t-test, and Kaplan-Meier estimates were compared using the log-rank test. Hazards ratios were generated from Cox proportional hazards models. Of the 70 evaluated patients, 52 patients were characterized in group 1, and 18 patients in group 2. Baseline characteristics between the groups were similar other than patients in group 1 were more likely to be younger (mean age 55.4 versus 62.1 years P=0.008). The Kaplan-Meier estimate of OS at 3 years was 75.3% for group 1 versus 56.9% for group 2 (P = 0.023). The 3 year estimate of local recurrence was 12.9% in group 1 versus 26.5% in group 2 (P = 0.35). Patient age was found to be the only significant predictor of inability to complete prescribed chemotherapy: 14 of 52 (26.9%) patients 60 years or less discontinued planned chemotherapy compared to 8 of 18 (44.4%) patients greater than 60 years (P = 0.027). On univariate analysis, predictors of improved survival included ability to complete chemotherapy (HR 0.44 P=0.027) and use of bolus cisplatin (HR 0.48 P=0.042). Inability to complete the prescribed concurrent cisplatin monotherapy course was associated with inferior survival. In our study, patients over 60 years of age were less likely to complete cisplatin monotherapy compared to younger patients. Although cisplatin remains the standard of care in concurrent chemoradiotherapy with LAHNC patients, alternative systemic agents should be investigated further in patients with advanced age.