Comparing high-dose cisplatin with cisplatin-based combination chemotherapy in definitive concurrent chemoradiation setting for locally advanced head and neck squamous cell carcinoma (LAHNSCC).

BACKGROUND: High-dose cisplatin (Cis) is a preferred systemic agent for concurrent chemoradiation (CRT) in locally advanced head and neck squamous cell cancer (LAHNSCC) patients. As some patients are unable to tolerate Cis, this study compares the toxicity and efficacy of weekly cisplatin-paclitaxel (CP) regimen with Cis. METHODS: Patients with LAHNSCC receiving definitive chemoradiation either with Cis (Cisplatin-100 mg/m2 q3w x 3) or CP (Cisplatin-20 mg/m2 ; Paclitaxel-30 mg/m2 qw x7) were included. RESULTS: Cis and CP groups were comprised of 114 and 111 subjects, respectively. Complete response for Cis versus CP groups was 88% versus 88%, respectively. Median follow-up for the study was 58.5 months. After adjusting for potential treatment selection bias, no significant differences were evident between Cis and CP groups for overall survival (hazard ratios [HR] 0.85, 95% CI 0.59-1.21, P = 0.36), progression free survival (HR 0.88, 95% CI 0.62-1.24, P = 0.46), locoregional control (HR 0.77, 95% CI 0.52-1.15, P = 0.21), and distant control (HR 0.87, 95% CI 0.61-1.23, P = 0.42). Patients in the CP group had less acute and chronic toxicities. CONCLUSIONS: Weekly CP regimen can serve as an alternative systemic therapy with radiation in patients with LAHNSCC who are not fit for Cis.

Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.