sodium-nitrite and Brain-Neoplasms

Systemic administration of nitrite anion seems to be a practical way to produce local burst of nitric oxide, a hypoxic cell radiosensitizer in solid tumors. This randomized controlled pilot study assessed radiologic objective response rate (ORR) in patients suffered from brain metastases treated by whole-brain radiotherapy (WBRT) concurrent with intravenous infusion of sodium nitrite versus WBRT alone. Twenty patients were randomized into the following groups: Ten patients treated by WBRT (30 Gy in ten fractions over 2 weeks) concomitant with 2-hour intravenous infusion of sodium nitrite (267 µg/kg/h) before each fraction of radiation (WBRT + SN arm) and ten patients received the same schedule of WBRT, alone (control arm). ORR was measured according to response evaluation criteria in solid tumors (RECIST version 1.1). There were four radiologic objective responses in WBRT + SN arm compared with three in the control group without significant statistical difference (P = 1.00). In contrast, age ≤ 65 years (P = 0.05) and presence of extra-cranial metastases (P = 0.01) were predictor factors of ORR. In conclusion, intravenous infusion of sodium nitrite with this dose and schedule to patients with brain metastases concurrent with radiotherapy did not show any major benefit in terms of radiologic response.

Topics: Adult; Aged; Brain Neoplasms; Cranial Irradiation; Dose Fractionation, Radiation; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pilot Projects; Radiation-Sensitizing Agents; Sodium Nitrite; Treatment Outcome

Topics: Acupuncture; Brain Neoplasms; Humans; Migraine Disorders; Neovascularization, Pathologic; Placebos; Sodium Nitrite; Vasospasm, Intracranial

Brain tumors are the leading cause of death from childhood cancer, yet the causes of most of these tumors remain obscure. Few chemicals are effective in causing brain tumors experimentally after systemic administration of low doses; a notable exception is one group of N-nitroso compounds, the nitrosamides (in particular the nitrosoureas). Feeding pregnant animals nitrosamide precursors (e.g., sodium nitrite and an alkylamide such as ethylurea) causes a high incidence of nervous system tumors in offspring. This population-based epidemiological study was designed to test the hypothesis that maternal consumption during pregnancy of meats cured with sodium nitrite increases the risk of brain tumors among offspring. The intake of vitamins C and E blocks endogenous formation of nitroso compounds and was expected to be protective. Mothers of 540 children under age 20 with a primary brain tumor diagnosed during 1984-1991 and 801 control children in the same 19 counties on the U.S. West Coast were interviewed. Risk increased with increasing frequency of eating processed meats [odds ratio (OR) = 2.1 for eating at least twice a day compared to not eating; 95% confidence interval (CI) = 1.3-3.2; P = 0.003). Risk also increased with increasing average daily grams of cured meats or mg of nitrite from cured meats (P for each <0.005) but not with nitrate from vegetables. Daily use of prenatal vitamins throughout the pregnancy decreased risk (OR = 0.54; CI = 0.39-0.75). Risk among mothers who consumed above the median level of nitrite from cured meat was greater if vitamins were not taken (OR = 2.4; CI = 1.4-3.6) than if they were (OR = 1.3). These effects were evident for each of three major histological types and across social classes, age groups, and geographic areas. This largest study to date of maternal diet and childhood brain tumors suggests that exposure during gestation to endogenously formed nitroso compounds may be associated with tumor occurrence. Laboratory exploration is needed to: (a) define dietary sources of exposure to alkylamides; (b) investigate the reactivity of nitrite in high concentration such as around bits of cured meats in the stomach after ingestion compared to nitrite in dilute solution; and (c) confirm that simultaneous ingestion of alkylamides and cured meats leads to the endogenous formation of nitrosamides.

Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Diet; Female; Humans; Infant; Male; Meat Products; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Sodium Nitrite; United States; Vitamins