sodium-bicarbonate and Neutropenia

Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer.. Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water.. Twenty-five patients who had prior treatments of etoposide and platinum containing regimens (16 refractory patients and nine relapsed patients) were entered. The mean dose-intensities of CPT-11 and cisplatin were 154.8 and 77.4 mg/m(2) per course, respectively. Therefore, 86% of the planned dose was delivered. There were 20 partial responses and an overall response rate of 80% (95% confidence interval, 62-96%) was obtained. The median time to progression and the median survival after starting this regimen were 3.6 and 7.9 months, respectively. The major toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 24 and 12% of patients, respectively. One patient with febrile neutropenia was experienced, and Grade 3 diarrhea was observed in 8%. But there was no treatment death.. Weekly administrations of CPT-11 plus cisplatin together with Oral Alkalization and Control of Defecation provide a practical and well tolerated regimen that was active for refractory or relapsed small cell lung cancer.

Topics: Aged; Antacids; Antidiarrheals; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Irinotecan; Lung Neoplasms; Magnesium Oxide; Male; Middle Aged; Neutropenia; Sodium Bicarbonate; Survival Analysis; Treatment Outcome; Water

We describe the feasibility and safety of an oral administration schedule of hydration, alkalinization and leucovorin rescue with an ambulatory high-dose methotrexate regimen.. From January 2016 to June 2018, 49 ambulatory high-dose methotrexate courses were given to 18 patients. No dose reduction was required afterwards. All patients completed succesfully the planned three doses in an outpatient basis, except four patients, one of them due to pneumonitis. Previous to methotrexate infusion, urinary pH > 7 was achieved in 35 (79.5%) cycles. Methotrexate clearance was achieved by 72 h in 35 courses (71.4%), and by 96 h in 100%. Neutropenia/trombocytopenia grades III/IV were observed in four cycles (8.16%) and two (4.08%) cycles, respectively. Around 20.40% were associated with stomatitis, 14.20% vomiting, 10.20% asthenia, 8.16% diarrhea and 6.12% with renal toxicity.. Ambulatory administration of high-dose methotrexate as CNS prophylaxis is safe and feasible following the described approach, allowing us to optimize healthcare resources.

Topics: Adult; Aged; Ambulatory Care Facilities; Diarrhea; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neutropenia; Prospective Studies; Sodium Bicarbonate; Vomiting; Young Adult

SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied. The aim of this study was to investigate the relationship between oral alkalization drugs and neutropenia in irinotecan-treated patients.. Patients with cervical or ovarian cancer were administered irinotecan and investigated by medical chart reviews to determine whether oral alkalization drugs were effective at ameliorating irinotecan-induced neutropenia. The drug combination in the oral alkalization drugs-ursodeoxycholic acid, magnesium oxide, and sodium hydrogen carbonate-significantly improved neutrophil counts and reduced dose intensity compared with those of non-users. In the large-scale Japanese Adverse Drug Event Report database, the reporting odds ratio of irinotecan-induced neutropenia was significantly lower when irinotecan had been given in combination with oral alkalization drugs.. These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely.

Topics: Adult; Aged; Antacids; Antineoplastic Agents, Phytogenic; Buffers; Camptothecin; Cholagogues and Choleretics; Diarrhea; Female; Humans; Intestines; Irinotecan; Magnesium Oxide; Male; Middle Aged; Neutropenia; Retrospective Studies; Sodium Bicarbonate; Topoisomerase I Inhibitors; Ursodeoxycholic Acid; Uterine Cervical Neoplasms; Uterine Neoplasms

Mitochondrial cytopathy is a multisystemic disease that requires different pharmacological and specialist approaches; although most therapies are usually of scarce effectiveness. We describe a clinical management of a very young girl with Pearson's syndrome that developed the symptoms of Kearns-Sayre syndrome. Many of symptoms were temporarily improved by the replacement therapy with hydrocortisone introduced to treat the partial adrenal insufficiency. During her life, she showed an ample clinical spectrum of symptoms because of multiple organs involvements: firstly bone marrow and, thereafter, brain, retina, inner ear, and kidney. Partial adrenal insufficiency, rarely described in mitochondrial disorders, was a distinctive characteristic of this case. When our patient was treated with hydrocortisone, in addition to ubiquinone and carnitine, the episodes of decompensation regressed and an improvement of the adrenal insufficiency, but only temporary reversion of the weakness of muscle, ophthalmoplegia and of the fatigue, were testified. Nevertheless, after a brief period of recovery, she developed the de Toni-Debré-Fanconi syndrome and the reappearance of the neurological symptoms.

Topics: Acidosis, Lactic; Bone Marrow Diseases; Calcium; Child, Preschool; Disease Progression; DNA, Mitochondrial; Ergocalciferols; Fanconi Syndrome; Female; Humans; Kearns-Sayre Syndrome; Levetiracetam; Neutropenia; Nootropic Agents; Pancreas, Exocrine; Pancreatic Diseases; Piracetam; Sodium Bicarbonate; Thrombocytopenia

Epidemiological studies have suggested an association between antacid therapy and development of listeriosis in humans. In this study we used a neutropenic mouse model to demonstrate that oral administration of sodium bicarbonate shortly before intragastric (i.g.) inoculation with Listeria monocytogenes EGD (serotype 1/2a) significantly increased the severity of the resulting systemic infection. An explanation for this observation is provided by evidence that L. monocytogenes EGD is rapidly inactivated in synthetic gastric fluid at pH below 5. A second strain of L. monocytogenes (CM [serotype 1/2b]) exhibited little ability to cause systemic infection following i.g. inoculation and was not significantly enhanced by administration of sodium bicarbonate. Strain CM was readily inactivated in synthetic gastric fluid even at pH 7. These data suggest that gastric acidity and enzymes provide some innate defense against gastrointestinal listeriosis in neutropenic mice.

Topics: Animals; Animals, Outbred Strains; Disease Models, Animal; Disease Susceptibility; Female; Gastric Acid; Listeriosis; Liver; Mice; Mice, Inbred ICR; Neutropenia; Sodium Bicarbonate; Spleen