Successful Treatment of Small-Cell Lung Cancer With Irinotecan in a Hemodialysis Patient With End-Stage Renal Disease

The prognosis of patients with end-stage renal disease has improved with advances in hemodialysis techniques. However, many patients who undergo hemodialysis suffer from various types of cancer. Limited data is available to guide clinical management of these patients who may have impaired renal function. Here, we report our experience with the use of irinotecan for the treatment of a hemodialysis patient with small-cell lung cancer and end-stage renal disease.

Weekly irinotecan in patients with progressive or rapidly recurrent colorectal cancer pretreated with fluorouracil-based chemotherapy

To prospectively evaluate efficacy and tolerability of weekly irinotecan [CPT-11] in patients with advanced colorectal carcinoma [CRC] that had recurred or progressed following fluorouracil [5-FU]-based therapy. Forty eight patients were enrolled in this study. They were treated with irrinotecan 125 mg/m[2] intravenously [IV] every week for 4 weeks, followed by a 2- week rest. All patients were accessible for toxicity and only 44 patients completed one full course of therapy and were accessable for response. Nine patients [20.5%] attained partial response [95% CI, 10% to 27%] and no cases achieved complete response. The median duration of response was 7 months [range4to 11.5 months]. The median survival time was 10 months [95% CI 8.2 to 13.1 months] and the 1-year survival rate was 43.8% [95% CI, 33% to 53%]. Median time to progression was 4.0 months [95% CI, 2.6 to 5.1 months]. Grade 3-4 diarrhea was observed in 17 patients [35.4%], grade 3-4 nausea and vomiting in 3 patients [6.3%] and 4 patients [8.3%] respectively. Grade 3-4 neutropenia was reported in 5 patients [31.3%]. Grade 3-4 febrile neutropenia or infection affected only 2 patients [4.2%]. Weekly schedule of irinotecan has demon strated significant activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. Diarrhea is the most frequent dose limiting toxicity but can be substantially reduced through appropriate interventional management

Citotoxidad de la beta lapachona: una o-naftoquinona con posibles usos terapeuticos / Cytotoxicity of beta-lapachone, an naphthoquinone with possible therapeutic use

La Beta-lapachona (Beta-lap) es una o-naftoquinona extraída de la madera del lapacho. Las observaciones iniciales mostraron su acción inhibidora del crecimiento del sarcoma de Yoshida y del carcinosarcoma de Walker 256. La Beta-lap genera productos reactivos del oxígeno (ROS: anión superóxido, radical hidroxilo y peróxido de hidrógeno) a los que inicialmente se atribuyó su citotoxicidad. Beta-Lap resultó un potente inhibidor de la síntesis de ADN en T. cruzi, de la topoisomerasas I y II y de la poli(ADP-ribosa) polimerasa (PARP) de diferentes orígenes, enzimas responsables de la conservación del ADN. Se investigó la citotoxicidad de Beta-lap en células de cáncer epidermoide de laringe, melanoma, cáncer de ovario, de mama, de próstata, de pulmón, adenocarcinoma de colon y leucemia, aportando un mejor conocimiento de los mecanismos moleculares involucrados en la acción de Beta-lap y su relación con los procesos de apoptosis y de necrosis. Se comprobó la activación de la calpaina, proteasa cuya actividad depende de tioles, seguida por la activación de quinasas (c-JUN NH2 -quinasa terminal), caspasas y nucleasas, enzimas que degradan al ADN y a las proteínas celulares. Una reacción importante para la actividad de la Beta-lap es su reducción, especialmente por la diaforasa y la NAD(P)H-quinona reductasa, que inician la producción de ROS. La acción de Beta-lap sobre células tumorales resultaría de la inhibición directa de enzimas como las topoisomerasas, PARP y el factor TNF, sumada a la acción de radicales libres. Los efectos citostáticos de ß-lap han abierto interesantes perspectivas para la quimioterapia del cáncer.