Development of a high-precision bladder hyperthermic intracavitary chemotherapy device for bladder cancer and pharmacokinetic study

Background Bladder hyperthermic intracavitary chemotherapy (HIVEC) has good effectiveness for bladder cancer, but conventional HIVEC systems lack precision and convenient application. To test the safety of a new HIVEC device (BR-TRG-II-type) in pigs and to perform a preliminary clinical trial in patients with bladder cancer. Methods This device was tested on six pigs to optimize the temperature and time parameters. Then, 165 patients (HIVEC after transurethral resection (TUR), n = 128; or HIVEC, n = 37) treated between December 2006 and December 2016 were recruited. Mitomycin C (MMC) was the chemotherapeutic agent. A serum pharmacokinetic study was performed. The primary endpoints were tumor recurrence, disease-free survival (DFS), and cumulative incidence rate (CIR) during follow-up. The adverse effects were graded. Results The animal experiment showed that 45 °C for 1 h was optimal. HIVEC was successful, with the infusion tube temperature stably controlled at about 45 °C, and outlet tube temperature of about 43 °C in all patients, for three sessions. Serum MMC levels gradually increased during HIVEC and decreased thereafter. The mean DFS was 39 ± 3.21 months (ranging from 8 to 78 months), and the DFS rate was 89.1% during follow-up. No adverse events occurred. Conclusion The use of the BR-TRG-II-type HIVEC device is feasible for the treatment of bladder cancer. Future clinical trials in patients with different stages of bladder cancer will further confirm the clinical usefulness of this device. Trial registration chictr.org.cn: ChiCTR1900022099 (registered on Mar. 252,019). Retrospectively registered.

Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors

The central nervous system (CNS) may be considered as a sanctuary site, protected from systemic chemotherapy by the meninges, the cerebrospinal fluid (CSF) and the blood-brain barrier (BBB). Consequently, parenchymal and CSF exposure of most antineoplastic agents following intravenous (IV) administration is lower than systemic exposure. In this review, we describe the different strategies developed to improve delivery of antineoplastic agents into the brain in primary and metastatic CNS tumors. We observed that several methods, such as BBB disruption (BBBD), intra-arterial (IA) and intracavitary chemotherapy, are not routinely used because of their invasiveness and potentially serious adverse effects. Conversely, intrathecal (IT) chemotherapy has been safely and widely practiced in the treatment of pediatric primary and metastatic tumors, replacing the neurotoxic cranial irradiation for the treatment of childhood lymphoma and acute lymphoblastic leukemia (ALL). IT chemotherapy may be achieved through lumbar puncture (LP) or across the Ommaya intraventricular reservoir, which are both described in this review. Additionally, we overviewed pharmacokinetics and toxic aspects of the main IT antineoplastic drugs employed for primary or metastatic childhood CNS tumors (such as methotrexate, cytosine arabinoside, hydrocortisone), with a concise focus on new and less used IT antineoplastic agents.

Clinical research of the malignant hydrothorax or hydroperitoneum treated with intracavitary chemotherapy and local thermotherapy

19615 Background: Malignant hydrothorax or hydroperitoneum are common complications of the cancer. Pure chemotherapy couldn’t get good effect. We combined intracavitary chemotherapy with local thermotherapy to cure malignant hydrothorax or hydroperitoneum. In order to observe the recent effects and toxicity of thermochemotherapy and evaluate the change of the immunologic function, and to investigate the mechanism of thermochemotherapy. Methods: Fifty-two patients were treated with weekly intracavitary chemotherapy, and then combined with local thermotherapy twice a week. As the control, another fifty patients received weekly intracavitary chemotherapy. Treated for two weeks and rest for one week, and then observed the recent effects and toxicity. Test the level of the T cell subset, NK cells and VEGF in serum and effusion Results: Overall response rate of the malignant hydrothorax was 86.9% vs 60.0% (P<0.05), Overall response rate of the malignant hydroperitoneum was 79.3% vs 46.7% (P <0.01).The incidence of myelosuppression was 7.7% vs 24% (P<0.05). After thermochemotherapy, the ratio of CD4/CD8 rose significantly (P<0.01), but the ratio of NK cells decreased significantly (P<0.05) in malignant hydrothorax or hydroperitoneum. While in peripheral blood, all the ratio of CD3, CD4, CD8, CD4/CD8 and NK cells rose significantly (P<0.05). Meanwhile the level of VEGF decreased significantly (P<0.05) whether in effusion or blood. Conclusions: Combined intracavitary chemotherapy with local thermotherapy could control the malignant hydrothorax and hydroperitoneum effectively with less-toxicity. The cellular immune function was elevated and the neovascularization of tumor was probablely inhibited. No significant financial relationships to disclose.