New Trends in Chemotherapy Treatment of Pediatric Patients - Essay Example

New Trends in Chemotherapy Treatment of Pediatric Patients and Introduction Cancer is one of the biggest challenges facing health care on a global basis. The impact of controlling the disease has affected the world economy. The American Cancer Society report that the annual costs of cancer in 2009 were estimated to be over $216.6 billion where $86.6 billion was spent on direct medical costs whereas $130 billion was spent on indirect mortality. The American Cancer Society indicates that over 1,600 people die each day due to cancer complications. Brain tumor is the second most common cancer and the most frequent solid tumor in childhood, which account for 4.3 cases per 100,000 in the US (Gottardo & Gajjar, 2008). This essay will cover in details cancer in pediatric patients, giving special focus to brain tumors and the emerging chemotherapy treatment trends being administered to fight cancer in pediatric patients. According to Cabrera and Schub (2014), the most common brain neoplasms in children, and medulloblastoma, which account for 20-30% of all brain tumors in pediatric populations. Although childhood cancer is relatively uncommon, the disease is still a persistent issue among the cancer patients it affects. Childhood Cancer states that Cancer is the second leading cause of children deaths in Canada. Childhood Cancer Canada report that more than 10,000 children are living with cancer currently. The problem is more serious in children since the rate of tumor growth in children is more rapid than in adults. In recent years, medical professionals in the cancer field are coming up with new chemotherapy treatments to enhance the effectiveness of the drugs in order to reduce mortality rate in children. For instance, chemotherapy for treatment of pediatric tumors began as early as 1970s (Robertson, 2006). New trends of cancer treatments such as Metronomic, Bevacizumab, and chemotherapy drugs that pass the Blood Brain barrier, are emerging which aims at saving lives and extending survival for children suffering from cancer. The implementation of the new trends of chemotherapy has caused a major interest of study to identify their effectiveness. Metronomic There has been an ongoing debate between medical researchers concerning the efficacy in tumor killing and lack of toxicity. The issue is highly sensitive especially in treatment of cancer among children due to the high levels of toxicity of the chemotherapy drugs, which the children are exposed to. Although the chemotherapy drugs are effective in disrupting the DNA of the tumor cells hence making them incapable of replicating and thus killing them, the toxicity of these drugs accelerate the diminishing of the quality life for the pediatric patient as well as causing additional ill health to the existing one. According to Gottardo and Gajjar (2008), further application of intensified treatment, using conventional chemotherapy can result to increasing levels of toxics in the brain without advancing the probability of survival. Due to the sensitivity of this issue, there has been a need for a chemotherapy approach that brings into consideration low levels of toxicity. Metronomic chemotherapy entails the application of low quantities of non-toxic doses of chemotherapeutics drugs, through administering them at regular levels. According to Reddy and Wellons III (2003), high-grade gliomas have proved difficult to treat among pediatric patients despite aggressive treatment with multimodal therapy. However, patients who have been subjected to aggressive resection have exhibited a longer survival rate compared to pediatric patients who have undergone only biopsies or partial sections. Traore et al (2013), state that metronomic therapy, may be effective through targeting of cancer cells, tumor-associated angiogenesis, and stimulation of anticancer immunity. This chemotherapy approach has showed significant results in reducing the adverse events that are usually associated with chemotherapy. Metronomic chemotherapy in pediatric patients has showed a high incidence of successful cure although 25% of pediatric cancers are still incurable (Noronha et al., 2013). Although clinical data of metronomic chemotherapy in pediatric oncology is limited, the treatment method is well suited and represents a real alternative solution for children with cancer. Medical professionals have used metronomic combinations, which was able to enhance the stability of the refractory cancer in the pediatric patients and re-induction of tumor dormancy (Traore et al., 2013). This can be explained by the fact that metronomic therapy mechanism involves the inhibition of angiogenesis and immune system, which might lead to tumor dormancy. A research study by Traore et al. (2013) indicates that metronomic regimen can be applied with extremely low quantities of toxics and can facilitate long-term control of the disease. The results also show that there is general improvement of the patient’s health since a patient with a metastatic neuroblastoma showed positive improvement after being treated for more than a year, which led to the clearance of metastatic disease and reduction in size of the primary tumor. However, metronomic therapy is not always effective is permanently eliminating the cancer cells. In many pediatric patients, despite administering the chemotherapy, the persistent ailment remains stable, which confirms the likelihood of metronomic therapy to re-induce tumor dormancy. Metronomic therapy involves administering drugs at dose levels that are close to the maximum tolerated dose (MTD) with a time interval ranging from two to four weeks, which allows the recovery of normal tissues, especially the bone marrow progenitors (Traore et al., 2013). Consequently, the approach leads to acute toxicity of the drugs, as well as long-term effects of cumulative doses. The strategy allows for regrowth of the tumor in the interval period while also leading to emergence of resistant populations of tumor cells (Noronha et al., 2013). Additionally, despite intense doses of metronomic chemotherapy, which causes an upward of 3-log decline in the tumor accumulation, there is incomplete regression and subsequent potential of relapse. Passing the Blood-Brain Barrier in chemotherapy treatment in Pediatric patients Although chemotherapy has demonstrated its efficacy in management of some pediatric brain tumors, inactiveness is a common occurrence in medical trials. Most of these failures can be attributed to the blood-brain barrier (BBB), which hinders the passage of systematically administered chemotherapeutics into pediatric brain tumors by preventing them from entering the tumor lesions in the brain (Wu, Li, Janagam & Lowe, 2014). Various approaches have been implemented, which aim at addressing this issue in order to enhance the effectiveness of the chemotherapeutics. By-passing the blood-brain barrier through directly administering the chemotherapeutics into the brain is one of the most effective strategies. The direct administration of chemotherapeutics also bypasses blood-cerebrospinal fluid (CSF) which forms a formidable obstacle in either oral or intravenous administration of the drugs. The strategy involves two methods of chemotherapeutics administration, intrathecal administration, and convection-enhanced delivery. Intrathecal administration involves injecting the drugs into the fluid-filled space in spine via needle or under the scalp through an outlet catheter, which is connected to the ventricles (Wu, Li, Janagam & Lowe, 2014). The intrathecal chemotherapy has indicated successful results in the treatment of acute lymphoblastic leukemia, neoplastic meningitis, cerebral lymphoma, atypical teratoid rhabdoid tumor, and neuroectodermal tumors such as medulloblastoma and pineoblastoma, germ cell tumors and ependymomas in children. However, intrathecal administration faces the disadvantage of drug distribution in non-targeted areas, inhomogeneous distribution, and ineffective volume of drug distribution. Additionally, the strategy has been inefficient in treatment of intraparenhymal tumor (Wu, Li, Janagam & Lowe, 2014). Convection-enhanced delivery (CED) is a more efficient method compared to the intrathecal approach in drug administration. The method enhances delivery of high concentration of chemotherapeutics directly into the brain tumors through directly connecting intracranial catheters to the target brain tumors hence chemotherapeutics are delivered quickly via convection. The method has been efficient in management and treatment of recurrent brain tumors such as high-grade glioma and glioblastoma. Disrupting the blood-brain barrier is another effective strategy of circumventing the BBB where tight junctions of BBB are opened thus allowing for the passage of chemotherapeutics. Mannitol is the most commonly used hyperosmotic agent in the osmotic approach where the hypertonic solution is infused into the arterial blood, which leads to shrinking of endothelial cells in the BBB to allow the tight BBB junctions to open, hence allowing for chemotherapeutics passage. However, the osmotic approach is non-selective hence; chemotherapeutics are administered into both the normal brains region and the brain tumors. Such exposures may lead to entrance of other substances, which may cause seizures and chronic neurological changes. In addition, delay in recovery of the blood-brain barrier may heighten the risk of neurotoxicity. Additionally, medical professionals have acknowledged active transport across the blood - brain barrier, without disrupting the BBB, as an effective approach of circumventing the blood-brain barrier (Wu, Li, Janagam & Lowe, 2014). The approach has been made possible through utilization of transport mechanisms in the blood-brain barrier to design drug delivery systems that are capable of enhancing drug permeability across the blood-brain barrier. Non-carriers such as polymeric micelles, dendrimers, liposomes, polymer-drug conjugates, and inorganic particles have been extensively used for enhancing delivery of drugs via the blood-brain barrier. Moreover, drug specialists have conjugated cell-penetrating peptides as well as receptor targeting molecules for example, transferrin to the non-carriers to facilitate permeability of the chemotherapeutics via the blood-brain barrier. However, most of the non-carriers are still under experimental testing for delivery of chemotherapeutics into the brain tumors (Wu, Li, Janagam & Lowe, 2014). References American Cancer Society. (2014). Economic Impact of Cancer. Retrieved from http://www.cancer.org/cancer/cancerbasics/economic-impact-of-cancer Cabrera, G., Schub. T. (2014). Brain Tumors in Children Gottardo, N. G., Gajjar. A. (2008). Chemotherapy for Malignant Brain Tumors of Chilhood. Journal of Child Neurology, 23(10), 1149-1159. Noronha, V., Krishna, M., Patil, V., Joshi, A., Banavali, S., Prabhash, K., & others,. (2013). Metronomic therapy: Chemotherapy revisited. Indian Journal Of Cancer, 50(2), 142 Reddy, A., & Wellons III, J. (2003). Pediatric High-Grade Gliomas. The Cancer Journal, 9(2), 107--112. Robertson, P. (2006). Advances in treatment of pediatric brain tumors. Neurorx, 3(2), 276--291. Traore, F., Togo, B., Pasquier, E., Demb\el\e, A., Andr\e, N., & others,. (2013). Preliminary evaluation of children treated with metronomic chemotherapy and valproic acid in a low- income country: Metro-Mali-02. Indian Journal Of Cancer, 50(3), 250  Wu, L., Li, X., Janagam, D., & Lowe, T. (2014). Overcoming the Blood-Brain Barrier in Chemotherapy Treatment of Pediatric Brain Tumors. Pharmaceutical Research, 31(3), 531—540 Read More