New Trends in Chemotherapy Treatment of Pediatric Patients - Essay Example

New Trends in Chemotherapy Treatment of Pediatric Patients and The use of standard methods of chemotherapy treatment has faced serious challenges due to the persistence of pediatric malignancies. Despite substantial improvement in the treatment of these malignancies especially brain tumors, the outcome in children’s health has been discouraging. In addition to the unaffordable cost of chemotherapy treatments, the health conditions of the pediatric patients continue to deteriorate due to the negative side effects caused by multimodal therapies. In addition to being ineffective, intensive doses of the standard chemotherapy treatments increase toxicity levels thus affecting the overall health. Due to this, medical professionals have designed alternative chemotherapy treatments that seek to address the side effects generated by the standard chemotherapy and improve the overall health of the pediatric patients. However, the effectiveness of the new trends such as metronomic therapy, circumventing the blood-brain barrier, and application of Bevacizumab monotherapy, raises interesting questions such as whether they can effectively handle the challenge of eliminating malignancies without posing greater threats to pediatric patients. Additionally, since the new methods are under experimental trials, their future is dependent on their efficacy, which has not yet been established. 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 paper will conduct an in-depth analysis of 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 population. 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 addition, according to Barnholtz-Sloan, Severson, Stanton, Hamre, and Sloan (2005), the distribution histological type of tumor also varies significantly according to race. 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 Therapy There has been an ongoing debate among 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 given to the cancer patients. Although the chemotherapy drugs are effective in disrupting the DNA of the tumor cells hence making them incapable of replicating, 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. Metronomic therapy has been necessitated by the need of a novel therapy approach that handles effectively the poor outcomes in children with refractory malignancies (Zapletalova, Andre, Deak, Kyr, Bajciova, & Mudry, 2012). 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, Krishna, Patil, Joshi, Banavali, & Prabhash, 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, Togo, Pasquier, Demb\el\e, & Andr\e, 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 the recurrence 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 (Kobiler, Lustig, & Shapira, 2001). Various approaches have been implemented, which aim at addressing this issue in order to enhance the effectiveness of the chemotherapeutics. Circumventing 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 (Pardridge, 1998). Additionally, the strategy has been inefficient in treatment of intraparenhymal tumor (Wu et al., 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 through 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 et al., 2014). Bevacizumab Most of the chemotherapy treatments are designed to directly attack the fast multiplying cells such as the cancer cells. As such, these types of treatments are often inefficient or cause increased toxicity in the body due to intensive administration of the drug doses. Medical professional have designed alternatives to handle these growing tumors with minimal side effects. Bevacizumab is among the latest humanized antibodies that have been developed to inhibit the development of new blood vessels. The drug is attached to the vascular endothelial growth factor (VEGF), which then inhibits tumors from growing through stopping the tumor from creating new blood vessels to the tumor. According to Avery, Hwang, Jajacki, and Parker (2014), Bevacizumab is a monoclonal antibody, which target vascular endothelial growth factor, and plays the role of preventing angiogenesis. The humanized antibody is under current progress of testing for various malignancies in adult cancer patients although it has not been positively assessed in pediatric patients (Benesch & Urban, 2008). The effectiveness of Bevacizumab has been applied in pediatric patients to test its efficacy of the drug. For instance, a recent study by Avery, Hwang, Jajacki, and Parker (2014) has noted an improvement in the vision quality of children with optic pathway gliomas (OPGS). The treatment’s success rate in the experiment was high since four cases of improvement were noted after using Bevacizumab where standard treatment had failed. Previous treatments using carboplatin-based chemotherapy or proton-beam radiation only provided a temporary relief such as stabilization, without any indication of improvement. In yet another experiment on Phase 1 trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors by Benesch and Urban (2008), the preclinical data obtained suggested that antiangiogenic therapy is an effective in malignant nonepithelial tumors of pediatric patients. In addition, the toxicity levels of Bevacizumab and other antiangiogenic drugs were in moderate concentration and well tolerated by the pediatric patients compared to other cytotoxic drugs. However, preclinical studies have suggested that metronomic schedules increase the putative antiangiogenic activity of drugs such as Bevacizumab (Bouffet, Tabori, Huang & Bartels, 2010). Hence, Bevacizumab can be used as a combination with metronomic therapy to enhance chemotherapy treatment. Although present side effects of antiangiogenic drugs have not been fully clarified, severe treatment-related side effects have not yet been identified in pediatric patients (Benesch & Urban, 2008). However, as the number of pediatric patients being treated with Bevacizumab continues to grow, there is a high likelihood that the instances of side effects will soon be noted in the near future. Data concerning the long-term side effects such as high toxicity of antiangiogenic drugs is in limited qualities since the treatment also focuses on patients suffering from metastatic diseases (Chen & Chamberlain, 2010). Therefore, long-term toxicity of antiangiogenic drugs in pediatric patients should be carefully analyzed and assessed. Despite the fact that Bevacizumab has proved to be effective in the inhibition of tumor growth, medical professionals advise that Bevacizumab monotherapy can be enhanced through combining the treatment with cytotoxic chemotherapy (Benesch & Urban, 2008). In consideration of the future perspective of Bevacizumab monotherapy, the treatment seems safe in pediatric patients. The evaluation of biological markers to measure the effectiveness of antiangiogenic treatment in pediatric patients is more likely to extend to future trials in the medical field. Moreover, the incorporation of antiangiogenic drugs in treatment of optic pathway gliomas should be considered in future clinical applications since current efficacy has been established. Conclusion The ineffectiveness of standard methods of chemotherapy treatment has led to the need of devising of alternative therapies in treatment of persistent malignancies in pediatric patients. Particularly, medical researchers have developed new chemotherapy trends that are aimed at reducing the neurotoxicity levels in pediatric patients, while at the same time improving on the efficiencies in order to eliminate the malignancies with minimal side effects. The new chemotherapy trends include metronomic therapy, Bevacizumab monotherapy, and passing the blood-brain barrier. However, these new trends are still under medical experimentation under different phases. Their approval in the medical field is dependent on their efficiency in reducing mortality rates caused by brain tumors and other persistent malignancies in pediatric patients. Metronomic therapy involves administration of low doses of chemotherapy drugs in regular levels in order to regulate the toxicity of the drugs on the pediatrics’ health. 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. When subjected to prolonged periods, this chemotherapy approach has showed significant results in reducing the adverse events of multimodal chemotherapy. Consequently, pediatric patients who were subjected to this treatment had a higher survival rate compared to the multimodal therapy. However, this approach also faces a shortcoming, 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. On the other hand, passing the blood-brain barrier therapy aims at opening the tight epithelial lining to allow for passage of the chemotherapeutic drugs into the brain tumor lesions. The barrier can be circumvented through either intrathecal administration or convection-enhanced delivery. The chemotherapy approach is effective in treatment of acute lymphoblastic leukemia, neoplastic meningitis, cerebral lymphoma, and atypical teratoid rhabdoid tumor. However, the approach faces the various disadvantages such as allowing entry of unintended substances into the lesions, which can cause adverse effects such as seizures. Consequently, delay in recovery of the blood-brain barrier may heighten the risk of neurotoxicity. Lastly, Bevacizumab chemotherapy involves the use of the Avastin drug to cause the inhibition of tumor growth. The chemotherapy approach plays an important role in preventing angiogenesis. Combined with metronomic approach, Bevacizumab monotherapy can double the effectiveness in treating persistent malignancies. However, the direct side effects of this approach have not yet been established since it is under medical trial. Overall, the new trends of chemotherapy treatments have showed greater outcomes in improving the health conditions of pediatric patients with brain tumors compared to the multimodal therapies. Although their continuous use is still uncertain, the success rate of these chemotherapy trends provides a good platform for clinical centers to adopt these methods in future medical practices. References American Cancer Society. (2014). Economic Impact of Cancer. 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