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Optimum Biological Dose Selection
Published in Atanu Bhattacharjee, Bayesian Approaches in Oncology Using R and OpenBUGS, 2020
The maximum dose of the effective drug within the tolerable limit is called the maximum tolerated dose (MTD). Conventionally, it assumed that increased dose is effective. The best effective dose concluded by one level below the tolerable highest dose [3, 4, 5]. Metronomic chemotherapy (MC) emerges as a therapeutic option in medical oncology [6, 7, 8]. Sometimes, conventional chemotherapy becomes resistant [8, 9, 10]. Development of chemoresistance is a common problem [11]. The alternative of high-dose chemotherapy stands with Metronomic chemotherapy (MC). The MC causes less severe side effects than standard chemotherapy. The MC is marked as low-dose chemotherapy. Now the determination of best effective dose in MC is a challenging task. The predefined biomarker is considered to represent the disease status. The threshold value of a biomarker is required to define the disease status. Thereafter the task is to explore that the MC is most effective to maintain the biomarker’s desired value. The MC is decided by the optimum biological dose (OBD)[12]. In this chapter, we will explore the Bayesian approach to decided the low dose of chemotherapy.
Advances in Chemoradiation Treatment of Locoregionally Advanced Non–Small Cell Lung Cancer
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Michael T. Milano, Yuhchyau Chen
Thus, trials from the EORTC and Yugoslavia demonstrated that concurrent low-dose chemotherapy with concurrent radiation is significantly superior to radiation alone, while an Italian study did not demonstrate such a difference. When systemic doses of chemotherapy are also given sequentially, the benefit of concurrent low-dose chemotherapy is not readily apparent, with some studies revealing a trend in improved survival with concurrent low-dose chemotherapy (53–55). The LAMP study suggests a trend toward a median survival benefit with consolidation versus induction chemotherapy. The question of when full-dose chemotherapy should be given then arises: prior to radiation (induction), concurrently with radiation, and/or after radiation (consolidative). The next section discusses the concurrent delivery of full-dose chemotherapy and radiation, and whether the toxicity of such an approach is acceptable.
Extranodal lymphomas in patients with HIV infection
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Michele Spina, Umberto Tirelli
The prospective studies on the treatment of HIV-NHLs that were performed in the pre-HAART era or that were started before the introduction of the new antiretroviral agents belong to three major research lines: The first approach, followed by American investigators, comprises low-dose chemotherapy protocols that are administered indistinctively to all patients.The second research approach is supported by European investigators and consists of different dose–intensity treatment protocols stratified by outcome (good, intermediate, and poor prognosis).The third research line is again an American approach and includes the administration by continuous infusion chemotherapy to patients that have not been stratified by outcome.
Nodular lymphocyte predominant Hodgkin lymphoma: Experience of Polish Pediatric Leukemia/Lymphoma Study Group
Published in Pediatric Hematology and Oncology, 2021
Tomasz Klekawka, Walentyna Balwierz, Agnieszka Brozyna, Radoslaw Chaber, Agnieszka Dadela-Urbanek, Andrzej Koltan, Justyna Kwasnicka, Malgorzata Mitura-Lesiuk, Katarzyna Muszynska-Roslan, Borys Przybyszewski, Iwona Ruranska, Katarzyna Smalisz, Agnieszka Mizia-Malarz, Teresa Stachowicz-Stencel, Malgorzata Stolarska, Agnieszka Wziatek, Katarzyna Zielezinska, Szymon Skoczen
The main limitation of this study is a relatively low NLPHL patient number. In Poland there are about 60 − 70 pediatric patients (below 18 years of age) with newly diagnosed HL each year (unpublished data). A prospective registry database would be more helpful in collecting more NLPHL cases. There are some other limitations of this study. Chemotherapy regimens used were not uniform and one patient refused the “watch and wait” strategy and decided to choose low dose chemotherapy instead. Notably that in two of our cases chemotherapy as for classical HL was introduced before final central pathological review was available. These patients with low stage NLPHL disease should await prompt pathological verification and start treatment only after NLPHL is confirmed, especially in lower stage HL cases showing CD20 positivity.
Outcomes of juvenile myelomonocytic leukemia patients after sequential therapy with cytarabine and 6-mercaptopurine
Published in Pediatric Hematology and Oncology, 2020
Abdul Wajid M, Aditya Kumar Gupta, Gargi Das, Debasish Sahoo, Jagdish Prasad Meena, Rachna Seth
Although 6-mercaptopurine is probably the drug most commonly used in JMML prior to HSCT, the clinical benefits are not clearly understood. Neither all patients can be offered HSCT in resource limited settings, nor are all patients candidates for HSCT in JMML. Low dose chemotherapy or a “wait and watch” strategy may be adopted for a subset of patients depending upon molecular characterization. Newer insights into the molecular basis of JMML have revealed that genome wide DNA methylation can serve as a biomarker which can be used in risk stratification along with clinical characteristics including age, fetal hemoglobin, and number of somatic mutations.27 Patients with lowest levels of methylation have favorable prognosis and may benefit from careful observation or treatment with low intensity regimens. These may be the patients who “responded” to 6-mercaptopurine and cytarabine in our cohort. Our retrospective evaluation of response to the sequential therapy with 6-mercaptopurine and cytarabine in JMML patients who could not be offered HSCT or were not willing for HSCT showed that it could achieve partial or complete response in select patients. Lilleyman et al and Bergstraesser et al have published results which do support our finding.13,14 In resource limited settings, response criteria based on clinical variables viz; splenomegaly, platelet count, WBC count, extramedullary disease, circulating myeloid precursors and blasts in peripheral blood may be used to monitor the disease.
Recent clinical evidence on metronomic dosing in controlled clinical trials: a systematic literature review
Published in Acta Oncologica, 2020
Viktor Wichmann, Natalja Eigeliene, Jatta Saarenheimo, Antti Jekunen
In the majority of trials, MCT was given as a combination treatment. In a low-dose chemotherapy schedule, side effects remained mild and infrequent. When adding standard therapies in high doses, side effects were not accumulative. There were also less harmful effects on the immune system. In many MCT trials, cyclophosphamide was used to achieve immunomodulatory effects and was frequently combined with other drugs, such as methotrexate or thalidomide. As low-dose chemotherapy does not harm the immune system, it has a less negative effect on the efficacy of immunotherapy. Thus, MCT can be easily combined with existing standard therapies or new targeted therapies or immunotherapies. MCT could also be used as a platform to study synergistic effects, in which positive interactions may be possible to find easily, even when agents themselves have only limited direct tumor effects [1–6].