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Radiopharmaceuticals for Radionuclide Therapy
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Meltem Ocak, Emre Demirci, Jessie R. Nedrow, Rebecca Krimins
In numerous studies, a response rate of 40–97 per cent with a mean of 70 per cent has been reported. The quality of life of the patients also improved, and a significant decrease in analgesic consumption has been noted. A mild bone marrow toxicity is noted in most the patients. The platelet and white blood cell (WBC) counts have been decreased to the lowest levels in 3–5 weeks but recover in 6–8 weeks after therapy. For the repeated treatments, the main dose-limiting toxicity is bone marrow suppression [73]. Overall, 153Sm–EDTMP has been successfully used for pain control for more than three decades.
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Despite its similarity in chemical structure to vinblastine, vincristine sulfate has a different spectrum of both antitumor activity and side effects. It is used to treat a variety of cancers, including leukemias, lymphomas, and some solid tumors (e.g., breast and lung cancers), and is included in several commonly used drug combination. Notably, it is more neurotoxic than vinblastine but causes significantly less myelosuppression. In particular, the relatively low bone marrow toxicity renders it suitable for combination with drugs that cause more significant bone marrow suppression. It is also used to induce remission in ALL in combination with dexamethasone and L-asparaginase. Vincristine is administered via intravenous infusion and cannot be given orally.
Principles of systemic treatment
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
One of the major dose-limiting toxicities encountered in the use of chemotherapy is bone marrow toxicity. In recent years, the availability of colony-stimulating factors (CSF), in particular, granulocyte colony-stimulating factor (G-CSF), has enabled chemotherapy dose to be intensified within the limits of tolerance of bone marrow. G-CSF is an analogue of naturally occurring growth factors given by subcutaneous injection following exposure to chemotherapy. It stimulates the granulocyte production lines in the bone marrow, reducing the period of neutropenia after intensive chemotherapy. The growth factors currently available have no significant effect on platelet and red cell lines. Their use has also facilitated the process of peripheral blood progenitor cell (PBPC) harvesting, thereby simplifying the use of ultra-high-dose chemotherapy which is being increasingly applied to the treatment of solid as well as haemopoietic tumours.
The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment combinations
Published in Expert Review of Clinical Pharmacology, 2022
Benjamin A. Teply, Emmanuel S. Antonarakis
Given the high likelihood of benefit with olaparib or rucaparib specifically in the setting of altered BRCA1 or BRCA2, relatively early use of PARP inhibition while reserving other therapies for later line is very reasonable. The key toxicity of PARP inhibitors is bone marrow toxicity, and early use while patients have adequate bone marrow reserve is essential. Patients with prostate cancer can be exposed to agents with high rates of bone marrow toxicity, including taxane chemotherapy and radiopharmaceuticals. Furthermore, given that bone pain is common in later stages of the disease, patients may also be repeatedly treated with palliative radiotherapy further limiting bone marrow reserve. Finally, end-stage prostate cancer to bone can be associated with myelophthisic bone marrow failure. While there were early signals of concern for the development of myelodysplastic syndromes from PARP inhibition in ovarian cancer studies, most of the marrow toxicity from PARP inhibitors is reversible. Therefore, it may be preferable to use the PARP inhibitor prior to these other potentially myelotoxic agents.
Improving long-term survival in diffuse intrinsic pontine glioma
Published in Expert Review of Neurotherapeutics, 2020
James Felker, Alberto Broniscer
Standard focal conformal fractionated radiation therapy (RT) remains the standard treatment of DIPG. The typical dose of RT is 30 fractions of 1.8 Gy for a total of 54 Gy [48]. Multiple attempts to hyperfractionate RT up to 66 to 75.6 Gy of radiation [49] failed to show an improvement in PFS or OS when compared to standard radiotherapy [50–52]. Conversely, attempts at hypofractionated RT to 5 Gy daily at a total of 25 Gy [53] narrowly failed to meet non-inferiority outcomes when compared to standard dose RT but did show improvement in the quality of life [54]. Several trials have tried to improve on the biologic effects of RT by adding radiation-sensitizer medications. A large review of 44 studies utilizing radiation-sensitizing agents showed a slight increase in median OS and PFS when compared to studies without radiosensitizers. It is difficult to directly compare these studies because of the heterogeneity of treatments and the lack of molecular information on most of the trials [49]. They also reported significant bone marrow toxicity in patients with concurrent treatments during RT [49]. Palliative re-irradiation after progression has been shown to be feasible, well tolerated in selected patients, as well as to improve symptoms and prolong survival by additional few months [55–57].
The bone marrow stromal niche: a therapeutic target of hematological myeloid malignancies
Published in Expert Opinion on Therapeutic Targets, 2020
Lena Behrmann, Jasmin Wellbrock, Walter Fiedler
These different clinical diseases are a result of uncontrolled hematopoiesis driven by intrinsic genetic and epigenetic mutations but also by abnormal modifications of the bone marrow stroma. We performed literature searches using PubMed Database with key words of myeloid malignancies and bone marrow microenvironment from 2000 to February 2020 and followed the development in the field by analyzing the abstracts of the meetings of the American Society of Hematology (ASH) and European Hematological Assocation (EHA) from the years 2016 to 2019. Here, we summarize the concept of the bone marrow niche and current developments in niche targeting therapies for AML, MDS and MPN. For many years the bone marrow microenvironment was considered to be an inert scaffold, providing structures and metabolic support for the HSPCs. In the past decades, however, the bone marrow microenvironment was identified as an active influencer of the homeostasis of hematopoiesis that can aid and abet neoplastic disease progression [5,6]. According to these findings, bone marrow is one dose-limiting factor for cancer therapy, since chemotherapy and irradiation have a high toxicity for hematopoietic and non-hematopoietic cell compartments. These temporary and irreversible damages leads to impaired hematopoiesis with prolonged myelosuppression [7–10]. Therefore, treatment strategies that target the bone marrow microenvironment of malignant cells might overcome bone marrow toxicity and be a useful strategy to attenuate myeloid malignancies or to overcome resistance mechanisms against chemotherapeutic agents.