-
Advances in Therapy Oct 2023Trilaciclib was recently approved in the USA for reducing chemotherapy-induced myelosuppression (CIM) among adults with extensive-stage small cell lung cancer (ES-SCLC)... (Review)
Review
INTRODUCTION
Trilaciclib was recently approved in the USA for reducing chemotherapy-induced myelosuppression (CIM) among adults with extensive-stage small cell lung cancer (ES-SCLC) when administered prior to chemotherapy. There is limited understanding of real-world outcomes of trilaciclib.
METHODS
A comprehensive literature review was conducted using a keyword search in the MEDLINE, Embase, and conference abstracts. Additional studies were identified through communications with the authors of relevant studies. Published and unpublished real-world studies of trilaciclib- and comparable non-trilaciclib-treated patients with ES-SCLC were included. Evidence on myelosuppressive hematologic adverse events (HAEs), cytopenia-related healthcare utilization, and other reported outcomes (e.g., hospitalizations, dose reduction, and treatment delay) were synthesized. If feasible, outcomes were compared qualitatively between the trilaciclib and historical reference groups, and between first-line trilaciclib initiators and the overall trilaciclib population. Weighted averages were estimated for selected outcomes using sample size as the weight.
RESULTS
The literature search identified five unique studies based on eight records-two included trilaciclib only, two non-trilaciclib only, and one both. In trilaciclib cohorts, the weighted average prevalence of grade ≥ 3 myelosuppressive HAEs in ≥ 1 lineage, ≥ 2 lineages, and all three lineages was 40.5%, 14.5%, and 7.5%, respectively. All rates were numerically lower compared to the historical non-trilaciclib cohorts (58.8%, 28.0%, 13.0% respectively). Cytopenia-related healthcare utilization was also lower in the trilaciclib cohorts. In general, first-line trilaciclib initiators had numerically lower myelosuppressive HAEs and cytopenia-related healthcare utilization than the overall trilaciclib patients.
CONCLUSIONS
The existing evidence suggests that trilaciclib may reduce single and multilineage grade ≥ 3 myelosuppressive HAEs and cytopenia-related healthcare utilization among patients with ES-SCLC in the real world. It is a promising new treatment for CIM prevention in ES-SCLC and may bring greater benefits to first-line trilaciclib initiators. Future studies are recommended to further evaluate the real-world effectiveness of trilaciclib.
Topics: Adult; Humans; Small Cell Lung Carcinoma; Antineoplastic Combined Chemotherapy Protocols; Lung Neoplasms
PubMed: 37490258
DOI: 10.1007/s12325-023-02601-2 -
Journal of Cancer Research and... 2016Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular... (Meta-Analysis)
Meta-Analysis Review
Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular deoxyribonucleic acid (DNA) by leading covalent bifunctional DNA adducts with cellular DNA. Major side effects of oxaliplatin are neurotoxicity (peripheral neuropathy), myelosuppression with moderate thrombocytopenia and gastrointestinal toxicity (diarrhea). Thrombocytopenia might be related to myelosuppression and/or drug-induced immune thrombocytopenia (DIIT). In here, oxaliplatin-induced thrombocytopenia is discussed with review of the literature.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Gastrointestinal Neoplasms; Humans; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia
PubMed: 27461601
DOI: 10.4103/0973-1482.154056 -
Molecular Medicine (Cambridge, Mass.) Mar 2018Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated... (Review)
Review
Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated erythrocyte.Altered red cell production can result from the direct impairment of medullary erythropoiesis, as seen in the thalassemia syndromes, inherited bone marrow failure as well as in the anemia of chronic disease. Alternatively, in disorders such as sickle cell disease (SCD) as well as enzymopathies and membrane defects, medullary erythropoiesis is not, or only minimally, directly impaired. Despite these differences in pathophysiology, therapies have traditionally been non-specific, limited to symptomatic control of anemia via packed red blood cell (pRBC) transfusion, resulting in iron overload and the eventual need for iron chelation or splenectomy to reduce defective red cell destruction. Likewise, in polycythemia vera overproduction of red cells has historically been dealt with by non-specific myelosuppression or phlebotomy. With a deeper understanding of the molecular mechanisms underlying disease pathophysiology, new therapeutic targets have been identified including induction of fetal hemoglobin, interference with aberrant signaling pathways and gene therapy for definitive cure. This review, utilizing some representative disorders of erythropoiesis, will highlight novel therapeutic modalities currently in development for treatment of red cell disorders.
Topics: Animals; Erythropoiesis; Genetic Therapy; Hematologic Diseases; Humans
PubMed: 30134792
DOI: 10.1186/s10020-018-0011-z -
Integrative Cancer Therapies 2023Cancer treatment remains a significant challenge for the medical community, and improved therapies are necessary to treat cancer and its associated complications.... (Review)
Review
Cancer treatment remains a significant challenge for the medical community, and improved therapies are necessary to treat cancer and its associated complications. Current anticancer therapies often have significant side effects, underscoring the need for new treatment options. Moxibustion is a representative external therapy used in traditional Chinese medicine. This review examines clinical studies demonstrating moxibustion's ability to improve the efficacy of radiotherapy and chemotherapy and control tumor progression. Moxibustion can prevent and treat various complications of cancer, including cancer-related or therapy-induced gastrointestinal symptoms, myelosuppression, fatigue, pain, and postoperative lymphedema. has also been shown to enhance the quality of life for cancer patients. However, very few studies have investigated the underlying mechanisms for these effects, a topic that requires systematic elucidation. Evidence has shown that moxibustion alone or combined with chemotherapy can improve survival and inhibit tumor growth in cancer-bearing animal models. The anticancer effect of moxibustion is associated with alleviating the tumor immunosuppressive and vascular microenvironments. Additionally, the therapeutic effects of moxibustion may originate from the heat and radiation produced during the combustion process on acupoints or lesions. This evidence provides a scientific basis for the clinical application of moxibustion in anticancer treatment and reducing the side effects of cancer therapies and helps promote the precise application of moxibustion in cancer treatment.
Topics: Humans; Moxibustion; Quality of Life; Neoplasms; Fatigue; Medicine, Chinese Traditional; Tumor Microenvironment
PubMed: 37746720
DOI: 10.1177/15347354231198089 -
Current Treatment Options in Oncology Jun 2004Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and... (Review)
Review
Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the marrow. The disease is uncommon and there is a lack of clear diagnostic criteria. WM is treatable but not curable and long-term survival is possible. Therefore, the treating physician needs to carefully balance the risks and benefits of treatment. Treatments are aimed at relieving symptoms resulting from marrow infiltration and the hyperviscosity syndrome. Therapies available for initiation of treatment include alkylating agents, purine nucleoside analogs, and rituximab. Chlorambucil has been the mainstay of treatment for many years and remains useful, especially in older patients. Rituximab has become an important new therapy for this disease because of its positive treatment responses, acceptable toxicity, and lack of therapy-associated myelosuppression and myelodysplasia. Currently, rituximab is being combined with chemotherapy. Other options of treatment include interferon and corticosteroids. Emerging therapies include stem cell transplantation (autologous and allogeneic) for younger patients. Currently, there are few comparative data on which to state an absolute opinion concerning the best available treatment for patients with WM.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Combined Modality Therapy; Decision Trees; Humans; Rituximab; Stem Cell Transplantation; Waldenstrom Macroglobulinemia
PubMed: 15115652
DOI: 10.1007/s11864-004-0015-5 -
Hematology. American Society of... Dec 2016The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming... (Review)
Review
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity. There is also ongoing development of second-generation agents which have the promise of less toxicity than the US Food and Drug Administration (FDA)-approved compounds. In addition, immunotherapy and the role of the microenvironment are becoming increasingly important and have therapeutic implications in the treatment of patients with CLL. Ultimately, investigators need to evaluate how to position these and other new exciting therapies and decide on the ultimate role for chemoimmunotherapy in modern times.
Topics: Antineoplastic Agents; Chromosome Deletion; Chromosomes, Human, Pair 17; Drug Approval; Humans; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Smith-Magenis Syndrome; Tumor Microenvironment; United States; United States Food and Drug Administration
PubMed: 27913472
DOI: 10.1182/asheducation-2016.1.137 -
Brazilian Journal of Otorhinolaryngology 2007Increasing the intensity of radiation therapy and chemotherapy in the management of cancer has increased the incidence of adverse effects, especially oral mucositis. (Review)
Review
UNLABELLED
Increasing the intensity of radiation therapy and chemotherapy in the management of cancer has increased the incidence of adverse effects, especially oral mucositis.
AIM AND METHODS
a bibliographical review was conducted on the definition of oral mucositis, its clinical findings, the incidence, its etiology, the pathophysiology, associated morbidity, prevention and treatment.
RESULTS
current studies define oral mucositis as a very frequent and painful inflammation with ulcers on the oral mucosa that are covered by a pseudo membrane. The incidence and severity of lesions are influenced by patient and treatment variables. Oral mucositis is a result of two major mechanisms: direct toxicity on the mucosa and myelosuppression due to the treatment. Its pathophysiology is composed of four interdependent phases: an initial inflammatory/vascular phase; an epithelial phase; an ulcerative/bacteriological phase; and a healing phase. It is considered a potential source of life-threatening infection and often is a dose-limiting factor in anticancer therapy. Some interventions have been shown to be potentially effective to prevent and treat oral mucositis. Further intensive research through well-structured clinical trials to obtain the best scientific evidence over the standard therapy of oral mucositis is necessary to attain ideal parameters for radiotherapy and chemotherapy.
Topics: Antineoplastic Agents; Humans; Mouth Mucosa; Neoplasms; Radiotherapy; Stomatitis
PubMed: 17923929
DOI: 10.1016/s1808-8694(15)30110-5 -
Blood Reviews Mar 2015The number of available therapies for hematologic malignancies continues to grow at a rapid pace. Unfortunately, many of these treatments carry both central and... (Review)
Review
The number of available therapies for hematologic malignancies continues to grow at a rapid pace. Unfortunately, many of these treatments carry both central and peripheral nervous system toxicities, potentially limiting a patient's ability to tolerate a full course of treatment. Neurotoxicity with chemotherapy is common and second only to myelosuppression as a reason to limit dosing. This review addresses the neurotoxicity of newly available therapeutic agents including brentuximab vedotin and blinatumomab as well as classic ones such as methotrexate, vinca alkaloids and platinums. Although peripheral neuropathy is common with many drugs, other complications such as seizures and encephalopathy may require more immediate attention. Rapid recognition of adverse neurologic effects may lead to earlier treatment and appropriate adjustment of dosing regimens. In addition, knowledge of common toxicities may help differentiate chemotherapy-related symptoms from actual progression of cancer into the CNS.
Topics: Angiogenesis Inhibitors; Animals; Antibodies, Bispecific; Antineoplastic Agents; Brain Diseases; Brentuximab Vedotin; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunoconjugates; Immunotherapy; Neurotoxicity Syndromes; Organoplatinum Compounds; Rituximab; Seizures; Vinca Alkaloids
PubMed: 25445718
DOI: 10.1016/j.blre.2014.09.012 -
American Journal of Hematology Feb 2014Cancer-related anemia (CRA) is due to multiple etiologies, including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin... (Review)
Review
Cancer-related anemia (CRA) is due to multiple etiologies, including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin deficiency due to renal disease, marrow involvement with tumor as well as other factors. The most common treatment options for CRA include iron therapy, erythropoietic-stimulating agents (ESAs), and red cell transfusion. Safety concerns as well as restrictions and reimbursement issues surrounding ESA therapy for CRA have resulted in suboptimal treatment. Similarly, many clinicians are not familiar or comfortable using intravenous iron products to treat functional iron deficiency associated with CRA. This article summarizes our approach to treating CRA and discusses commonly encountered clinical scenarios for which current clinical guidelines do not apply.
Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Malnutrition; Neoplasms; Prevalence; Treatment Outcome
PubMed: 24532336
DOI: 10.1002/ajh.23628 -
Journal of Pediatric Hematology/oncology Oct 2014The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of... (Review)
Review
The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients' ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens to improve therapy for the individual patient.
Topics: Antimetabolites, Antineoplastic; Child; Drug Therapy, Combination; Humans; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 24936744
DOI: 10.1097/MPH.0000000000000206