Carboplatin: A clinical review

Yarbro, Connie Henke

doi:10.1016/0749-2081(89)90083-1

Cited by 16 publications

(9 citation statements)

References 27 publications

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“…For instance, a prominent dose-limiting side effect of carboplatin is myelotoxicity (compare section ). , This issue has even been exploited as cytoreductive therapy, an approach to mobilize peripheral-blood progenitor cells in hematological malignancies such as non-Hodgkin’s lymphoma . However, as outlined in section , as early as the discovery of cisplatin as anticancer agent by Rosenberg in the late 1960s, a discussion concerning the contribution of immunological effects was initiated and basically persists until today. ,, Interestingly, stimulated by the remarkable success of Pt-containing chemotherapy with immune checkpoint inhibitors in highly aggressive solid tumors, , the field is currently experiencing an unexpected and urging interest also from the side of pharmaceutical companies.…”

Section: Immunological Effects Of Specific Metal Drugsmentioning

confidence: 99%

Metal Drugs and the Anticancer Immune Response

et al. 2018

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The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.

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Section: Immunological Effects Of Specific Metal Drugsmentioning

confidence: 99%

Metal Drugs and the Anticancer Immune Response

et al. 2018

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“… 50 Carboplatin induces myelotoxicity at maximum tolerated doses. 51 When utilized below the maximum tolerated dose, carboplatin mediates immunostimulatory effects by upregulation of MHC, release of proinflammatory cytokines, and downregulation of immune checkpoint inhibitor proteins, resulting in greater CTL tumor infiltration. 52 , 53 The high-risk individuals either possessed an environment, which reduced the efficacy of chemotherapy, or the degree of myeloablation in these patients was so astringent as to cause a massive bone marrow efflux event upon withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Monocytic Myeloid-Derived Suppressor Cells Underpin Resistance to Adoptive T Cell Therapy in Nasopharyngeal Carcinoma

et al. 2021

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Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-g, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.

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“…Platinum drug resistance is a complex multifactorial phenomenon, resulting from different mechanisms, such as the reduction of intracellular drug accumulation due to the downregulation of transporters and/or to the upregulation of proteins involved in its detoxification or efflux, the failure of the apoptotic pathways and the increase in repair of DNA damage [6,[8][9][10]. Many efforts were devoted to the development of platinum compounds with reduced undesired toxicity, with carboplatin [11] and oxaliplatin [12] reaching the clinic in 1989 and 2002, respectively, demonstrating to be safer than cisplatin [13]. Otherwise, circumventing resistance has proven to be a difficult goal to achieve for anticancer therapy and still represents an intriguing challenge for researchers and clinicians [13,14].…”

Section: Introductionmentioning

confidence: 99%

trans-Dichloro(triphenylarsino)(N,N-dialkylamino)platinum(II) Complexes: In Search of New Scaffolds to Circumvent Cisplatin Resistance

et al. 2022

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The high incidence of the resistance phenomenon represents one of the most important limitations to the clinical usefulness of cisplatin as an anticancer drug. Notwithstanding the considerable efforts to solve this problem, the circumvention of cisplatin resistance remains a challenge in the treatment of cancer. In this work, the synthesis and characterization of two trans-dichloro(triphenylarsino)(N,N-dialkylamino)platinum(II) complexes (1 and 2) were described. The trypan blue exclusion assay demonstrated an interesting antiproliferative effect for complex 1 in ovarian carcinoma-resistant cells, A2780cis. Quantitative analysis performed by ICP-AES demonstrated a scarce ability to platinate DNA, and a significant intracellular accumulation. The investigation of the mechanism of action highlighted the ability of 1 to inhibit the relaxation of supercoiled plasmid DNA mediated by topoisomerase II and to stabilize the cleavable complex. Cytofluorimetric analyses indicated the activation of the apoptotic pathway and the mitochondrial membrane depolarization. Therefore, topoisomerase II and mitochondria could represent possible intracellular targets. The biological properties of 1 and 2 were compared to those of the related trans-dichloro(triphenylphosphino)(N,N-dialkylamino)platinum(II) complexes in order to draw structure–activity relationships useful to face the resistance phenotype.

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Carboplatin: A clinical review

Cited by 16 publications

References 27 publications

Metal Drugs and the Anticancer Immune Response

Metal Drugs and the Anticancer Immune Response

Monocytic Myeloid-Derived Suppressor Cells Underpin Resistance to Adoptive T Cell Therapy in Nasopharyngeal Carcinoma

trans-Dichloro(triphenylarsino)(N,N-dialkylamino)platinum(II) Complexes: In Search of New Scaffolds to Circumvent Cisplatin Resistance

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