Carboplatino

A: Carboplatin, similar to cisplatin, exerts its cytotoxic effect by binding to DNA. [, , ] This binding primarily results in the formation of platinum-DNA adducts, specifically monoadducts and intra- and interstrand diadducts. [] These adducts interfere with DNA replication and transcription, ultimately triggering cell cycle arrest and apoptosis. [, ]

A: Yes, research using accelerator mass spectrometry has demonstrated that carboplatin forms DNA monoadducts at a rate approximately 100-fold slower than cisplatin. [] This difference in the kinetics of DNA adduct formation may contribute to the lower toxicity profile of carboplatin compared to cisplatin. []

A: Studies indicate that carboplatin can enhance the production and persistence of radiation-induced DNA single-strand breaks (SSBs). [] This effect was observed both when carboplatin was administered before irradiation under hypoxic conditions and when added after irradiation during the post-irradiation recovery period in air. [] This suggests a synergistic interaction between carboplatin and radiation therapy.

A: Research on human laryngeal squamous carcinoma cells (HN-3) showed that carboplatin treatment led to down-regulation of epidermal growth factor receptor (EGFR) expression. [] This effect was associated with increased reactive oxygen species (ROS) generation within the cells, indicating a potential mechanism for carboplatin's antitumor activity. []

A: Yes, computational studies have investigated the interaction between carboplatin and a B12N12 nano-cluster. [] This study utilized density functional theory (DFT) calculations with the B3P86 functional to explore the binding interactions and energy differences between various isomers of the carboplatin-nano-cluster complex. []

A: A study on a patient undergoing hemodialysis revealed a significantly lower area under the curve (AUC) of free platinum when carboplatin was administered shortly before hemodialysis. [] This suggests a substantial removal of carboplatin from the systemic circulation during hemodialysis, highlighting the importance of timing chemotherapy administration in this patient population.

A: In vitro experiments utilizing a bovine brain capillary endothelial cell model showed that hyperbaric oxygenation increased the transendothelial permeability of carboplatin. [] This suggests a potential strategy for enhancing carboplatin delivery to the brain, which is particularly relevant for treating brain tumors.

A: Several studies employed various cancer cell lines to investigate the in vitro efficacy of carboplatin, including human laryngeal squamous carcinoma cells (HN-3), [] three glioma cell lines (U251MG, SNB19, and LNZ308), [] two adenocarcinoma cell lines (MiaPaCa and SW480), [] five canine transitional cell carcinoma (TCC) cell lines, [] T24 human bladder cancer cells, [] COR-L23/P human non-small-cell lung carcinoma (NSCLC) cells, [] and two triple-negative breast cancer cell lines (CF41.Mg and MDA-MB-468). []

ANone: Several preclinical studies explored carboplatin-based combination therapies:

• Carboplatin and Difluoromethylornithine (DFMO): Synergistic or additive effects were observed in a majority of the tested glioma and adenocarcinoma cell lines. []
• Carboplatin and Vorinostat (SAHA): Synergy was noted in one glioma cell line and in the MiaPaCa cell line with short exposure times. []
• Carboplatin and Docetaxel: Synergistic effects were observed in two out of three glioma cell lines and in the SW480 cell line with short exposures. []
• Carboplatin and Gemcitabine: Synergistic activity at biologically achievable concentrations was observed in three out of five canine TCC cell lines. []
• Carboplatin and XR5944: Enhanced anti-tumor activity was observed in COR-L23/P human non-small-cell lung carcinoma (NSCLC) xenograft models when XR5944 was administered before carboplatin. []

ANone: Numerous clinical trials have investigated the efficacy and safety of carboplatin in different cancer types:

• Head and Neck Cancer: A retrospective cohort study on US veterans with head and neck squamous cell carcinoma (HNSCC) suggested that carboplatin-based chemoradiotherapy was associated with improved overall survival compared to cetuximab-based chemoradiotherapy. [] This difference was particularly pronounced in patients with oropharynx cancer.
• • A phase III randomized trial found that docetaxel-carboplatin was comparable to paclitaxel-carboplatin in terms of progression-free survival and response rate as a first-line chemotherapy regimen. [] Importantly, docetaxel-carboplatin was associated with significantly less neurotoxicity.
  • A phase II trial explored the combination of gemcitabine/carboplatin with or without trastuzumab as first-line treatment for metastatic breast cancer. [] The regimen demonstrated promising activity, particularly in HER2-positive disease.
  • A retrospective study from Japan evaluated high-dose ifosfamide, carboplatin, and etoposide combined with peripheral blood stem cell transplantation for male germ cell tumors. [] The treatment was found to be feasible and effective with manageable toxicity.
• • A phase II trial evaluated the combination of vinorelbine and gemcitabine as first-line therapy for advanced NSCLC. [] The regimen showed promising activity and tolerability, comparable to standard platinum-based combinations.
  • A phase II study investigated a triplet chemotherapy regimen of carboplatin, paclitaxel, and gemcitabine with amifostine support in advanced NSCLC. [] The combination demonstrated promising activity and good tolerability.
  • A phase III trial compared nab-paclitaxel plus carboplatin to solvent-based paclitaxel plus carboplatin as first-line treatment for advanced NSCLC. [] Nab-paclitaxel plus carboplatin demonstrated a significantly improved overall response rate, particularly in patients with squamous cell histology.
  • A phase II study assessed the feasibility, safety, and efficacy of carboplatin plus S-1 followed by maintenance S-1 therapy for patients with completely resected stage II/IIIA NSCLC. [] The study found that this regimen was not well-tolerated, highlighting the challenges of incorporating carboplatin into adjuvant settings for NSCLC.
  • Glioblastoma: A phase 1/2 clinical trial investigated the feasibility and safety of blood-brain barrier (BBB) disruption using an implantable ultrasound system (SonoCloud-9) in combination with intravenous carboplatin in patients with recurrent glioblastoma. [] The study demonstrated the safety and feasibility of this approach, as well as a substantial increase in carboplatin concentration in the peritumoral brain region.

A: While considered less toxic than cisplatin, carboplatin can still cause side effects. Myelosuppression, particularly thrombocytopenia and neutropenia, is a common side effect of carboplatin treatment. [, , , , ] Other reported side effects include nausea, [] diarrhea, [] hepatotoxicity, [] nephrotoxicity, [] neurotoxicity, [] alopecia, [, , ] and hypersensitivity reactions. [, ] The severity and frequency of side effects can vary depending on the dose, schedule, and combination with other drugs.

A: One study explored the use of hyperbaric oxygenation as a method to enhance the transport of carboplatin across the blood-brain barrier. [] This approach showed promising results in vitro and warrants further investigation in clinical settings.

A: Research has explored the use of folate-targeted PEG as a potential carrier for carboplatin analogs. [] While the folate-targeted conjugates showed efficient cellular uptake via the folate receptor-mediated endocytosis pathway, they formed relatively few DNA adducts and exhibited higher IC50 values compared to carboplatin and non-targeted analogs. [] Further research is needed to optimize the design and delivery of targeted carboplatin conjugates.

ANone: Various analytical techniques have been used to investigate carboplatin, including:

• Accelerator Mass Spectrometry (AMS): Used to measure the kinetics of carboplatin-DNA adduct formation and drug uptake in cells. []
• Fluorescence-Based Microplate Cell Proliferation Assay: Employed to assess the effects of carboplatin on cell proliferation in vitro. []
• Propidium Iodide Staining: Used to evaluate cell cycle distribution in response to carboplatin treatment. []
• Caspase 3 and 7 Enzymatic Activity Measurement: Employed to assess apoptosis induction by carboplatin. []
• Atom Absorbing Spectrometry: Used to measure carboplatin concentration in axillary lymph nodes after regional injection of carboplatin-activated carbon suspension. []
• Immunofluorescence, Western Blotting, and qRT-PCR: Used to assess the expression levels of specific proteins and genes in response to carboplatin treatment. []
• Magnetic Resonance Imaging (MRI): Used to monitor tumor size and drug distribution in preclinical and clinical settings. [, ]

A: Research using a bovine brain capillary endothelial cell model suggests that carboplatin may be a substrate for P-glycoprotein (P-gp), a drug efflux transporter. [] The study demonstrated that verapamil, a P-gp inhibitor, enhanced the transendothelial permeability of carboplatin, similar to its effects on doxorubicin, a known P-gp substrate. [] This finding highlights the potential for drug-transporter interactions to influence carboplatin distribution and efficacy.

A: Yes, cisplatin is another platinum-based chemotherapeutic agent often used in cancer treatment. [, , ] While both drugs share a similar mechanism of action, they exhibit different pharmacokinetic and toxicity profiles. Clinical trials have directly compared carboplatin to cisplatin in various cancer types, such as NSCLC and ovarian cancer, with varying results. [, , ] The choice between carboplatin and cisplatin often depends on factors like tumor type, patient characteristics, and potential side effects.

A: Yes, research is ongoing to identify effective non-platinum-based chemotherapy options for various cancers. For instance, one study explored the combination of vinorelbine and gemcitabine as a potential alternative to platinum-containing regimens in advanced NSCLC. [] This combination demonstrated promising activity and a favorable toxicity profile compared to some platinum-based therapies.

ANone: The research on carboplatin exemplifies the collaborative nature of scientific advancements:

• Medicinal Chemistry: Plays a crucial role in designing and synthesizing carboplatin analogs with improved efficacy, pharmacokinetic properties, and reduced toxicity. []
• Pharmacology and Pharmaceutics: Focus on understanding the absorption, distribution, metabolism, and excretion (ADME) of carboplatin, as well as developing optimal drug delivery systems. [, ]
• Oncology and Clinical Research: Drive the evaluation of carboplatin in clinical trials, investigating its efficacy, safety, and optimal use in different cancer types and patient populations. [, , , , , , , , , , , , ]
• Molecular Biology and Genetics: Contribute to understanding the mechanisms of action, resistance, and potential biomarkers for carboplatin therapy. [, , , ]
• Analytical Chemistry: Develops and refines methods for characterizing carboplatin and monitoring its levels in biological samples. [, , ]
• Biomedical Engineering: Develops novel technologies for drug delivery, such as the implantable ultrasound system used to enhance carboplatin delivery to the brain. []