Disease relevance of H2cbdca

• METHODS: We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel [1].
• In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1 alpha after carboplatin had minimal thrombocytopenia (nadir, 91,000 to 332,000 platelets per cubic millimeter) [2].
• BACKGROUND: Hematologic toxicity of an antineoplastic drug, carboplatin, is largely dependent on its pharmacokinetics [3].
• Two phase I studies of carboplatin dose escalation in chemotherapy-naive ovarian cancer patients supported with granulocyte-macrophage colony-stimulating factor [4].
• Hypersensitivity reactions to carboplatin [5].

Psychiatry related information on H2cbdca

• Carboplatin dosing: gender bias and inaccurate estimates of glomerular filtration rate [6].
• Defining carboplatin ototoxicity as an increase of greater than or equal to 30 dB in auditory thresholds that was unexplainable by other causes, we identified 5 examples (19%) [7].
• A Phase III trial of BMS-275291, a broad-spectrum MMPI in combination with paclitaxel and carboplatin is open for patients with advanced NSCLC [8].
• RESULTS: At 23 mg/m2 of carboplatin, two patients had WHO grade 3 lethargy and myelosuppression, which were the dose-limiting toxicities [9].
• AC response latencies were largely unaffected by carboplatin [10].

High impact information on H2cbdca

• The cells promoted a rapid and sustained hemopoietic recovery when transplanted after treatment with high-dose etoposide (1500 mg per square meter of body-surface area), ifosfamide (12 g per square meter), carboplatin (750 mg per square meter), and epirubicin (150 mg per square meter) [11].
• Re: Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer [12].
• In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion [13].
• PURPOSE: A population pharmacokinetics study was undertaken to determine a relationship between carboplatin clearance and patient characteristics [3].
• Neutropenia was dose limiting at the carboplatin target AUC of 12 mg.min/mL [14].

Chemical compound and disease context of H2cbdca

• Between March 1985 and January 1987, 103 women with histologically proven stage III-IV ovarian carcinoma were randomly allocated to groups receiving monthly intravenous regimens of 1 g of cyclophosphamide/m2 plus either 60 mg of cisplatin (CDDP)/m2 or 150 mg of carboplatin (CBDCA)/m2 for 1 year unless disease progressed earlier [15].
• CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin [16].
• PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3) [17].
• Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial [18].
• A phase I-II trial of induction chemotherapy with carboplatin and fluorouracil in locally advanced head and neck squamous cell carcinoma: a report from the UCL-Oncology Group, Belgium [19].

Biological context of H2cbdca

• Cohorts of at least three patients received carboplatin at an initial target AUC of 6 mg.min/mL, with escalations of 2 mg.min/mL in subsequent cohorts [14].
• In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin [20].
• Mice rendered pancytopenic with 500 rads and 1.2 mg of carboplatin had a nadir platelet count of five percent of the baseline [21].
• Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice [22].
• Transfusion of positively selected CD34+ cells (2.5 x 10(6) CD34+/kg; range, 0.45 to 5.1) after high-dose VP16 (1,500 mg/m2), ifosfamide (12 g/m2), carboplatin (750 mg/m2), and epirubicin (150 mg/m2) (VIC-E) in 15 patients resulted in a rapid and stable engraftment of hematopoiesis without any adverse events [23].

Anatomical context of H2cbdca

• Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors [24].
• PURPOSE: The tolerance for and activity of escalating targeted doses of carboplatin combined with ifosfamide and etoposide (ICE) were assessed in children with advanced germ cell tumors or other rare solid tumors for which no standard therapy exists [14].
• Diethyldithiocarbamate (DDTC) has been found to protect the bone marrow, kidneys, and gastrointestinal tract from the toxic effects of cisplatin and carboplatin (CBDCA) in animal models [25].
• CFU-Meg were more resistant to paclitaxel alone, or in combination with carboplatin, than CFU-GM and BFU-E [26].
• In the panel of small cell lines, whereas the ranking of sensitivity to carboplatin and cisplatin were similar, each of the other compounds provided individual patterns of sensitivity [27].

Associations of H2cbdca with other chemical compounds

• METHODS: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol [28].
• Individualized carboplatin doses were calculated to achieve a target area under the concentration x time curve (AUC) and adjusted for the glomerular filtration rate (estimated by 99mTc-labeled diethylene-triamine pentaacetic acid clearance) [14].
• Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies [29].
• Chemotherapy comprised vincristine 1.5 mg/m2 weekly for 10 weeks and four cycles of etoposide 100 mg/m2 daily for 3 days, and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.5 g/m2 [30].
• Dose-response curves of melphalan, cisplatin, carboplatin, doxorubicin, and etoposide for the cell line panel were determined by measuring cytotoxicity with a 96-well-plate digital imaging microscopy (DIMSCAN) microassay [31].

Gene context of H2cbdca

• Loss of p53 function was selectively achieved by transduction of human papillomavirus 16 E6 (which degrades p53) into two drug-sensitive neuroblastoma cell lines with intact p53, causing high-level drug resistance to L-PAM, carboplatin, and etoposide [32].
• The influence of these transporters on the pharmacodynamics of cisplatin, carboplatin, and oxaliplatin was investigated using human Menkes' disease fibroblasts (Me32a) that do not express either transporter and sublines molecularly engineered to express either ATP7A (MeMNK) or ATP7B (MeWND) [33].
• These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas-sensitive pathway leading to apoptosis [34].
• Neutralizing anti-Fas (APO-1/CD95) and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death [34].
• MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same [35].

Analytical, diagnostic and therapeutic context of H2cbdca

• Interleukin-1 alpha can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy [2].
• High-dose carboplatin (800 mg per square meter of body-surface area) was administered alone to a control group [2].
• We conclude that carboplatin is an active agent in advanced endometrial carcinoma and is worthy of further investigation in single-agent and combination chemotherapy [36].
• METHODS: Plasma carboplatin pharmacokinetics determined as ultrafilterable platinum in 70 patients (age range, 23-84 years) treated with different combination regimens that included carboplatin at doses ranging from 184 mg to 950 mg (1-hour intravenous infusion) for various tumor types [3].
• Acute promyelocytic leukaemia after treatment for seminoma with carboplatin [37].

References