Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Platinum Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1979

Schedule-dependency assessments of ribonucleoside diphosphate reductase inhibitors when used in combination with platinum compounds plus cyclophosphamide in the treatment of advanced L1210 leukemia.

Each of three ribonucleoside diphosphate reductase inhibitors was used as a third drug in combination with selected antitumor platinum (Pt) agents and cyclophosphamide (CY) in the treatment of advanced L1210 leukemia in C57BL/6 x DBA/2 mice. Each was synergistic with the various Pt plus CY combinations but the effect was highly schedule dependent. The collective cure rate was 68% when hydroxyurea (HU) was given as a single injection with Pt plus CY; the cure rate was 15% when HU was administered on a divided-dose schedule with Pt plus CY. The collective cure rate was 53% when guanazole was given as a single injection with Pt plus CY, but was only 8% when it was given on a divided-dose schedule with Pt plus CY. The effect of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, when used as a third drug with the various Pt plus CY regimens, was not schedule dependent as assessed by the collective cure rate. A therapeutic synergy between CY and each of the three ribonucleoside diphosphate reductase inhibitors was also observed.

Animals↗
PubMed2006

1,2-GG intrastrand cross-link of antitumor dinuclear bifunctional platinum compound with spermidine linker inhibits DNA polymerization more effectively than the cross-link of conventional cisplatin.

In order to learn more about the molecular basis for the inhibition of DNA replication produced by antitumor platinum drugs, we investigated DNA polymerization using DNA templates site-specifically modified with the 1,2-GG intrastrand cross-link of dinuclear bifunctional [{trans-PtCl(NH(3))(2)}(2){l-spermidine-N1,N8}](3+)(BBR3571) or conventional mononuclear cisplatin. These cross-links which have the same nature, but differ in the size and character of the conformational alteration induced in double-helical DNA, were analyzed for bypass ability with reverse transcriptase of human immunodeficiency virus type 1 and Klenow fragment of DNA polymerase I deficient in exonuclease activity. We found that the 1,2-GG intrastrand CL of BBR3571 inhibited DNA translesion synthesis markedly more than the same adduct of cisplatin. This result was explained by a larger size of the cross-link of BBR3571 and by a flexibility induced in DNA by this cross-link which can make the productive binding of this adduct at the polymerase site more difficult.

Antineoplastic Agents↗
PubMedDate not supplied

Antitumor activity of a new platinum compound (glycolate-o,o') diammineplatinum (II) (254-S), against non-small cell lung carcinoma grown in a human tumor clonogenic assay system.

(Glycolate-o,o') diammineplatinum (II) (254-S) is one of the platinum derivatives showing high activity against rodent solid tumors and lack of renal toxicity. We have used a human tumor clonogenic assay (HTCA) as a disease-oriented drug screening model for new antitumor drugs, in order to test the antitumor activity of 254-S against non-small cell lung carcinoma (NSCLC) and to compare its activity with that of cisplatin (CDDP) and of carboplatin (CBDCA). The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 254-S was observed in 10/29 and 20/30 evaluable specimens isolated freshly from NSCLC patients with continuous exposure at 1 and 10 micrograms/ml, respectively, indicating a positive dose-response relationship. Dose dependent cytotoxicity was also confirmed in 4 human tumor cell lines derived from NSCLC patients. The antitumor activity of 254-S was 3.6-fold that of CBDCA, but two-fifths that of CDDP. A comparison of these in vitro results with the toxic properties of 254-S such as low nephrotoxicity suggests that 254-S is a promising new drug against NSCLC.

Antineoplastic Agents↗
PubMed2004

Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials.

BACKGROUND: Single new agents reportedly produce promising response and survival effects, but platinum-based doublets remain the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the effectiveness of platinum for advanced NSCLC by carrying out a meta-analysis of trials that compared platinum-based doublets with single new agent therapy alone. METHODS: We carried out a literature search to identify trials, conducted between 1994 and 2003, comparing a doublet of platinum plus a new agent with a new agent alone in previously untreated patients with advanced NSCLC. Outcomes analysed were response, survival and toxicity. RESULTS: Eight trials encompassing 2374 patients were identified. Platinum-based doublets produced an approximately two-fold higher overall (complete and partial) response rate than the new agent alone [odds ratio = 2.32; 95% confidence interval (CI)=1.68-3.20]. Platinum-based doublet therapy was also associated with a 13% prolongation of survival (hazard ratio = 0.87; 95% CI = 0.80-0.94, P <0.001). Despite significant increases in the frequencies of various toxic effects in patients receiving platinum-based doublets, no significant difference in treatment-related mortality was observed. CONCLUSION: This is the first published meta-analysis demonstrating the importance of combining platinum with single new agents in the treatment of advanced NSCLC.

Antineoplastic Agents↗
PubMedDate not supplied

Pharmacokinetics of a new platinum compound, cis-(glycolato-O,O) [(4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclohexane]plat inum (II) in dogs.

A pharmacokinetic study on cis-(glycolato-O,O)/ (4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'- cyclohexane]platinum(II) (SKI 2032R) was performed in dogs. A single dose of 2.0 mg/kg of SKI 2032R was administered i.v. bolus to three beagle dogs. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for SKI 2032R declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0 --> infinity) determined for ultrafiltrable platinum derived from SKI 2032R, as an active component, was 2.36 +/- 0.23 micrograms. h/ml (mean +/- S.D.), with an initial half-life of 0.23 +/- 0.20 hour, a terminal half-life of 1.32 +/- 0.49 hour, a total clearance of 14.17 +/- 1.50 ml/min/kg, and a steady-state volume of distribution of 1.21 +/- 0.24 l/kg.

Animals↗
PubMed1999

Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma.

Based on previous clinical experience indicating the tolerability and efficacy of high-dose cisplatin with glutathione protection in the treatment of advanced ovarian cancer, this study was undertaken to explore the efficacy and feasibility of an alternative high-dose, platinum-based approach including a combination of high-dose cisplatin plus carboplatin as induction chemotherapy of advanced ovarian carcinoma and intervention surgery. Fifty consecutive eligible patients with untreated stage III or IV epithelial ovarian cancer received 40 mg/m(2) cisplatin daily on days 1-4 and 160 mg/m(2) carboplatin on day 5. The cycle was repeated after 28 days. Patients received glutathione (2,500 mg) before each cisplatin or carboplatin administration and standard intravenous hydration. After 2 courses of induction chemotherapy, the patients underwent surgical reevaluation with debulking, when possible, followed by a further 3 cycles of 120 mg/m(2) cisplatin (i.e. 40 mg/m(2) daily for 3 consecutive days plus 600 mg/m(2) cyclophosphamide on day 3) except in instances of lack of response. All eligible patients were assessed for response and toxicity. The toxicity was moderate with lack of significant nephrotoxicity. Neurotoxicity and ototoxicity were acceptable and in no patient was treatment discontinued for those toxic effects. Myelotoxicity was somewhat more severe than that observed with our previous study with high-dose cisplatin and probably related to the addition of carboplatin. Of the 40 responsive patients, 23 (46%) had a pathological complete response and 4 (8%) had a clinical complete response (without second-look laparotomy). The efficacy of the present protocol was also documented by overall survival (median survival >48 months), which appeared to be better than expected with the current therapy in this group with advanced/bulky disease. The impressive efficacy suggests a possible contribution of reduced glutathione itself in improving the outcome, as supported by preclinical studies. The results of this study should be placed in context with current platinum-based therapy including paclitaxel.

Adult↗
PubMedDate not supplied

Induction of DNA-protein cross-links by platinum compounds.

The differences between cis- and trans-diamminedichloroplatinum II (DDP) in forming DNA-protein cross-links in isolated human lymphocytes were investigated. Both cis- and trans-DDP can induce DNA-protein cross-links. We show that cis-DDP forms complexes between DNA and proteins faster than trans-DDP. This results from an increase in the quantity of DNA and platinum together with an increase in drug concentration. Under the same conditions trans-DDP causes a decrease in DNA-forming complexes with proteins. After a 12 h incubation of lymphocytes we observe a similar level of DNA in DNA-protein cross-links induced by DDP isomers, but more platinum appears in complexes induced by trans-DDP. The results obtained demonstrate that the antitumor drug - cis-DDP and the clinically ineffective trans-DDP induce links between DNA and proteins in a different manner. We suggest that the therapeutic activity of cis-DDP can in part arise from rapidly forming DNA-protein complexes which can destroy the most important cellular processes, such as replication and transcription.

Blood Proteins↗
PubMed1992

Meta-analysis of the role of platinum compounds in advanced ovarian carcinoma. The Advanced Ovarian Cancer Trialists Group.

This paper presents a systematic overview or meta-analysis of 54 randomized clinical trials testing a variety of chemotherapeutic approaches in advanced ovarian carcinoma. Prolonged follow-up data are available for most patients and individual patient data were made available for all patients; analysis was made on the basis of "intention to treat." Our report concentrates on two comparisons: (1) platinum alone versus platinum in combination, which appears to show a long-term survival advantage for the combination (however, the platinum dose in the single-agent arm was relatively low); and (2) carboplatin versus cisplatin, which shows no obvious survival differences. It is striking that no single study to date has been large enough to detect the modest survival differences expected from current therapy. Consequently, a series of international studies have been initiated. The International Collaborative Ovarian Neoplasm (ICON) group will examine the role of adjuvant chemotherapy in early ovarian cancer (ICON 1) and will compare carboplatin with cisplatin, doxorubicin, and cyclophosphamide in more advanced disease (ICON 2).

Antineoplastic Combined Chemotherapy Protocols↗