Disposition of Cisplatin vs Total Platinum in Animals and Man

1984 ◽  
pp. 126-147 ◽  
Author(s):  
L. A. Sternson ◽  
A. J. Repta ◽  
H. Shih ◽  
K. J. Himmelstein ◽  
T. F. Patton
Keyword(s):  
Total Platinum

scholarly journals Geochemistry of the Madawara Igneous Complex, Bundelkhand Craton, Central India: Implications for PGE Metallogeny

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Satyanarayanan Manavalan ◽  
Surya Prakash Singh ◽  
Vysetti Balaram ◽  
Mohanty Niranjan
Keyword(s):  
Central India ◽  
Shear Zones ◽  
Ultramafic Rocks ◽  
Spinel Peridotite ◽  
Igneous Complex ◽  
Total Platinum ◽  
Group I ◽  
Ultramafic Complex ◽  
Group Ii ◽  
High Degree

Abstract The southern part of the Bundelkhand craton contains a series of a E-W trending mafic and ultramafic rocks, about 40 km in length and 2–4 km wide, that occur as intrusions within the Bundelkhand Gneissic Complex (BnGC). They are confined between the Madawara- Karitoran and Sonrai-Girar shear zones. Dunite, harzburgite, lherzolite and websterite are the commonly occurring ultramafic rocks that have high MgO, Ni, Cr, PGE and low Al2O3, CaO, K2O, TiO2 and V contents, and shows peridotitic affinity. A distinct trend of crystallization from peridotite to komatiitic basalt has been inferred from geochemical plots, which also indicates the occurrence of at least two varieties among the ultramafic suite of the Madawara ultramafic complex, namely, Group I comprising dunite, spinel peridotite, harzburgite and lherzolite, and Group II consisting of pyroxenite, websterite and olivine websterite. In several places, the rocks of Group II have an intrusive relationship with Group I, and are relatively enriched in total platinum group elements (PGE ~ 300 ppb). The discrimination diagrams suggest that the PGE are enriched in low sulphur-fugacity source magma at moderate to deeper depths by high degree of partial melting of the mantle.

Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin

1986 ◽  
Vol 39 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Jan B Vermorken ◽  
Wim J F Van Der Vijgh ◽  
Ina Klein, Helen E Gall ◽  
Cees J Van Groeningen ◽  
Guus A M Hart ◽  
...  
Keyword(s):  
Total Platinum ◽  
Platinum Species

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin

1992 ◽  
Vol 29 (5) ◽  
pp. 385-390 ◽  
Author(s):  
R. Leone ◽  
M. E. Fracasso ◽  
E. Soresi ◽  
G. Cimino ◽  
M. Tedeschi ◽  
...  
Keyword(s):  
Total Platinum

Phase I study of combination chemotherapy consisting of capecitabine plus fractional cisplatin for unresectable gastric cancer in an outpatient setting.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 173-173
Author(s):  
Tsunehiro Takahashi ◽  
Yoshiro Saikawa ◽  
Kazumasa Fukuda ◽  
Rieko Nakamura ◽  
Norihito Wada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Combination Chemotherapy ◽  
Outpatient Setting ◽  
High Dose ◽  
Standard Regimen ◽  
Total Platinum ◽  
Adequate Hydration ◽  
Level 3 ◽  
Unresectable Gastric Cancer

173 Background: The combination chemotherapy of capecitabine and cisplatin is one of the standard regimen for unresectable gastric cancer. However, the high dose of cisplatin could cause the nephrotoxicity and require the adequate hydration to avoid the damage of renal during the administration. For that reason, the hospitalization is recommended for the patients to receive the chemotherapy including high dose of cisplatin. The present study aimed to establish the proper dose of fractional cisplatin in the combination with capecitabine in an outpatient setting. Methods: Capecitabine was administered orally every day from the evening of day 1 to the morning of 15. Cisplatin were infused on days 1, 8 and 15 for 60 minutes without hydration. The starting dose of cisplatin was 15 mg/m2 as level 1. The following cisplatin dose could be given to subsequent cohorts of patients depending on safety findings observed in the previous cohort: level 2, 20 mg/m2 and level 3, 25 mg/m2, respectively. Serum concentration of total platinum was analyzed before the administration of cisplatin on days 1, 8 and 15. Results: A total of 9 patients were recruited. The median age was 64 years and there were 8 males and one female. Histological types included intestinal (n=5) and diffuse (n=4). Eight patients had multiple metastatic sites, including lymph nodes (n=8), peritoneum (n=5), liver (n=3), lung (n=2) and bone (n=1). The major toxicities were thrombocytopenia (67%), leukopenia (56%) and neutropenia (22%). However, no dose-limiting toxicity was observed in each level. Therefore, the recommended dose of cisplatin was 25 mg/m2. Of the 9 patients, 6 patients had measurable lesions and 5 patients had partial responses, resulting in an overall response rate of 83%. The median administered course was four. In patients at level 3, the mean concentration of total platinum on days 8 and 15 were 0.25μg/ml and 0.42μg/ml, respectively. Conclusions: The recommend dose of cisplatin was confirmed with 25 mg/m2 weekly. Although its safety and feasibility should be evaluated in further clinical trial, this regimen could be expected as an outpatient treatment for unresectable gastric cancer. Clinical trial information: 000005708.

Continuous infusion of high-dose cisplatin in children: Pharmacokinetics of free and total platinum

1987 ◽  
Vol 23 (11) ◽  
pp. 1649-1652 ◽  
Author(s):  
Martine Bues-Charbit ◽  
Jean-Claude Gentet ◽  
Jean-Louis Bernard ◽  
Valentine Breant ◽  
Jean-Paul Cano ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
High Dose ◽  
Total Platinum

Cisplatin-Induced Ototoxicity and Pharmacokinetics: Preliminary Findings in a Dog Model

2002 ◽  
Vol 111 (8) ◽  
pp. 745-750 ◽  
Author(s):  
Ravi Sockalingam ◽  
Bruce Charles ◽  
Lucio Filippich ◽  
Bruce Murdoch
Keyword(s):  
Otoacoustic Emissions ◽  
Plasma Concentrations ◽  
Distortion Product Otoacoustic Emissions ◽  
High Dose ◽  
Clinical Dose ◽  
Distortion Product ◽  
Total Platinum ◽  
Dog Model ◽  
Early Effects ◽  
The Relationship

The early effects of a clinical dose of cisplatin (100 mg/m2) on distortion-product otoacoustic emissions (DPOAE) thresholds and the relationship between DPOAE threshold shifts and changes in plasma concentrations of filterable and total platinum (Pt) following infusion of cisplatin in a dog model were investigated. The DPOAE thresholds (based on input-output function) were measured 2 days before a single high dose of cisplatin administration, and compared with measurements recorded 2 and 4 days after infusion. The results revealed DPOAE thresholds to be elevated by 4 days after the administration of cisplatin. However, this elevation could not be correlated with plasma concentrations of filterable and total Pt, which showed little variation over the 48-hour postinfusion period between animals. The present study demonstrated that DPOAE thresholds have the potential to be used as an indicator of cisplatin-induced ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma Pt kinetics in individual animals.

A phase I trial of isolated hepatic perfusion (IHP) using 5-FU and oxaliplatin in patients with unresectable isolated liver metastases (ILM) from colorectal cancer (CRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 283-283
Author(s):  
Deepa Magge ◽  
Amer H Zureikat ◽  
David L. Bartlett ◽  
Matthew Peter Holtzman ◽  
Haroon Choudry ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Systemic Exposure ◽  
Fixed Dose ◽  
Dose Escalation Study ◽  
Total Platinum ◽  
Isolated Hepatic Perfusion ◽  
Prospective Phase ◽  
Grade 3

283 Background: IHP is a proven approach for regional delivery of chemotherapy in patients with unresectable ILM. This study sought to determine safety and MTD of administering 5FU in combination with fixed dose oxaliplatin via IHP. Methods: Prospective Phase I dose escalation with standard 3x3 dosing. Subjects with unresectable ILM from CRC scheduled to receive an HAI pump were eligible. IHP employed fixed dose oxaliplatin (previously established)with escalating doses of 5FU. 1 endpoint was to determine MTD for this combination. 2 endpoints were response to IHP alone, PFS, and OS for IHP + HAI-FUDR. Systemic and IHP plasma PK of 5FU, anabolites, total, and free platinum were determined by validated assays. Results: Between Aug 2007 - Mar 2011, 11 subjects were enrolled. All patients received at least one line of pre-IHP systemic chemotherapy. There were 4 Grade 3 SAE (36.3%) and no grade 4 events. 2 DLTs occurred in the second dose cohort of 300mg/m2. Dose escalation was terminated and 200mg/m2 5FU was determined to be the MTD. There was 1 DLT in the dose de-escalating phase of 200mg/m2. At first follow-up, 9 pts (82%) had a partial response, while 2 (18%) had stable disease. 64% of pts had a >50% decrease in CEA level. Actuarial 1 and 2 year survival was 100% and 75% respectively, with median follow-up of 23 mos. IHP exposures (AUC0-60min) were 10.9±4.5 µgPt·h/mL (platinum), 49.3±30.7 µg·h/mL 5FU (DL1) and 70.5±35.5 µg·h/mL 5FU (DL2). Free platinum represented 82±14% of total platinum. Systemic exposure (AUC0-inf) relative to IHP exposure was negligible for both total platinum (1.1±1.5%) and 5FU (0.09±0.10%). IHP exposure to metabolites relative to 5FU was 4.9±2.5% for FUrd and 0.23±0.14% for FdUrd, respectively. Conclusions: MTD for IHP with 5FU and oxaliplatin is 200 mg/m2 and 40mg/m2 respectively. Systemic exposure to the agents was minimal. The response and survival observed in this dose escalation study warrants assessment in a larger phase II trial. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document