Toxicities of the platinum antineoplastic agents

Markman, Maurie

doi:10.1517/14740338.2.6.597

Cited by 122 publications

(34 citation statements)

References 95 publications

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“…It is also likely that most of the hypersensitivity reactions may have been due to the carboplatin, a phenomenon that is well recognized in a pretreated population (29). Of the four patients who developed a grade 3 hypersensitivity reaction, treatment was stopped in two patients and was successfully continued for several further cycles in the other two patients, with the administration of appropriate premedication.…”

Section: Resultsmentioning

confidence: 99%

A Phase Ib and Pharmacokinetic Trial of Patupilone Combined with Carboplatin in Patients with Advanced Cancer

Förster

Kaye

Oza

et al. 2007

Clinical Cancer Research

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Purpose: Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/resistant tumor types. The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors. Experimental Design: Patients with advanced cancer received patupilone via a 5-to 10-min i.v. infusion at doses of 3.6 to 6.0 mg/m 2 q3w, immediately followed by carboplatin area under the curve (AUC) 5 or 6 mg/mL/min. Results: Of the 37 patients enrolled, the majority previously received taxanes (81%) and/or platinum-containing drugs (97.3%). The maximum tolerated dose (MTD) of patupilone with carboplatin AUC 6 was 4.8 mg/m 2 ; additional patients were enrolled to consolidate experience at this dose. Of the 22 patients who received the MTD, the most common nonhematologic adverse events were fatigue in six (27.3%) and diarrhea, nausea, vomiting, abdominal pain, and neuropathy in one each (4.5%; all grade 3); hematologic toxicities included two patients (9.1%) with grade 3 neutropenia. The pharmacokinetics of patupilone were similar to those in a previous study of patupilone monotherapy. Of the 26 patients with recurrent platinum-sensitive ovarian cancer, tumor response was assessable by response evaluation criteria in solid tumors in 17; 1 patient (6%) achieved a complete response, and 10 (59%) achieved a partial response. Conclusions: The combination of patupilone 4.8 mg/m 2 /carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinumsensitive ovarian cancer. The optimal dose for this regimen is currently being further refined in phase II trials.

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Section: Resultsmentioning

confidence: 99%

A Phase Ib and Pharmacokinetic Trial of Patupilone Combined with Carboplatin in Patients with Advanced Cancer

Förster

Kaye

Oza

et al. 2007

Clinical Cancer Research

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“…All reactions were carried out with dry and freshly distilled solvents. Column chromatography refers to flash chromatography and was carried out on SiO 2 (13); N(1)\C(1),1.339 (6); N(1)\N(2), 1.370 (6); N(3)\C(7), 1.499 (5); N(3)\C(6), 1.499 (7); N(3)\C(8), 1.506(6); C(1)\C(2), 1.409(8); C (2)\C(3), 1.367(10); C(3)\N(2), 1.349 (7); N(2)\C(5), 1.453(7); C(5)\C(6), 1.483 (7); N (1)\Pt\N(3), 93.57 (15); N(1)\Pt\Cl(1), 176.60 (11), N(3)\Pt\Cl(1), 89.61 (12); N (1)\Pt\Cl(2), 89.32 (12) ). (from 2% to 5%)} to yield 28 mg ( …”

Section: Methodsmentioning

confidence: 99%

Platinum(II) and palladium(II) complexes with (N,N′) and (C,N,N′)− ligands derived from pyrazole as anticancer and antimalarial agents: Synthesis, characterization and in vitro activities

Quirante

Ruíz

González

et al. 2011

Journal of Inorganic Biochemistry

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The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH 2 ) 2 NMe 2 }-3,5-R 2 -pzol] {where pzol represents pyrazole and R_H (1a), Me (1b) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC 50 = 3 μM) versus breast cancer cell lines (IC 50 N 20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.

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“…However, cisplatin displays, along with other kinds of anticancer drugs, two major drawbacks: (a) severe toxicities (neurotoxicity, nephrotoxicity, etc.) and (b) limited applicability to a narrow range of tumors, as several of them exhibit natural or induced resistance (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

A Ruthenium-Containing Organometallic Compound Reduces Tumor Growth through Induction of the Endoplasmic Reticulum Stress GeneCHOP

et al. 2009

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Cisplatin-derived anticancer therapy has been used for three decades despite its side effects. Other types of organometallic complexes, namely, some ruthenium-derived compounds (RDC), which would display cytotoxicity through different modes of action, might represent alternative therapeutic agents. We have studied both in vitro and in vivo the biological properties of RDC11, one of the most active compounds of a new class of RDCs that contain a covalent bond between the ruthenium atom and a carbon. We showed that RDC11 inhibited the growth of various tumors implanted in mice more efficiently than cisplatin. Importantly, in striking contrast with cisplatin, RDC11 did not cause severe side effects on the liver, kidneys, or the neuronal sensory system. We analyzed the mode of action of RDC11 and showed that RDC11 interacted poorly with DNA and induced only limited DNA damages compared with cisplatin, suggesting alternative transduction pathways.

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Toxicities of the platinum antineoplastic agents

Cited by 122 publications

References 95 publications

A Phase Ib and Pharmacokinetic Trial of Patupilone Combined with Carboplatin in Patients with Advanced Cancer

A Phase Ib and Pharmacokinetic Trial of Patupilone Combined with Carboplatin in Patients with Advanced Cancer

Platinum(II) and palladium(II) complexes with (N,N′) and (C,N,N′)− ligands derived from pyrazole as anticancer and antimalarial agents: Synthesis, characterization and in vitro activities

A Ruthenium-Containing Organometallic Compound Reduces Tumor Growth through Induction of the Endoplasmic Reticulum Stress GeneCHOP

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