Carbo-platin

Neijt IP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carbo-platin in advanced ovarian cancer. J Clin Oncol 2000 18 3084-3092. 

Ramsey SD, Moinpour CM, Lovato LC, Crowley JJ, Grevstad P, Presant CA et al. Economic analysis of vi-norelbine plus cisplatin versus paclitaxel plus carbo-platin for advanced non-small-cell lung cancer. J Natl Cancer Inst 2002 94 291-7. 

Gergel D, Misik V, Ondrias K (1992) Effect of cisplatin, carbo-platin and stobadine on lipid peroxidation of kidney homogenate and phosphatidylcholine liposomes. Physiol Res 41 129-134... 

The nenrotoxicity of platinnm-containing componnds has been reviewed (56,57), as has the prevention of cisplatin-associated nenrotoxicity (58). In experimental measnre-ments of sensory nerve condnction velocity oxaliplatin cansed the most impairment, followed by cisplatin, carbo-platin, and satraplatin (JM216) (59). The cumnlative incidence of grade 2 peripheral sensory neuropathy with oxaliplatin was 19% (60). 

Ocular effects, including optic neuritis, papilledema, and retrobulbar neuritis, are uncommon adverse effects of cisplatin-containing cancer chemotherapy. The risk of retinal toxicity is restricted to high-dose cisplatin therapy (for example 200 mg/m over 5 days) and can result in blurred vision and altered color perception, which can persist for several months. In contrast to cisplatin, carbo-platin is seldom involved in drug-induced visual disturbances. In two cases there was a relation between the administration of carboplatin (800-1200 mg/m ) and the occurrence of chnical cortical blindness (122). However, both patients had impaired renal function before the start of therapy with carboplatin. 

The use of 20 80 CPP SA and 18 82 FAD SA copolymers disks as drug delivery devices for carbo-platin, a treatment for glioma, was also investigated in rodents.The majority of the drug was released in seven days from the CPP SA copolymer disk, and 65% of the drug was released from the FAD SA copolymer disk in seven days. This method of delivery was more effective than systemic therapy and did not cause systemic toxicity. 

The combination regimen of paclitaxel (or docetaxel) and carbo-platin frequently is responsible for producing hypersensitivity reactions. Each agent precipitates a distinct reaction, allowing for differentiation between causative factors. Hypersensitivity reactions have been observed with paclitaxel and docetaxel as frequently as 34% of... 

Elferink F, van der Viigh WJF, Klein I, et al. Pharmacokinetics of carbo-platin after intraperitoneal administration. Cancer Chemother Pharmacol 1988 21 57-60. 

Figure 2.12 DNA crosslinking. The deleterious properties of nitrogen mustards are explained through the illustrated interstrand linkage mechanism that makes DNA impossible to duplicate or transcribe. Intrastrand crosslinking is the basis of action for anti-cancer drugs such as c/s-platin and carbo-platin. This is intended to prevent DNA duplication and hence cancer cell division. DNA crosslinking to proteins (such as histones) uses a non-covalent DNA intercalator with two azide functional groups. Both azides are activated for covalent coupling under photo-chemical conditions so that DNA subsequently becomes covalently linked to protein.

Kobayashi H, Eckhardt S G, et al. (2005). Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGER-1 ribozyme, in combination with carbo-platin and paclitaxel in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 56 329-336. 

Avastin was studied in NSCLC and approved in 2006 for NSCLC treatment in combination with carbo-platin and paclitaxel for the initial systemic treatment of patients with unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer. An improvement in survival time was reported when Avastin was added to a standard chemotherapy regimen. A multi-center clinical trial supporting this approval enrolled 878 patients who had not received prior chemotherapy (Sandler et al. 2006). The trial compared the effectiveness of Avastin plus carboplatin and pacUtaxel with chemotherapy by carboplatin and paclitaxel alone. The median overall survival time for patients in the Avastin plus carboplatin and pacUtaxel arm was 12.3 vs 10.3 months for patients receiving only carboplatin and paclitaxel. 

Further studies are needed to determine the risks in patienb with predbposing cardiac risk factors who are being treated with paclitaxel. A retrospective review of patienb with major cardiac risk factors who were treated with paclitaxel (either monotherapy or in combination with cbplatin or carbo-platin) did not find any evidence of reduced cardiac function after treatment with paclitaxel. However the series only consbted of 15 patients [36 ]. 

Kelly, K., Crowley, J., Bunn, PA., etal. (2001). Randomized phase III trial of paclitaxel plus carbo-platin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer A southwest oncology group trial. J. Clin. Oncol. 19. 3210-3218. 

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