Academic Journal
Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer
| العنوان: | Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer |
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| المؤلفون: | Ledermann, Jonathan A., Gabra, Hani, Jayson, Gordon C., Spanswick, Victoria J., Rustin, Gordon J S, Jitlal, Mark, James, Lindsay E., Hartley, John A. |
| المصدر: | Ledermann , J A , Gabra , H , Jayson , G C , Spanswick , V J , Rustin , G J S , Jitlal , M , James , L E & Hartley , J A 2010 , ' Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer ' , Clinical Cancer Research , vol. 16 , no. 19 , pp. 4899-4905 . https://doi.org/10.1158/1078-0432.CCR-10-0832 |
| سنة النشر: | 2010 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| الوصف: | Background: The potential of gemcitabine to interact with carboplatin was explored in a phase II trial in platinum-resistant ovarian cancer. Peripheral blood lymphocytes were sampled after drug administration to measure DNA interstrand cross-link formation and repair. Patients and Methods: Forty patients received carboplatin target area under concentration-time curve (AUC 4) followed by gemcitabine 1,000 mg/m2 with a second dose of gemcitabine on day 8. Peripheral blood lymphocytes were obtained in 12 patients before and at intervals during the first cycle of chemotherapy. DNA cross-link formation and repair (unhooking) were measured by the single-cell gel electrophoresis (comet) assay following ex vivo incubation. Results: The global response rate was 47% (Response Evaluation Criteria in Solid Tumors rate, 29%; CA125 rate, 63%). Delays in treatment were seen in 24% of cycles largely due to myelosuppression; 15% of day 8 administration was omitted. Peak carboplatin-induced DNA cross-linking was seen by 24 hours. Significant reduction was seen in the repair of in vivo carboplatin-induced DNA cross-links following administration of gemcitabine. Conclusion: An enhanced activity of carboplatin in platinum-resistant ovarian cancer may be due to synergy with gemcitabine through inhibition of repair of DNA cross-links. Future studies should explore coadministration of these drugs, as this may be a more effective schedule. ©2010 AACR. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1158/1078-0432.CCR-10-0832 |
| الاتاحة: | https://research.manchester.ac.uk/en/publications/867e4343-9a95-486f-8e34-fa6358894457 https://doi.org/10.1158/1078-0432.CCR-10-0832 http://clincancerres.aacrjournals.org/content/16/19/4899.full.pdf+html |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.CE4DF774 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/1078-0432.CCR-10-0832 |
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