Document Detail


In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma.
MedLine Citation:
PMID:  8490836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cisplatin and its analogue carboplatin have been shown to cause dose-dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR-3, 2780, HTB-77, and CRL-1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less-than-synergistic effect, as was revealed by an isobologram in the OVCAR-3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum-sensitive tumors. METHODS: In a Phase II study, the efficacy, the toxicity profile, and the feasibility of combining both substances were assessed in 20 previously untreated patients with ovarian cancer. The regimen consisted of carboplatin (300 mg/m2) on day 1, followed by cisplatin (100 mg/m2) on day 2 every 4 weeks. RESULTS: A total of 81 cycles were administered (median, 4 cycles; range, 1-6 cycles); four patients experienced complete remission and three experienced clinical partial remissions. Limiting toxicities were thrombocytopenia, leukopenia, and ototoxicity. The mean (+/- standard deviation [SD]) carboplatin and cisplatin dose intensities (DI) reached during the first four cycles of therapy were 58 mg/m2/week (+/- 18 mg/m2/week) and 21 mg/m2/week (+/- 7 mg/m2/week), respectively, which corresponded closely to the projected DI of 75 and 25 mg/m2/week, respectively. Based on the equivalence ratio of 4:1, the DI of carboplatin has been converted into the respective cisplatin DI, resulting in a total DI estimate. The overall DI of 37 mg/m2/week (+/- 14 mg/m2/week) was close to the projected one of 44 mg/m2/week. CONCLUSIONS: Combining cisplatin with carboplatin was found to represent a feasible and efficacious therapeutic strategy for increasing platinum dose intensity.
Authors:
C Dittrich; P Sevelda; M Baur; C Marth; M Hudec; N Vavra; T Grunt; B Fazeny; H Salzer
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Cancer     Volume:  71     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  1993 May 
Date Detail:
Created Date:  1993-06-15     Completed Date:  1993-06-15     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3082-90     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine I, University of Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Anemia / chemically induced
Antineoplastic Combined Chemotherapy Protocols
Carboplatin / administration & dosage*,  adverse effects,  pharmacokinetics
Cisplatin / administration & dosage*,  adverse effects,  pharmacokinetics
Dose-Response Relationship, Drug
Female
Humans
Leukocyte Count / drug effects
Ovarian Neoplasms / drug therapy*
Pilot Projects
Platelet Count / drug effects
Platinum / metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
15663-27-1/Cisplatin; 41575-94-4/Carboplatin; 7440-06-4/Platinum

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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