RGD Reference Report - Phase II studies of gemcitabine and cisplatin in heavily and minimally pretreated metastatic breast cancer. - Rat Genome Database

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Phase II studies of gemcitabine and cisplatin in heavily and minimally pretreated metastatic breast cancer.

Authors: Chew, HK  Doroshow, JH  Frankel, P  Margolin, KA  Somlo, G  Lenz, HJ  Gordon, M  Zhang, W  Yang, D  Russell, C  Spicer, D  Synold, T  Bayer, R  Hantel, A  Stiff, PJ  Tetef, ML  Gandara, DR  Albain, KS 
Citation: Chew HK, etal., J Clin Oncol. 2009 May 1;27(13):2163-9. doi: 10.1200/JCO.2008.17.4839. Epub 2009 Mar 23.
RGD ID: 11340203
Pubmed: PMID:19307510   (View Abstract at PubMed)
PMCID: PMC2674003   (View Article at PubMed Central)
DOI: DOI:10.1200/JCO.2008.17.4839   (Journal Full-text)

PURPOSE: Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. PATIENTS AND METHODS: Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m(2) on days 1 through 4 and gemcitabine 1,000 mg/m(2) on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. RESULTS: Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor-negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)-751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. CONCLUSION: Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast Neoplasms disease_progressionIAGP 11340203DNA:SNP:exon:p.K751Q (rs13181) (human)RGD 
Breast Neoplasms disease_progressionISOERCC2 (Homo sapiens)11340203; 11340203DNA:SNP:exon:p.K751Q (rs13181) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ercc2  (ERCC excision repair 2, TFIIH core complex helicase subunit)

Genes (Mus musculus)
Ercc2  (excision repair cross-complementing rodent repair deficiency, complementation group 2)

Genes (Homo sapiens)
ERCC2  (ERCC excision repair 2, TFIIH core complex helicase subunit)


Additional Information