PMID- 25601966 OWN - NLM STAT- MEDLINE DCOM- 20151204 LR - 20161215 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 20 IP - 2 DP - 2015 Feb TI - Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis. PG - 111-2 LID - 10.1634/theoncologist.2014-0379 [doi] AB - BACKGROUND: The approved capecitabine regimen as monotherapy in metastatic breast cancer (MBC) is 1,250 mg/m(2) twice daily for 2 weeks on and 1 week off (Cint). Dose modifications are often required because of severe hand-foot syndrome (HFS). We tested a continuous regimen with a lower daily dose but a similar cumulative dose in an attempt to reduce the severity of adverse events (AEs) while maintaining efficacy. METHODS: We randomized 195 patients with HER-2/neu-negative MBC to capecitabine 800 mg/m(2) twice daily throughout the 21-day cycle (Ccont) or to Cint to assess noninferiority in the percentage of patients free of progression at 1 year. Secondary endpoints included efficacy and safety. Associations between polymorphisms in capecitabine metabolism-related genes and drug response were assessed. RESULTS: The percentage of patients free of progression at 1 year was 27.3% with Cint versus 25.3% with Ccont (difference of -2.0%; 95% confidence interval: -15.5% to 11.5%, exceeding the 15% deemed noninferior). Differences regarding other efficacy variables were also not found. Grade 3-4 HFS was the most frequent AE (41.1% in Cint vs. 42.3% in Ccont). Grade 3-4 neutropenia, thrombocytopenia, diarrhea, and stomatitis were more frequent with Cint. A 5' untranslated region polymorphism in the carboxylesterase 2 gene was associated with HFS. One polymorphism in cytidine deaminase and two in thymidine phosphorylase were associated with survival. CONCLUSION: Our study was unable to show noninferiority with the continuous capecitabine regimen (Ccont) compared with the approved intermittent regimen (Cint). Further investigation is required to improve HFS. Polymorphisms in several genes might contribute to interindividual differences in response to capecitabine. CI - (c)AlphaMed Press; the data published online to support this summary is the property of the authors. FAU - Martin, Miguel AU - Martin M AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Universidad Complutense, Madrid, Spain; mmartin@geicam.org. FAU - Martinez, Noelia AU - Martinez N AD - Hospital Universitario Ramon y Cajal, Madrid, Spain; FAU - Ramos, Manuel AU - Ramos M AD - Centro Oncologico Galicia, A Coruna, Spain; FAU - Calvo, Lourdes AU - Calvo L AD - Complejo Hospitalario A Coruna (CHUAC), A Coruna, Spain; FAU - Lluch, Ana AU - Lluch A AD - Hospital Clinico Universitario de Valencia, Valencia, Spain; FAU - Zamora, Pilar AU - Zamora P AD - Hospital Universitario La Paz, Madrid, Spain; FAU - Munoz, Montserrat AU - Munoz M AD - Hospital Clinic de Barcelona, Barcelona, Spain; FAU - Carrasco, Eva AU - Carrasco E AD - GEICAM (Spanish Breast Cancer Group), San Sebastian de los Reyes, Madrid, Spain; FAU - Caballero, Rosalia AU - Caballero R AD - GEICAM (Spanish Breast Cancer Group), San Sebastian de los Reyes, Madrid, Spain; FAU - Garcia-Saenz, Jose Angel AU - Garcia-Saenz JA AD - Hospital Clinico San Carlos, Madrid, Spain; FAU - Guerra, Eva AU - Guerra E AD - Hospital Universitario Ramon y Cajal, Madrid, Spain; FAU - Caronia, Daniela AU - Caronia D AD - Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain; FAU - Casado, Antonio AU - Casado A AD - Hospital Clinico San Carlos, Madrid, Spain; FAU - Ruiz-Borrego, Manuel AU - Ruiz-Borrego M AD - Hospital Universitario Virgen del Rocio, Sevilla, Spain; FAU - Hernando, Blanca AU - Hernando B AD - Hospital General Yague, Burgos, Spain; FAU - Chacon, Jose Ignacio AU - Chacon JI AD - Hospital Virgen de la Salud, Toledo, Spain; FAU - De la Torre-Montero, Julio Cesar AU - De la Torre-Montero JC AD - Hospital Clinico San Carlos, Madrid, Spain; FAU - Jimeno, Maria Angeles AU - Jimeno MA AD - GEICAM (Spanish Breast Cancer Group), San Sebastian de los Reyes, Madrid, Spain; FAU - Heras, Lucia AU - Heras L AD - Hospital General De Hospitalet, Hospitalet de Llobregat, Barcelona, Spain; FAU - Alonso, Rosario AU - Alonso R AD - Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain; FAU - De la Haba, Juan AU - De la Haba J AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC)-Hospital Universitario Reina Sofia, Universidad de Cordoba, Cordoba, Spain; FAU - Pita, Guillermo AU - Pita G AD - Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain; FAU - Constenla, Manuel AU - Constenla M AD - Complejo Hospitalario de Pontevedra, Pontevedra, Spain. FAU - Gonzalez-Neira, Anna AU - Gonzalez-Neira A AD - Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain; LA - eng SI - ClinicalTrials.gov/NCT00418028 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20150119 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 6804DJ8Z9U (Capecitabine) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Breast Neoplasms/*drug therapy/genetics/pathology MH - Capecitabine/*administration & dosage/adverse effects MH - Disease-Free Survival MH - Drug Administration Schedule MH - Female MH - Fluorouracil/administration & dosage MH - Hand-Foot Syndrome/etiology/*pathology MH - Humans MH - Middle Aged MH - *Pharmacogenetics MH - Treatment Outcome PMC - PMC4319639 EDAT- 2015/01/21 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/01/19 CRDT- 2015/01/21 06:00 PHST- 2015/01/21 06:00 [entrez] PHST- 2015/01/21 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/01/19 00:00 [pmc-release] AID - theoncologist.2014-0379 [pii] AID - T14379 [pii] AID - 10.1634/theoncologist.2014-0379 [doi] PST - ppublish SO - Oncologist. 2015 Feb;20(2):111-2. doi: 10.1634/theoncologist.2014-0379. Epub 2015 Jan 19.