PMID- 23860530 OWN - NLM STAT- MEDLINE DA - 20130821 DCOM- 20131104 IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 109 IP - 4 DP - 2013 Aug 20 TI - A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. PG - 859-65 LID - 10.1038/bjc.2013.400 [doi] AB - BACKGROUND: We evaluated the efficacy of aprepitant plus granisetron and an increased dose of dexamethasone in selected patients undergoing moderately emetogenic chemotherapy (MEC). METHODS: Nondrinking women <70 years undergoing MEC were randomly assigned to aprepitant (day 1, 125 mg; days 2 and 3, 80 mg) or placebo. Dexamethasone on days 1-3 was 12, 4, and 4 mg with aprepitant and 20, 8, and 8 mg with placebo. The primary end point was complete response (CR; no emesis or rescue therapy) during 120 h of the first cycle. Logistic regression analysis was performed to identify predictors of overall CR. RESULTS: Of the 94 patients enrolled, 91 were assessable. Most received carboplatin-based chemotherapy. In the aprepitant (n=45) and placebo (n=46) groups, the overall, acute (day 1), and delayed (days 2-5) CR rates were 62% and 52%, 98% and 96%, and 62% and 52%, respectively. Although not statistically significant, the overall CR rate was 10% higher in the aprepitant group. Both regimens were well tolerated. On multivariate analysis, advanced ovarian cancer (OR, 0.26 (0.10-0.72)) was independently associated with a lower CR. CONCLUSION: Even with an increased dose of dexamethasone, aprepitant seemed more effective than placebo in these selected patients undergoing MEC; however, delayed phase management remains a significant problem. AD - Medical Oncology, Hyogo Cancer Center, Akashi, Japan. tanioka@hp.pref.hyogo.jp FAU - Tanioka, M AU - Tanioka M FAU - Kitao, A AU - Kitao A FAU - Matsumoto, K AU - Matsumoto K FAU - Shibata, N AU - Shibata N FAU - Yamaguchi, S AU - Yamaguchi S FAU - Fujiwara, K AU - Fujiwara K FAU - Minami, H AU - Minami H FAU - Katakami, N AU - Katakami N FAU - Morita, S AU - Morita S FAU - Negoro, S AU - Negoro S LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20130716 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Antiemetics) RN - 0 (Morpholines) RN - 109889-09-0 (Granisetron) RN - 1NF15YR6UY (aprepitant) RN - 41575-94-4 (Carboplatin) RN - 50-02-2 (Dexamethasone) RN - 7673326042 (irinotecan) RN - 7689-03-4 (Camptothecin) SB - IM MH - Adult MH - Aged MH - Antiemetics/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Camptothecin/administration & dosage/adverse effects/analogs & derivatives MH - Carboplatin/administration & dosage/adverse effects MH - Dexamethasone/therapeutic use MH - Double-Blind Method MH - Drug Therapy, Combination MH - Endometrial Neoplasms/drug therapy MH - Female MH - Granisetron/therapeutic use MH - Humans MH - Logistic Models MH - Middle Aged MH - Morpholines/*therapeutic use MH - Neoplasms/*drug therapy MH - Ovarian Neoplasms/drug therapy MH - *Temperance MH - Treatment Outcome MH - Vomiting/chemically induced/drug therapy/*prevention & control PMC - PMC3749572 OID - NLM: PMC3749572 [Available on 08/20/14] EDAT- 2013/07/19 06:00 MHDA- 2013/11/05 06:00 CRDT- 2013/07/18 06:00 PMCR- 2014/08/20 00:00 PHST- 2013/03/05 [received] PHST- 2013/06/22 [revised] PHST- 2013/06/26 [accepted] PHST- 2013/07/16 [aheadofprint] AID - bjc2013400 [pii] AID - 10.1038/bjc.2013.400 [doi] PST - ppublish SO - Br J Cancer. 2013 Aug 20;109(4):859-65. doi: 10.1038/bjc.2013.400. Epub 2013 Jul 16. PMID- 23810467 OWN - NLM STAT- MEDLINE DA - 20130826 DCOM- 20131113 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 49 IP - 14 DP - 2013 Sep TI - A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. PG - 2972-8 LID - 10.1016/j.ejca.2013.05.020 [doi] LID - S0959-8049(13)00428-0 [pii] AB - BACKGROUND: Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648). METHODS: Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. RESULTS: 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia >/= 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) > 24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for > 24 weeks. INTERPRETATION: The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. joyce_liu@dfci.harvard.edu FAU - Liu, Joyce F AU - Liu JF FAU - Tolaney, Sara M AU - Tolaney SM FAU - Birrer, Michael AU - Birrer M FAU - Fleming, Gini F AU - Fleming GF FAU - Buss, Mary K AU - Buss MK FAU - Dahlberg, Suzanne E AU - Dahlberg SE FAU - Lee, Hang AU - Lee H FAU - Whalen, Christin AU - Whalen C FAU - Tyburski, Karin AU - Tyburski K FAU - Winer, Eric AU - Winer E FAU - Ivy, Percy AU - Ivy P FAU - Matulonis, Ursula A AU - Matulonis UA LA - eng SI - ClinicalTrials.gov/NCT01116648 GR - 3 U01 CA062490-16S2/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130627 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (AZD 2281) RN - 0 (Capsules) RN - 0 (Phthalazines) RN - 0 (Piperazines) RN - 0 (Quinazolines) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - 0 (Tablets) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.7.10.1 (Receptor, erbB-2) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - NQU9IPY4K9 (cediranib) RN - Ovarian epithelial cancer SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Capsules MH - Diarrhea/chemically induced MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Fatigue/chemically induced MH - Female MH - Humans MH - Middle Aged MH - Nausea/chemically induced MH - Neoplasm Recurrence, Local MH - Neoplasms, Glandular and Epithelial/*drug therapy/pathology MH - Ovarian Neoplasms/*drug therapy/pathology MH - Phthalazines/administration & dosage/adverse effects MH - Piperazines/administration & dosage/adverse effects MH - Poly(ADP-ribose) Polymerases/antagonists & inhibitors MH - Quinazolines/administration & dosage/adverse effects MH - Receptor, erbB-2/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors MH - Tablets MH - Treatment Outcome OTO - NOTNLM OT - Anti-angiogenic OT - Breast OT - Cediranib OT - Olaparib OT - Ovarian OT - PARP-inhibitor OT - Phase 1 EDAT- 2013/07/03 06:00 MHDA- 2013/11/14 06:00 CRDT- 2013/07/02 06:00 PHST- 2013/04/09 [received] PHST- 2013/05/13 [revised] PHST- 2013/05/16 [accepted] PHST- 2013/06/27 [aheadofprint] AID - S0959-8049(13)00428-0 [pii] AID - 10.1016/j.ejca.2013.05.020 [doi] PST - ppublish SO - Eur J Cancer. 2013 Sep;49(14):2972-8. doi: 10.1016/j.ejca.2013.05.020. Epub 2013 Jun 27. PMID- 23810466 OWN - NLM STAT- MEDLINE DA - 20130826 DCOM- 20131113 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 49 IP - 14 DP - 2013 Sep TI - A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel + 5-fluorouracil for patients with advanced gastric cancer. PG - 2995-3002 LID - 10.1016/j.ejca.2013.05.021 [doi] LID - S0959-8049(13)00429-2 [pii] AB - PURPOSE: This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR). METHODS: Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d. RESULTS: A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%. CONCLUSION: Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. AD - Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China. FAU - Huang, Dingzhi AU - Huang D FAU - Ba, Yi AU - Ba Y FAU - Xiong, Jianping AU - Xiong J FAU - Xu, Nong AU - Xu N FAU - Yan, Zhao AU - Yan Z FAU - Zhuang, Zhixiang AU - Zhuang Z FAU - Yu, Zhuang AU - Yu Z FAU - Wan, Huiping AU - Wan H FAU - Zhang, Yang AU - Zhang Y FAU - Deng, Ting AU - Deng T FAU - Zheng, Rongsheng AU - Zheng R FAU - Guo, Zengqing AU - Guo Z FAU - Hu, Chunhong AU - Hu C FAU - Wang, Meiling AU - Wang M FAU - Yu, Zhonghe AU - Yu Z FAU - Yao, Yang AU - Yao Y FAU - Meng, Jichang AU - Meng J LA - eng PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20130627 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Drug Combinations) RN - 150863-82-4 (S 1 (combination)) RN - 17902-23-7 (Tegafur) RN - 33069-62-4 (Paclitaxel) RN - 51-21-8 (Fluorouracil) RN - 58-05-9 (Leucovorin) RN - 937-13-3 (Oxonic Acid) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Aged MH - Anorexia/chemically induced MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Drug Administration Schedule MH - Drug Combinations MH - Female MH - Fluorouracil/administration & dosage/adverse effects MH - Humans MH - Infusions, Intravenous MH - Kaplan-Meier Estimate MH - Leucovorin/administration & dosage/adverse effects MH - Leukopenia/chemically induced MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Nausea/chemically induced MH - Oxonic Acid/administration & dosage/adverse effects MH - Paclitaxel/administration & dosage/adverse effects MH - Stomach Neoplasms/*drug therapy/pathology MH - Tegafur/administration & dosage/adverse effects MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Efficacy OT - Gastric cancer OT - Paclitaxel OT - S-1 OT - Safety EDAT- 2013/07/03 06:00 MHDA- 2013/11/14 06:00 CRDT- 2013/07/02 06:00 PHST- 2012/05/16 [received] PHST- 2013/03/06 [revised] PHST- 2013/05/29 [accepted] PHST- 2013/06/27 [aheadofprint] AID - S0959-8049(13)00429-2 [pii] AID - 10.1016/j.ejca.2013.05.021 [doi] PST - ppublish SO - Eur J Cancer. 2013 Sep;49(14):2995-3002. doi: 10.1016/j.ejca.2013.05.021. Epub 2013 Jun 27. PMID- 23810058 OWN - NLM STAT- MEDLINE DA - 20130708 DCOM- 20131029 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 2 DP - 2013 TI - Safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery and chemotherapy: protocol for a systematic review and network meta-analysis. PG - 46 LID - 10.1186/2046-4053-2-46 [doi] AB - BACKGROUND: Serotonin (5-HT3) receptor antagonists are a class of antiemetic medications often used to prevent nausea and vomiting among patients undergoing chemotherapy, radiotherapy or surgery. However, recent studies suggest that these agents might be associated with increased cardiac harm. To examine this further, we are proposing to conduct a systematic review and network meta-analysis on the comparative safety of 5-HT3 receptor antagonists among patients undergoing chemotherapy or surgery. METHODS/DESIGN: Studies reporting one or more safety outcomes of interest for 5-HT3 receptor antagonists compared with each other, placebo, and/or other anti-emetic agents (for example, benzamides, phenothiazines, butyrophenones, antihistamines, and anticholinergics) among children and adult patients undergoing surgery or chemotherapy will be included. Our primary outcome of interest is arrhythmia. Our secondary outcomes include cardiac death, QT prolongation, PR prolongation, all-cause mortality, nausea, and vomiting. We will include experimental studies, quasi-experimental studies (namely controlled before-after and interrupted time series), and observational studies (namely cohort studies). We will not limit inclusion by publication status, time period, duration of follow-up or language of dissemination.Electronic databases (for example, MEDLINE, EMBASE) will be searched from inception onwards. These main searches will be supplemented by searching for difficult to locate and unpublished studies, such as dissertations, and governmental reports. The eligibility criteria will be pilot-tested and subsequently used to screen the literature search results by two reviewers in duplicate. A similar process will be followed for full-text screening, data abstraction, and risk of bias/methodological quality appraisal. The Cochrane Risk of Bias tool will be used to appraise experimental and quasi-experimental studies, and cohort studies will be assessed using the Newcastle Ottawa Scale. If the data allows, random effects meta-analysis and a network (that is, mixed treatment comparisons) meta-analysis will be conducted. All analyses will be conducted separately for different study designs, patient populations (for example, children and adults), and reason for administering 5-HT3 receptor antagonists (for example, post-surgery and chemotherapy). DISCUSSION: Our results will help inform patients, clinicians, and health policy-makers about the potential safety concerns, as well as the comparative safety, of using these antiemetic agents. TRIAL REGISTRATION: PROSPERO registry number:CRD42013003564. AD - Li Ka Shing Knowledge Institute, St, Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario M5B 1T8, Canada. FAU - Tricco, Andrea C AU - Tricco AC FAU - Soobiah, Charlene AU - Soobiah C FAU - Antony, Jesmin AU - Antony J FAU - Hemmelgarn, Brenda AU - Hemmelgarn B FAU - Moher, David AU - Moher D FAU - Hutton, Brian AU - Hutton B FAU - Straus, Sharon E AU - Straus SE LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130628 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Antiemetics) RN - 0 (Serotonin 5-HT3 Receptor Antagonists) SB - IM MH - Antiemetics/*adverse effects/therapeutic use MH - Arrhythmias, Cardiac/etiology/*prevention & control MH - Humans MH - *Meta-Analysis as Topic MH - Nausea/*drug therapy/etiology/prevention & control MH - *Neoplasms/complications/therapy MH - Outcome Assessment (Health Care) MH - Research Design MH - Review Literature as Topic MH - Safety MH - Serotonin 5-HT3 Receptor Antagonists/*adverse effects/therapeutic use MH - Vomiting/*drug therapy/etiology/prevention & control PMC - PMC3702491 OID - NLM: PMC3702491 EDAT- 2013/07/03 06:00 MHDA- 2013/10/30 06:00 CRDT- 2013/07/02 06:00 PHST- 2013/02/22 [received] PHST- 2013/03/08 [accepted] PHST- 2013/06/28 [aheadofprint] AID - 2046-4053-2-46 [pii] AID - 10.1186/2046-4053-2-46 [doi] PST - epublish SO - Syst Rev. 2013 Jun 28;2:46. doi: 10.1186/2046-4053-2-46. PMID- 23809884 OWN - NLM STAT- MEDLINE DA - 20130704 DCOM- 20131029 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 2 DP - 2013 TI - Interventions to decrease the risk of adverse cardiac events for post-surgery or chemotherapy patients taking serotonin (5-HT3) receptor antagonists: protocol for a systematic review and network meta-analysis. PG - 45 LID - 10.1186/2046-4053-2-45 [doi] AB - BACKGROUND: Patients undergoing surgery or chemotherapy often experience nausea and vomiting. To increase their quality of life and treatment satisfaction, antiemetic medication, such as serotonin receptor antagonists, is often prescribed for patients experiencing these symptoms. However, early warning signs suggest that serotonin receptor antagonists can cause harm, including arrhythmia. Our objective is to identify the most effective interventions that mitigate the risk of adverse cardiac events associated with serotonin receptor antagonists in patients undergoing surgery and chemotherapy through a systematic review and network meta-analysis. METHODS/DESIGN: We will search electronic databases (for example, MEDLINE, Embase) from inception onwards, as well as dissertations and governmental reports, to identify interventions (for example, telemetry, electrocardiography, electrolyte monitoring) that decrease the cardiac risk associated with serotonin receptor antagonists among surgery and chemotherapy patients. Eligible comparators include placebo or supportive care; eligible study designs are experimental studies (randomized controlled trials (RCTs), quasi-RCTs, non-RCTs), non-experimental studies (interrupted time series, controlled before-and-after studies), and cohort studies. Outcomes of interest include arrhythmia, sudden cardiac death, QT prolongation, PR prolongation, and all-cause mortality. We will include unpublished studies and studies published in languages other than English.Draft inclusion and exclusion criteria will be established and pilot tested amongst the team. Subsequently, two team members will screen the results in duplicate and resolve conflicts through discussion. The same process will be followed to screen full-text articles, data abstraction, and appraise quality or risk of bias. To determine validity of results, experimental and quasi-experimental studies will be assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) Risk of Bias tool, while cohort studies will be appraised using the Newcastle-Ottawa Scale. We anticipate sufficient data and homogeneity to conduct random effects meta-analysis and network or mixed treatment comparisons meta-analysis, if appropriate. DISCUSSION: Our results will provide information regarding the utility of different strategies that can be used to mitigate cardiac risk amongst patients taking serotonin antagonist receptors. Such results are likely to be of use to clinicians prescribing these agents, as well as policy makers responsible for making decisions about antiemetic medications. TRIAL REGISTRATION: PROSPERO registry number: CRD42013003565. AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, ON M5B 1 T8, Canada. FAU - Tricco, Andrea C AU - Tricco AC FAU - Soobiah, Charlene AU - Soobiah C FAU - Antony, Jesmin AU - Antony J FAU - Hemmelgarn, Brenda AU - Hemmelgarn B FAU - Moher, David AU - Moher D FAU - Hutton, Brian AU - Hutton B FAU - Straus, Sharon E AU - Straus SE LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130628 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Antiemetics) RN - 0 (Serotonin 5-HT3 Receptor Antagonists) SB - IM MH - Antiemetics/*adverse effects/therapeutic use MH - Biomedical Research MH - Cardiovascular Diseases/etiology/*prevention & control MH - Humans MH - *Meta-Analysis as Topic MH - Nausea/etiology/prevention & control/*therapy MH - *Neoplasms/complications/therapy MH - Outcome Assessment (Health Care) MH - Research Design MH - Review Literature as Topic MH - Serotonin 5-HT3 Receptor Antagonists/*adverse effects/therapeutic use MH - Vomiting/etiology/prevention & control/*therapy PMC - PMC3701482 OID - NLM: PMC3701482 EDAT- 2013/07/03 06:00 MHDA- 2013/10/30 06:00 CRDT- 2013/07/02 06:00 PHST- 2013/02/22 [received] PHST- 2013/03/15 [accepted] PHST- 2013/06/28 [aheadofprint] AID - 2046-4053-2-45 [pii] AID - 10.1186/2046-4053-2-45 [doi] PST - epublish SO - Syst Rev. 2013 Jun 28;2:45. doi: 10.1186/2046-4053-2-45. PMID- 23756360 OWN - NLM STAT- MEDLINE DA - 20130826 DCOM- 20131113 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 49 IP - 14 DP - 2013 Sep TI - One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. PG - 2986-94 LID - 10.1016/j.ejca.2013.05.006 [doi] LID - S0959-8049(13)00383-3 [pii] AB - PURPOSE: We report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes. METHODS: Postmenopausal patients with breast cancer and positive nodes, deep invasion or size exceeding 5 cm were randomly assigned to 1 year of tamoxifen, or cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 intravenously on day 1 every 4 weeks for nine cycles plus tamoxifen (CMFT). Tissue microarrays were constructed retrospectively and oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and proliferation-related Ki-67 antigen (Ki67) status were assessed. RESULTS: From October 1982 through March 1990 we randomised 1445 patients and 969 (67%) were eligible for the biomarker analysis. At 10-years 936 women had suffered a disease-free survival (DFS) event (tamoxifen, 495 events in 686 patients; CMFT, 441 events in 642 patients). The addition of CMF to tamoxifen significantly improved DFS (adjusted hazard ratio 0.82; 95% confidence interval (CI) 0.71-0.93; P = 0.003) but not overall survival (adjusted hazard ratio 0.95; 95% CI 0.85-1.08; P = 0.44). DFS was superior in Luminal A tumours (ER or PgR positive, HER2 negative and Ki67