Abstract：
BACKGROUND:This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients. METHODS:Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age. RESULTS:One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3-5 toxicities (22.8% vs 24.8% (P=0.52)), trial discontinuation (6% vs 4%; P=0.33), and dose interruptions (8.0% vs 8.0% (P=0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome. CONCLUSIONS:Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Khan KH,Yap TA,Ring A,Molife LR,Bodla S,Thomas K,Zivi A,Smith A,Judson I,Banerji U,de Bono JS,Kaye SBdoi
10.1038/bjc.2015.477subject
Has Abstractpub_date
2016-02-02 00:00:00pages
262-8issue
3eissn
0007-0920issn
1532-1827pii
bjc2015477journal_volume
114pub_type
杂志文章abstract：:Cancer incidence in the Falkland Islands, 1989-2000, was compared with rates in England and Wales, from which most Islanders originate. Colon and rectum cancer incidence was significantly raised 1989-93 but greatly reduced after 1994, when colonoscopic screening in high-risk families and sigmoidoscopic screening in th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2099
更新日期：2001-11-02 00:00:00
abstract：BACKGROUND:Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated. METHODS:We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.339
更新日期：2013-07-23 00:00:00
abstract：:The National Registry of Childhood Tumours contains over 51000 records of children born in Great Britain who developed cancer under the age of 15 years. Patterns of childhood cancer among families containing more than one child with cancer have been studied. A total of 225 "sib pair' families have been ascertained fro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.331
更新日期：1996-07-01 00:00:00
abstract：:Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.451
更新日期：1998-07-01 00:00:00
abstract：:A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non-...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1995.255
更新日期：1995-06-01 00:00:00
abstract：:Studies in animal models of mouse mammary carcinoma have shown that ovine submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective in stimulating an immune response and inhibiting tumour growth. In similar studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide has bee...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1996.532
更新日期：1996-10-01 00:00:00
abstract：BACKGROUND:CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation. METHODS:We evaluated the expression of CD70 in biopsies and melano...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.412
更新日期：2016-01-12 00:00:00
abstract：:The large numbers of papillary thyroid carcinomas that have occurred in those exposed to high levels of short-lived isotopes in fallout after Chernobyl provide a unique opportunity to correlate latency and tumour biology. We show that short latency is associated with tumours with a phenotype that is significantly less...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601860
更新日期：2004-06-01 00:00:00
abstract：:We have evaluated the relation between cancer of the lower urinary tract ("bladder cancer") and the use of artificial sweeteners, by means of case-control studies in Manchester, U.K., and Nagoya, Japan, areas where extensive use occurred 30-40 years ago. In each area, a broadly based series of cases (555 in Manchester...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.59
更新日期：1982-03-01 00:00:00
abstract：:In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600144
更新日期：2002-03-04 00:00:00
abstract：:Somatostatin analogues may be useful novel agents in the systemic treatment of advanced colorectal cancer, as somatostatin inhibits proliferation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor subty...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.59
更新日期：1997-01-01 00:00:00
abstract：:Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, mor...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-019-0509-3
更新日期：2019-08-01 00:00:00
abstract：BACKGROUND:On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs. METHO...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.23
更新日期：2011-03-01 00:00:00
abstract：:A long term follow-up study has been undertaken in 33 patients with acute non-lymphoblastic leukaemia (ANLL) in order to establish whether a correlation exists between the clinical course and the immunologic pattern of lymphoid subpopulations. Peripheral blood lymphoid cells have been investigated longitudinally (each...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.221
更新日期：1988-09-01 00:00:00
abstract：:Fifty patients affected by histologically confirmed gastrointestinal tract cancer (GTC) were treated with oral tegafur (TG) 1,000 mg m-2 p.o. on days 1-14 repeated after a 14 day interval. Out of 42 evaluable patients seven patients had a partial response (PR. 17%) with a median duration of 20.5 weeks, three had a min...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.105
更新日期：1990-03-01 00:00:00
abstract：BACKGROUND:Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. T...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.236
更新日期：2012-07-10 00:00:00
abstract：:To estimate the prevalence of TP53 mutations in familial breast cancer, constant denaturant gel electrophoresis (CDGE) was used to screen exons 5-8 of the TP53 gene for germline mutations. Genomic DNA from 128 breast cancer patients belonging to 109 families with familial cancer were screened. No germline mutations we...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.205
更新日期：1997-01-01 00:00:00
abstract：:A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.421
更新日期：1990-12-01 00:00:00
abstract：:The efficacy of photodynamic therapy (PDT) using delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.584
更新日期：1996-11-01 00:00:00
abstract：:In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same se...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/sj.bjc.6604136
更新日期：2008-01-15 00:00:00
abstract：:Foetal acinar components associated with the development of the hamster pancreas have been previously defined with the aid of an antifoetal pancreas serum. In immunohistology this antiserum also stained malignant ductal cells in N-nitrobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma. It did not stain a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.28
更新日期：1985-02-01 00:00:00
abstract：BACKGROUND:Patients with borderline resectable pancreatic cancer (BRPC) have poor prognosis with upfront surgery. METHODS:This was a single-arm Phase 2 trial for clinical and biomarker analysis. The primary endpoint is 1-year progression-free survival (PFS) rate. Patients received 8 cycles of neoadjuvant modified (m) ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0867-x
更新日期：2020-08-01 00:00:00
abstract：BACKGROUND:MicroRNA (miRNA)-126 (miR-126) is an endothelial-specific miRNA located within intron 7 of epidermal growth factor-like domain 7 (EGFL7). However, the role of miR-126 in cancer is controversial. METHODS:We examined the function of miR-126 in oral squamous cell carcinoma (OSCC) cells. Furthermore, a series o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.330
更新日期：2012-08-07 00:00:00
abstract：:An antigen common to human sarcomas, S3, has been further characterized. It is antigenically distinct from human blood-group substances A and B and from heterophile antigens such as Forssman, infectious mononucleosis and serum sickness antigens. Whilst S3 antigen preparations may contain small amounts of CEA and AFP t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.43
更新日期：1981-03-01 00:00:00
abstract：:A total of 165 adult patients with Hodgkin's disease (HD) were questioned following treatment to examine their perceptions of actual and desired involvement and provision of information in the treatment decision-making process. Irrespective of the degree to which patients felt they had been involved in the decision-ma...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.39
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND:Epidemiological studies evaluating the association of vitamin B6, vitamin B12 and methionine with breast cancer risk have produced inconsistent results. METHODS:Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose-response relationship was assessed...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/bjc.2013.438
更新日期：2013-10-01 00:00:00
abstract：:P450 reductase (NADPH:cytochrome P450 reductase, EC 1.6.2.4) is known to be important in the reductive activation of the benzotriazene-di-N-oxide tirapazamine (SR 4233). Using a panel of six human breast adenocarcinoma cell lines we have examined the relationship between P450 reductase activity and sensitivity to tira...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.478
更新日期：1995-11-01 00:00:00
abstract：:The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attend...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.387
更新日期：1996-08-01 00:00:00
abstract：:The efficacy of cisplatin [cis-diamminedichloroplatinum (II); DDP] is hampered by acquired or de novo resistance of malignant cells to its cytotoxic effects. We have previously reported that cisplatin resistance parallels glutathione S-transferase (GST) activity in several human small-cell lung cancer cell lines. In t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.278
更新日期：1994-08-01 00:00:00
abstract：:Van Trommel et al have previously shown that serum human chorionic gonadotropin (hCG) cutoff levels can provide early prediction of resistance to first-line methotrexate (MTX) in patients with persistent trophoblastic disease (PTD). In this study, we validate this approach of prediction of resistance to single-agent c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604849
更新日期：2009-03-24 00:00:00
