Abstract:
:A multicentric, prospective phase III study was carried out with the aim of testing the so-called 'worst drug rule' hypothesis, which suggests the use of an effective but 'less active' regimen that first eradicates tumoral cells resistant to a second effective and 'more active' regimen. With respect to this hypothesis, we considered the cisplatin plus vinorelbine regimen (CCDP/VNR) as the more active regimen compared with the non-cisplatin-containing regimen of ifosfamide plus high-dose epirubicin (IFO/EPI). Thus, a randomized study was carried out to compare the sequencial strategy of three cycles of CDDP/VNR followed by three cycles of IFO/EPI with the opposite sequence in advanced non-small-cell lung cancer. A total of 100 consecutive previously untreated patients with stage III-IV non-small-cell lung cancer were centrally randomized in two arms according to stage of disease and the performance status. Patients allocated to arm A received CDDP (100 mg m-2 on day 1) plus VNR (25 mg m-2 i.v. on days 1 and 8) every 21 days for three cycles (step 1) followed, after restaging, by three cycles of IFO (2.5 g m-2 with mesna on day 1) plus high-dose EPI (100 mg m-2 on day 1) every 21 days (step 2). Patients in arm B received the opposite sequence. Type and rates of objective response were evaluated after step 1 and step 2 in agreement with WHO criteria and an intent-to-treat analysis. Patients were also analysed for toxicity patterns, time to progression and survival. After the first three cycles (step 1), overall response rate (ORR), calculated according to an intent-to-treat analysis, was 47% and 21% for arm A and arm B respectively (P = 0.0112). ORR for stage III patients was 55% and 14% for arm A and B respectively (P = 0.0097). In stage IV patients ORR was higher in arm A than in arm B (42% vs 28%) but not statistically significant (P = 0.4). Clinical responses to the shift of chemotherapy (step 2) showed that no patient pretreated with CDDP/VNR and subsequently treated with IFO/EPI showed further response, whereas in the inverse sequence arm CDDP/VNR was able to induce 26% partial response (PR) rate in patients pretreated with IFO/EPI. This difference was statistically significant (P = 0.037). The overall median time to progression (TTP) of arm A and arm B did not significantly differ (6 vs 4 months; P = 0.665). However, median TTP of stage III patients was, respectively, 7 months for arm A and only 3 months for arm B. This difference was statistically significant (P = 0.049). Median overall survival (OS) was 9 and 7 months respectively for arm A and arm B. Despite this trend the difference was not significant (P = 0.328). Median OS of stage III patients showed a statistically significant advantage for arm A over arm B (13 vs 7 months, P = 0.03). In addition, no statistically significant difference in OS was recorded for stage IV patients (both arms 7 months, P = 0.526). Our data do not confirm Day's 'worst drug rule' hypothesis, at least in patients with advanced non-small-cell lung cancer treated with the above-mentioned regimens. The combination of CDDP and VNR seems more active, at least in terms of response rate, than the IFO/EPI, which performed poorly.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Colucci G,Gebbia V,Galetta D,Riccardi F,Cariello S,Gebbia Ndoi
10.1038/bjc.1997.586subject
Has Abstractpub_date
1997-01-01 00:00:00pages
1509-17issue
11eissn
0007-0920issn
1532-1827journal_volume
76pub_type
临床试验,杂志文章,多中心研究,随机对照试验abstract::Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.302
更新日期:1988-12-01 00:00:00
abstract::An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602040
更新日期:2004-08-31 00:00:00
abstract:BACKGROUND:There are currently two million cancer survivors in the United Kingdom, and in recent years this number has grown by 3% per annum. The aim of this paper is to provide long-term projections of cancer prevalence in the United Kingdom. METHODS:National cancer registry data for England were used to estimate can...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.366
更新日期:2012-09-25 00:00:00
abstract::Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n = 7) intracellular pH (pHi) of the brain was 7.03 +/- 0.02 (mean +/- s.e.m.). The pHi did not vary between superficial (2 cm, m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.300
更新日期:1989-09-01 00:00:00
abstract:BACKGROUND:Increased survival after cancer in young age has made long-term follow-up studies of high external validity important. In this national cohort study, we explored the impact of cancer in young age on reproduction and marital status in male survivors. METHODS:Hazard ratios (HRs) and relative risks (RRs) of re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.455
更新日期:2016-02-02 00:00:00
abstract::The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605821
更新日期:2010-08-10 00:00:00
abstract::Peripheral blood mononuclear cells (PBMCs) were obtained from patients receiving radioactive murine monoclonal antibody (MAb) therapy for malignant epithelial tumours, as well as normal controls, and were tested for the ability of T cells to proliferate in vitro in the presence of the MAb administered for therapy (HMF...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.337
更新日期:1991-09-01 00:00:00
abstract::In oncology, prognostic markers are clinical measures used to help elicit an individual patient's risk of a future outcome, such as recurrence of disease after primary treatment. They thus facilitate individual treatment choice and aid in patient counselling. Evidence-based results regarding prognostic markers are the...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6604999
更新日期:2009-04-21 00:00:00
abstract:BACKGROUND:The percentage of tumour stroma (TSP) has recently been reported to be a novel independent predictor of outcome in patients with a variety of common solid organ tumours. The aim of this study was to examine the relationship between TSP, clinicopathological characteristics and outcome in patients with invasiv...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.279
更新日期:2014-07-08 00:00:00
abstract::The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.bjc.6602799
更新日期:2005-10-17 00:00:00
abstract::Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600598
更新日期:2002-11-04 00:00:00
abstract::Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered th...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602752
更新日期:2005-09-19 00:00:00
abstract::Electron spin resonance (ESR) spectroscopy was used to examine changes in the concentration of paramagnetic metal ions in Yoshida tumours carried by female Wistar rats. Blood, spleen and lymph nodes from these animals were also examined by ESR. A decrease in the concentration of a paramagnetic species associated with ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.211
更新日期:1976-11-01 00:00:00
abstract:BACKGROUND:Selecting patients with 'sufficient life expectancy' for Phase I oncology trials remains challenging. The Royal Marsden Hospital Score (RMS) previously identified high-risk patients as those with ≥ 2 of the following: albumin <35 g l(-1); LDH > upper limit of normal; >2 metastatic sites. This study developed...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.371
更新日期:2012-09-25 00:00:00
abstract:BACKGROUND:Limited literature on the role of intraarterial chemotherapy as first-line therapy for penile squamous cell carcinoma is available. METHODS:From 2005 to 2013, a total of 12 patients with various stages of penile squamous cell carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used we...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.394
更新日期:2014-09-09 00:00:00
abstract::This paper investigates the potential for long-term survivorship for young patients diagnosed with Ewing's sarcoma. Data are examined from two successive UKCCSG Ewing's Tumour studies (ET-1 and ET-2). Patients have been followed for up to 20 years. These studies had suggested that better 5-year survival with ET-2 over...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601955
更新日期:2004-07-19 00:00:00
abstract::To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603171
更新日期:2006-06-05 00:00:00
abstract::Forty-two patients with small cell lung cancer were treated with a combination of carboplatin, ifosfamide and etoposide. Vincristine was given on day 14 of each course, the courses being repeated every 28 days for a maximum of six. Thoracic radiotherapy was given 4 weeks after the last course of chemotherapy but no pr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.228
更新日期:1989-07-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most malignant human tumours because of its high incidence of metastasis. The mechanisms underlying the metastasis of HCC, however, remain poorly understood. In this study, we performed cDNA microarray analysis to profile gene expression patterns in two subtypes of HCC, sol...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601749
更新日期:2004-06-14 00:00:00
abstract::Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604431
更新日期:2008-07-08 00:00:00
abstract:BACKGROUND:The role of processed meat in the aetiology of several cancers was explored in detail. METHODS:In the time period 1996-2004, a multisite case-control study was conducted in Montevideo, Uruguay. The study included 6 060 participants (3 528 cases and 2 532 controls) corresponding to cancers of the oral cavity...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2012.433
更新日期:2012-10-23 00:00:00
abstract::The present study investigates the role of nitric oxide and the involvement of nitric oxide synthase II isoform on the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29. HRT-18 cells, which constitutively express nitric oxide synthase II mRNA were three-fold more invasive in a Matrigel invasion a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600224
更新日期:2002-04-22 00:00:00
abstract::The tissue-specific translation elongation factor eEF1A2 is a potential oncogene that is overexpressed in human ovarian cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making analysis with commercial antibodies difficult. We wanted to establish the express...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603748
更新日期:2007-05-21 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:BACKGROUND:Heat shock protein 90 (HSP90) has a key role in the maintenance of the cellular proteostasis. However, HSP90 is also involved in stabilisation of oncogenic client proteins and facilitates oncogene addiction and cancer cell survival. The development of HSP90 inhibitors for cancer treatment is an area of growi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.710
更新日期:2014-01-07 00:00:00
abstract::Serum laminin P1 was studied in patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), respiratory infections, pulmonary fibrosis, and in normal subjects. The level of serum laminin P1 was elevated (greater than 1.27 U ml-1) in 58.9% of SCLC and in 11.5% of NSCLC patients. Median value in SCL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.123
更新日期:1992-04-01 00:00:00
abstract::The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600931
更新日期:2003-05-19 00:00:00
abstract:BACKGROUND:Determining the rate of breast cancer (BC) growth in vivo, which can predict prognosis, has remained elusive despite its relevance for treatment, screening recommendations and medicolegal practice. We developed a model that predicts the rate of in vivo tumour growth using a unique study cohort of BC patients...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/s41416-019-0539-x
更新日期:2019-09-01 00:00:00
abstract::Associations between work in the electrical and electronic industry and cancer incidence were assessed using data for 371 890 cancers registered in England between 1981 and 1987, of which 7981 were in electrical workers. Proportional registration ratios (PRRs) were calculated, both with and without the commonest cance...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.167
更新日期:1996-04-01 00:00:00
abstract::Cytotoxic antibodies to antigens specific for leukaemic myeloblasts have been sought in the serum of patients with acute myeloblastic leukaemia treated by immunotherapy with irradiated allogeneic myeloblasts and BCG. Assays of complement- and K-cell-mediated activity were used. Cytotoxicity to allogeneic myeloblasts w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.40
更新日期:1977-03-01 00:00:00