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1.
Ann Oncol ; 30(7): 1114-1120, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31020334

ABSTRACT

BACKGROUND: The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. PATIENTS AND METHODS: Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. RESULTS: CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. CONCLUSION: We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00433563.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/blood , Lung Neoplasms/therapy , Neoplastic Cells, Circulating/pathology , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Disease Progression , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Neoplastic Cells, Circulating/drug effects , Neoplastic Cells, Circulating/radiation effects , Small Cell Lung Carcinoma/pathology , Survival Rate
2.
Clin Oncol (R Coll Radiol) ; 28(12): 760-765, 2016 12.
Article in English | MEDLINE | ID: mdl-27401967

ABSTRACT

AIMS: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. MATERIALS AND METHODS: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. RESULTS: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9-73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. CONCLUSION: The data suggest that international survival statistics are achieved in UK regional cancer centres.


Subject(s)
Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Aged , Disease-Free Survival , Female , Humans , Middle Aged
3.
BMJ Open ; 6(1): e010589, 2016 Jan 27.
Article in English | MEDLINE | ID: mdl-26817643

ABSTRACT

INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results.


Subject(s)
Lung Neoplasms/prevention & control , Mesothelioma/prevention & control , Neoplasm Seeding , Pleural Neoplasms/prevention & control , Postoperative Complications/prevention & control , Adult , Aged , Ambulatory Care , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Clinical Protocols , Female , Humans , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Mesothelioma/radiotherapy , Mesothelioma/surgery , Mesothelioma, Malignant , Patient Selection , Pleural Neoplasms/radiotherapy , Pleural Neoplasms/surgery , Postoperative Care/methods , Radiotherapy, Adjuvant , Thoracic Neoplasms/prevention & control , Thoracic Neoplasms/secondary , Thoracic Wall , Treatment Outcome , Young Adult
4.
Br J Cancer ; 105(1): 22-7, 2011 Jun 28.
Article in English | MEDLINE | ID: mdl-21654687

ABSTRACT

BACKGROUND: Women at high ovarian cancer risk, especially those with mutations in BRCA1/BRCA2, are encouraged to undergo bilateral risk-reducing salpingo-oophorectomy (BRRSPO) prior to the natural menopause. The decision to use HRT to cover the period of oestrogen deprivation up to 50 years of age is difficult because of balancing the considerations of breast cancer risk, bone and cardiovascular health. METHODS: We reviewed by questionnaire 289 women after BRRSPO aged ≤48 years because of high ovarian cancer risk; 212 (73%) of women responded. RESULTS: Previous HRT users (n=67) had significantly worse endocrine symptom scores than 67 current users (P=0.006). A total of 123 (58%) of women had ≥24 months of oestrogen deprivation <50 years with 78 (37%) never taking HRT. Bone density (DXA) evaluations were available on 119 (56%) women: bone loss with a T score of ≤-1.0 was present in 5 out of 31 (16%) women with no period of oestrogen deprivation <50 years compared with 37 out of 78 (47%) of those with ≥24 months of oestrogen deprivation (P=0.03). INTERPRETATION: Women undergoing BRRSPO <50 years should be counselled concerning the risks/benefits of HRT, taking into consideration the benefits on symptoms, bone health and cardiovascular health, and that the risks of breast cancer from oestrogen-only HRT appear to be relatively small.


Subject(s)
Estrogen Replacement Therapy , Menopause , Ovarian Neoplasms/prevention & control , Ovariectomy , Salpingostomy , Adult , Aged , Aged, 80 and over , Bone and Bones , Female , Genes, BRCA1 , Genes, BRCA2 , Genetic Predisposition to Disease , Health Status , Humans , Middle Aged , Ovarian Neoplasms/genetics , Postoperative Care , Risk Assessment , Risk Factors , Treatment Outcome , Young Adult
5.
Ann Oncol ; 21(10): 2023-2028, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20332134

ABSTRACT

BACKGROUND: Some non-small-cell lung cancer (NSCLC) surgical series have indicated that the positive prognostic effect of female sex is limited to patients with adenocarcinoma. We carried out a retrospective analysis to investigate the role of sex and histology on efficacy, toxicity, and dose delivery after chemotherapy. PATIENT AND METHODS: Individual patient data were pooled from five randomized, phase III, advanced NSCLC chemotherapy trials. Primary outcomes were response rate, overall survival (OS), toxicity, and dose delivery. A secondary analysis examined survival by sex in histological subgroups. RESULTS: Of 2349 patients, 34% were women. Women had a higher response rate to chemotherapy (42% versus 40%, P = 0.01) and longer survival than men (median OS 9.6 versus 8.6 months, P = 0.002). The difference in OS remained after adjusting for age, stage, performance status, and histology (hazard ratio 0.83, 95% confidence interval 0.74-0.92, P = 0.0005). Upon further examination, longer survival in women was only seen in patients with adenocarcinoma (test for interaction P = 0.006). There were no differences in hematological toxicity or transfusions. Women experienced more grade 3-4 emesis than men (P < 0.0001) and more dose delays (P = 0.02) or dose reductions (P < 0.0001). CONCLUSION: The positive prognostic effect among women is confirmed in patients receiving platinum-based chemotherapy but appears confined to those with adenocarcinoma histology.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Quality of Life , Randomized Controlled Trials as Topic , Retrospective Studies , Sex Factors , Survival Rate , Treatment Outcome , Young Adult
6.
Ann Oncol ; 21(2): 232-237, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19675093

ABSTRACT

BACKGROUND: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC). METHODS: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates. RESULTS: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0-1/Karnofsky PS 80-100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P < 0.0001). Response rates between women and men were similar (77% versus 76%, P = 0.64). In univariate [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.006] and multivariate (HR 0.88, 95% CI 0.79-0.99, P = 0.04) analyses, female sex predicted for longer survival. Women experienced more grade 3/4 emesis (18% versus 9%, P < 0.0001) and grade 3/4 mucositis (13% versus 8%, P = 0.005) than men. There were no differences in DI, infections, transfusions or treatment-related deaths. CONCLUSION: Data from >1700 patients in randomized SCLC chemotherapy trials confirm that women survive modestly longer than men but may experience greater toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Sex Factors , Small Cell Lung Carcinoma/diagnosis , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Clinical Trials as Topic , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Small Cell Lung Carcinoma/mortality , Societies, Medical , Survival Analysis , Treatment Outcome , United Kingdom
7.
Eur J Cancer ; 42(10): 1385-90, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16750910

ABSTRACT

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.


Subject(s)
Breast Neoplasms/diagnosis , Genetic Testing/methods , Adult , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Early Diagnosis , Female , Genes, BRCA1 , Genes, BRCA2 , Heterozygote , Humans , Mammography/methods , Middle Aged , Pedigree , Survival Analysis , Treatment Outcome
8.
Ann Oncol ; 17(7): 1111-9, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16603599

ABSTRACT

BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quality of Life , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Docetaxel , Female , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Lung Neoplasms/mortality , Male , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Neoplasm Staging , Survival Analysis , Taxoids/administration & dosage , Taxoids/adverse effects , Vinblastine/administration & dosage , Vinblastine/adverse effects
9.
J Clin Oncol ; 23(10): 2136-44, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15713598

ABSTRACT

PURPOSE: This randomized phase II study compared two treatment schedules of gemcitabine in patients with non-small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity. PATIENTS AND METHODS: Patients with stage IIIb and IV NSCLC and KP

Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Karnofsky Performance Status , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/pathology , Drug Administration Schedule , Female , Humans , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , Middle Aged , Palliative Care , Quality of Life , Survival Analysis , Treatment Outcome , Gemcitabine
10.
J Clin Oncol ; 21(13): 2551-7, 2003 Jul 01.
Article in English | MEDLINE | ID: mdl-12829675

ABSTRACT

PURPOSE: Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma. PATIENTS AND METHODS: One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28. RESULTS: The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide. CONCLUSION: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dacarbazine/analogs & derivatives , Melanoma/drug therapy , Neoplasm Metastasis , Skin Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dacarbazine/administration & dosage , Disease Progression , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Injections, Subcutaneous , Interferon alpha-2 , Interferon-alpha/administration & dosage , Male , Melanoma/pathology , Middle Aged , Recombinant Proteins , Skin Neoplasms/pathology , Survival , Temozolomide , Thalidomide/administration & dosage
11.
Br J Cancer ; 87(5): 562-6, 2002 Aug 27.
Article in English | MEDLINE | ID: mdl-12189557

ABSTRACT

Patients who are treated within clinical trials may have a survival benefit dependent on being a trial participant. A number of factors may produce such beneficial outcome including more rigorous adherence to a peer reviewed trial protocol, management by an experienced treatment team, being treated in a specialist centre etc. The current investigation compared patients treated on and off trial with the same standard arm treatment regimen. The results could then be interpreted without the confounding factors of differing treatment regimens, treatment teams or treatment hospitals. The results demonstrated given these circumstances that survival was no different for patients participating in a randomised trial compared with a group of patients similarly treated who were not eligible for trial entry or who declined randomisation. These results were obtained by the rigorous adherence to a defined protocol with the invaluable assistance of designated lung cancer staff.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Clinical Trials as Topic , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Small Cell/mortality , Clinical Trials, Phase III as Topic , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Life Tables , Lung Neoplasms/mortality , Male , Middle Aged , Patient Acceptance of Health Care , Patient Selection , Prognosis , Randomized Controlled Trials as Topic , Remission Induction , Retrospective Studies , Survival Analysis , Treatment Refusal
12.
Ann Oncol ; 11(2): 201-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10761756

ABSTRACT

BACKGROUND: A randomised phase II study was performed to compare standard combination chemotherapy containing cisplatin and etoposide with infusional carboplatin. PATIENTS AND METHODS: One hundred twenty patients with locally advanced/metastatic non-small-cell lung cancer or mesothelioma were enrolled. All were chemotherapy-naïve and had a Karnofsky performance status of > or = 50. Patients were randomised to either four cycles of bolus therapy of cisplatin 80 mg/m2 day 1, etoposide 120 mg/m2 day 1-3, or continuous infusion of carboplatin 100/mg/m2/week for six weeks. RESULTS: No patients on infusional therapy incurred grade 3-4 toxicity while in the bolus arm, grade 3 and grade 4 leucopenia occurred in 17% and 35% of patients, respectively. Grade 4 thrombocytopenia occurred in 8% of patients and there were two instances of grade 3 renal toxicity. No responses occurred in the pump arm. Eight of forty-six patients with non-small-cell lung cancer responded to treatment (response rate 17.3%) with two complete responses and six partial responses. Only one patient with mesothelioma responded to bolus therapy. There was no difference in survival for the subset of NSCLC patients. Survival for mesothelioma patients in the pump arm was superior but this was likely to be a result of early deaths in the bolus arm. CONCLUSIONS: The pump arm was well-tolerated but not active, whilst combination platinum-based therapy demonstrated activity but significantly more toxicity than the pump arm. Further studies of infusional carboplatin with this schedule are not warranted.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Adult , Aged , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Confidence Intervals , Disease-Free Survival , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Male , Mesothelioma/diagnosis , Mesothelioma/mortality , Middle Aged , Neoplasm Staging , Survival Rate , Treatment Outcome
13.
Br J Cancer ; 82(6): 1158-62, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10735499

ABSTRACT

The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. The trial was designed to detect a 25% absolute difference in response rate or in 1-year survival with 80% power. There was no significant difference in response rate: this was 17.3% with DTIC/IFN and 26.4% with DBCT. Median overall survival was similar at 199 and 202 days respectively. One-year survival rate favoured standard treatment (30.6 vs 22.6%), but did not differ significantly between arms. DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Interferon-alpha/administration & dosage , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Carmustine/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Dacarbazine/administration & dosage , Disease Progression , Female , Humans , Interferon-alpha/pharmacology , Male , Melanoma/pathology , Middle Aged , Skin Neoplasms/pathology , Survival Analysis , Tamoxifen/administration & dosage , Treatment Outcome
14.
Br J Cancer ; 78(3): 366-9, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9703284

ABSTRACT

A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Interferon-alpha/administration & dosage , Interleukin-2/therapeutic use , Kidney Neoplasms/drug therapy , Adult , Aged , Fatigue/chemically induced , Female , Humans , Interferon-alpha/adverse effects , Interleukin-2/administration & dosage , Interleukin-2/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Vomiting/chemically induced
15.
Br J Cancer ; 67(6): 1385-90, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8390287

ABSTRACT

One hundred and fifty-nine previously untreated patients with small cell lung cancer (SCLC), who were not eligible for intensive chemotherapy, were entered into a randomised study of intravenous (i.v.) doxorubicin and ifosfamide (with mesna) and oral etoposide. The i.v. drugs were given either by bolus therapy or by a continuous infusion (CI) pump over 7 days via a central venous line. Therapy was given for 6 weeks only. On weeks 1, 3 and 5 IV doxorubicin 35 mg m-2 was given with 5 days of oral etoposide 100 mg m-2 daily. On weeks 2, 4 and 6 IV ifosfamide 5 g m-2 was given with equidose mesna. The overall median survival was 25 weeks for patients in the bolus arm and 30 weeks for the CI therapy (P = 0.45). The overall response rate was 64% (18% complete response-CR) and 69% (30% CR) respectively (P = 0.13). The median WHO score for haematological toxicity was 4 for bolus therapy and 3 for CI therapy (P = 0.0007). Despite a trend for less supportive care for patients on CI therapy there were no significant differences in the use of i.v. antibodies and blood or platelet transfusions. There were fewer treatment delays due to myelotoxicity in the CI arm (P = 0.04). The median WHO score for non-haematological toxicity was 2 in both treatment groups. There was significantly less nausea (P = 0.037) but more mucositis (P = 0.01) in the CI arm. Weekly chemotherapy using CI treatment was as effective as bolus therapy. It was well accepted by patients. The assessment of quality of life in a subgroup of patients showed a statistically significant reduction in anxiety and depression for both groups of patients during therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Small Cell/drug therapy , Infusion Pumps , Lung Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Small Cell/psychology , Doxorubicin/administration & dosage , Drug Administration Schedule , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Infusions, Intravenous , Lung Neoplasms/psychology , Male , Middle Aged , Quality of Life
16.
Cancer Chemother Pharmacol ; 28(2): 142-4, 1991.
Article in English | MEDLINE | ID: mdl-1647893

ABSTRACT

A total of 45 patients with advanced non-small-cell lung cancer were treated with a combination of 1.5 g/m2 ifosfamide given on days 1-5 every 3 weeks for four courses with 3 million IU a2b-interferon (Intron A) given s.c. three times a week for 12 weeks. Nine objective responses were seen, including two complete responses (CRs) and seven partial responses (PRs). Haematological and non-haematological toxicities were generally mild and did not necessitate discontinuation of therapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Ifosfamide/therapeutic use , Interferon-alpha/therapeutic use , Lung Neoplasms/drug therapy , Adult , Aged , Drug Evaluation , Female , Humans , Ifosfamide/adverse effects , Interferon alpha-2 , Male , Middle Aged , Recombinant Proteins
17.
Drug Alcohol Depend ; 17(4): 331-8, 1986 Jul.
Article in English | MEDLINE | ID: mdl-3757769

ABSTRACT

Alterations in central dopamine function have been identified in depression and in alcohol withdrawal. Attempts to determine the magnitude and direction of the central dopamine alteration in alcohol withdrawal have produced conflicting results. In this study serum prolactin (PRL) was used as an indicator of central dopamine activity since dopamine is the most important factor in the control of prolactin secretion from the pituitary. Increased serum PRL levels were found during alcohol withdrawal and they correlated significantly with high scores on the Hamilton Depression Rating Scale (HDRS). No significant correlations were identified with The Brief Psychiatric Rating Scale (BPRS), the 'Mini-Mental State' of Folstein (MMS), The Beck Depression Inventory (BDI) or The Modified Gross Alcohol Withdrawal Selective Severity Assessment Scale (GAWSSA). The authors concluded that the transient depressive symptomatology typically found in detoxifying alcoholic patients may be, in part, the result of a central hypodopaminergic state.


Subject(s)
Alcoholism/blood , Depression/blood , Prolactin/blood , Substance Withdrawal Syndrome/blood , Adult , Alcoholism/complications , Depression/chemically induced , Dopamine/metabolism , Humans , Male , Middle Aged , Psychiatric Status Rating Scales
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