Coleman R.E.,Park University |
Winter M.C.,Park University |
Cameron D.,University of Leeds |
Bell R.,Andrew Love Cancer Center |
And 9 more authors.
British Journal of Cancer | Year: 2010
Background:Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups.Methods:In total, 205 patients received neoadjuvant CTZOL (CTZOL, n102; CT, n103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n195), outcome differences between groups were assessed adjusting for potential response modifiers.Results:Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CTZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5-20.4 mm; P0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CTZOL group (P0.146). There was no difference in axillary nodal involvement (P0.6315).Conclusion:These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies. © 2010 Cancer Research UK All rights reserved.
Denschlag D.,ESGO Task Force for Fertility Preservation |
Reed N.S.,Beatson Oncology Center
Current Oncology Reports | Year: 2012
Preservation of fertility has become a very important issue in gynecologic oncology of the young. Owing to the clinical importance of appropriate management of young patients with gynecologic cancer, the European Society of Gynecological Oncology (ESGO) decided in 2007 to launch the Task Force for Fertility Preservation in Gynecologic Cancer. This task force is supposed to promote knowledge of infertility induced by treatment of gynecologic cancers among health care workers and the public through national and international collaboration among oncologists, reproductive specialists, and allied health workers to promote research and education and to develop new strategies for fertility preservation. This article summarizes all the past and current activities of this task force. © Springer Science+Business Media, LLC 2012.
James R.D.,Kent Cancer Center |
Glynne-Jones R.,Mount Vernon Hospital |
Meadows H.M.,University College London |
Cunningham D.,Royal Marsden Hospital |
And 13 more authors.
The Lancet Oncology | Year: 2013
Background: Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival. Methods: In this 2×2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m2 on day 1) or cisplatin (60 mg/m2 on days 1 and 29), with fluorouracil (1000 mg/m2 per day on days 1-4 and 29-32) and radiotherapy (50·4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com, number 26715889. Findings: We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5·1 years (IQR 3·9-6·9). 391 of 432 (90·5%) patients in the mitomycin group versus 386 of 431 (89·6%) in the cisplatin group had a complete response at 26 weeks (difference -0·9%, 95% CI -4·9 to 3·1; p=0·64). Overall, toxic effects were similar in each group (334/472 [71%] for mitomycin vs 337/468 [72%] for cisplatin). The most common grade 3-4 toxic effects were skin (228/472 [48%] vs 222/468 [47%]), pain (122/472 [26%] vs 135/468 [29%]), haematological (124/472 [26%] vs 73/468 [16%]), and gastrointestinal (75/472 [16%] vs 85/468 [18%]). 3-year progression-free survival was 74% (95% CI 69-77; maintenance) versus 73% (95% CI 68-77; no maintenance; hazard ratio 0·95, 95% CI 0·75-1·21; p=0·70). Interpretation: The results of our trial-the largest in anal cancer to date-show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK. Funding: Cancer Research UK. © 2013 Elsevier Ltd.
Viswanathan A.N.,Harvard University |
Creutzberg C.L.,Leiden University |
Craighead P.,Tom Baker Cancer Center |
McCormack M.,University College London |
And 10 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). Methods and Materials: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. Results: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). Conclusion: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.
Park S.B.,University College London |
Park S.B.,University of New South Wales |
Goldstein D.,University of New South Wales |
Krishnan A.V.,University of New South Wales |
And 5 more authors.
CA Cancer Journal for Clinicians | Year: 2013
With a 3-fold increase in the number of cancer survivors noted since the 1970s, there are now over 28 million cancer survivors worldwide. Accordingly, there is a heightened awareness of long-term toxicities and the impact on quality of life following treatment in cancer survivors. This review will address the increasing importance and challenge of chemotherapy-induced neurotoxicity, with a focus on neuropathy associated with the treatment of breast cancer, colorectal cancer, testicular cancer, and hematological cancers. An overview of the diagnosis, symptomatology, and pathophysiology of chemotherapy-induced peripheral neuropathy will be provided, with a critical analysis of assessment strategies, neuroprotective approaches, and potential treatments. The review will concentrate on neuropathy associated with taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib, providing clinical information specific to these chemotherapies. CA Cancer J Clin 2013;63:419-437. © 2013 American Cancer Society, Inc.
Boland J.W.,University of Hull |
McWilliams K.,Beatson Oncology Center |
Ahmedzai S.H.,University of Sheffield |
Pockley A.G.,Nottingham Trent University
British Journal of Cancer | Year: 2014
Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group. © 2014 Cancer Research UK.
Sadozye A.H.,Beatson Oncology Center |
Reed N.,Beatson Oncology Center
Current Oncology Reports | Year: 2012
Brachytherapy is an essential part of radiotherapy treatment for cervical cancer. Over the decades, it has evolved from manual loading of radium and caesium to remote afterloaders and from low-dose and medium-dose rates to highdose rates. Over the past 10 years, 3D image-based Brachytherapy has evolved and established itself as the gold standard, improving local control and overall survival, and significantly reducing toxicity. In this article, we review some of the available literature on gynaecologic brachytherapy, more specifically on topics such as dose rates, high-dose-rate/pulsed-doserate (HDR/PDR) brachytherapy and image-based brachytherapy (IBBT), and present some of the evidence that establishes IBBT. © Springer Science+Business Media, LLC 2012.
Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial
Gore M.E.,Royal Marsden Hospital NHS Trust |
Griffin C.L.,Medical Research Council Clinical Trials Unit |
Hancock B.,Weston Park Hospital |
Patel P.M.,University of Nottingham |
And 10 more authors.
The Lancet | Year: 2010
Background: In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods: RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings: 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8-52·3). Median overall survival was 18·8 months (17·0-23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5-20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90-1·21], p=0·55; absolute difference 0·3% (-5·1 to 5·6) at 1 year and 2·7% (-8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation: Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. Funding: UK Medical Research Council. © 2010 Elsevier Ltd. All rights reserved.
Lolkema M.P.,Phase I Unit |
Lolkema M.P.,University Utrecht |
Arkenau H.-T.,Phase I Unit |
Harrington K.,Cancer Research UK Research Institute |
And 9 more authors.
Clinical Cancer Research | Year: 2011
Purpose: This study combined systemic administration of the oncolytic reovirus type 3 Dearing (reovirus) with chemotherapy in human subjects. We aimed to determine the safety and feasibility of combining reovirus administration with gemcitabine and to describe the effects of gemcitabine on the antireoviral immune response. Experimental Design: Patients received reovirus in various doses, initially we dosed for five consecutive days but this was poorly tolerated. We amended the protocol to administer a single dose and administered up to 3 × 1010 TCID50. Toxicity was assessed by monitoring of clinical and laboratory measurements. We assessed antibody response by cytotoxicity neutralization assay. Results: Sixteen patients received 47 cycles of reovirus. The two initial patients and one patient in the final cohort experienced dose limiting toxicity (DLT). The DLTs consisted of two asymptomatic grade 3 liver enzyme rises and one asymptomatic grade 3 troponin I rise. Common toxicities consisted of known reovirus and gemcitabine associated side effects. Further analysis showed a potential interaction between reovirus and gemcitabine in causing liver enzyme rises. Grade 3 rises in liver enzymes were associated with concomitant aminocetophen use. Importantly, the duration of the liver enzyme rise was short and reversible. Neutralizing antibody responses to reovirus were attenuated both in time-to-occurrence and peak height of the response. Conclusions: Reovirus at the dose of 1×1010 TCID 50 can be safely combined with full dose gemcitabine. Combination of reovirus with gemcitabine affects the neutralizing antibody response and this could impact both safety and efficacy of this treatment schedule. ©2010 AACR.
Zweifel M.,Mount Vernon Cancer Center |
Jayson G.C.,University of Manchester |
Reed N.S.,Beatson Oncology Center |
Osborne R.,Poole Hospital NHS Foundation Trust |
And 8 more authors.
Annals of Oncology | Year: 2011
Background: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. Patients and methods: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m 2 minimum 18 h before paclitaxel 175 mg/m 2 and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. Results: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.