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Port Glasgow, United Kingdom

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.


Denschlag D.,ESGO Task Force for Fertility Preservation | Reed N.S.,Beatson Oncology Center | Rodolakis A.,ESGO Task Force for Fertility Preservation
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.


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.


Reed N.,Beatson Oncology Center
Current Oncology Reports | Year: 2013

Uterine leiomyosarcomas are rare but challenging tumours. They occur most commonly around or shortly after the menopause. Their clinical behaviour is very variable, from highly aggressive to very indolent. Most are diagnosed unexpectedly and thus initially operated on by general gynaecologists. This article discusses the important surgical issues and the role of adjuvant treatments such as radiotherapy and chemotherapy. Important new international trials are opening to address these issues. Relapsed disease is usually incurable, but a subgroup of patients may benefit from repeated surgical procedures, hormones and ablative therapies. The choice of drugs for chemotherapy is discussed. New approaches with targeted agents have yet to establish themselves in treatment of leiomyosarcomas. © 2013 Springer Science+Business Media New York.


Verheijen R.H.M.,University Utrecht | Cibula D.,Charles University | Zola P.,Ospedale Mauriziano Umberto I | Reed N.,Beatson Oncology Center
International Journal of Gynecological Cancer | Year: 2012

A recent study on the use of cancer antigen 125 (CA-125) in follow-up of patients with epithelial ovarian cancer after complete response on primary treatment is critically reviewed. As it has been suggested to refrain from CA-125 altogether, this European Society of Gynaecologic Oncology report has also reviewed possible disadvantages, even possible harm, and potentially missed opportunities when such policy would be implemented. It is concluded that indeed routine use of CA-125 does not provide patient benefit in survival or quality of life. However, there may be other reasons for monitoring CA-125, which are discussed in this review. It is noted that the lack of benefit of CA-125 monitoring has only been proven for a specific subset of ovarian cancer patients with serous histology and frequent follow-up visits including imaging and in a clinical environment where, particularly, surgery for recurrent disease and clinical studies on new second-line agents will not be considered. A special warning is issued not to stop tumor marker follow-up in other than epithelial ovarian cancers and in follow-up of patients who not have been treated with chemotherapy. Copyright © 2012 by IGCS and ESGO.

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