- Email: [email protected]
Toxicity of Hypofractionated Accelerated Radiotherapy Concurrent with Chemotherapy for Non-small Cell Carcinoma of the Lung
Letters / Clinical Oncology 23 (2011) 558e563
should be informed, including the potential inability to drive. These precautions should also be taken with other drugs such as paclitaxel and etoposide. It might be worth undertaking a study measuring blood alcohol levels after infusion of these agents to determine if the legal limit of blood alcohol concentration for driving is frequently exceeded. Finally, the drug company should consider continuing the manufacture of docetaxel in its older formulation for the benefit of patients who cannot tolerate the high alcohol content. A. Mirza, N. Mithal Maidstone Hospital, Maidstone, UK
561
References [1] European Medicines Agency. Evaluation of medicines for human use, EMA/774985/2009. London: European Medicines Agency; 2009. [2] http://www.medicines.org.uk/EMC/pdfviewer.aspx?isAttachment¼ true&documentid¼23188. [3] Fox HC, Bergquist KL, Hong KI, Synha R. Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals. Alcoholism: Clin Exp Res 2007; 31:395e403. [4] Besancon F. Time to alcohol dependence after abstinence and first drink. Addiction 1993;88:1647e1650.
Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clon.2011.04.010
Toxicity of Hypofractionated Accelerated Radiotherapy Concurrent with Chemotherapy for Non-small Cell Carcinoma of the Lung In terms of co-morbidity seven patients had previous COPD (chronic obstructive pulmonary disease), two had IHD (ischaemic heart disease), two had previous CVAs (cerebrovascular accidents), one had NIDDM (non insulin dependent diabetes mellitus), two had pulmonary fibrosis and two had alcohol excess. Toxicity was recorded during treatment and at 6 weeks, 3 months and 6 months. Acute toxicity data showed grade 3 oesophagitis affected 4/30 patients, grade 3 dyspnoea affected one patient and grade 3 lethargy affected one patient. The cumulative incidence of oesophagitis is detailed in Figure 1. Two patients had ongoing grade 2 oesophagitis at 6 months. Only four patients had modifications to their chemotherapy schedule. One patient missed their last fraction of radiotherapy. There were six admissions during and within 3 months after treatment (three patients with grade 3 oesophagitis, one patient with fluid overload, one patient with neutropenia and infection, one patient with tracheoesophageal fistula). There were no deaths within 3
Oesophagitis (cumulative toxicity) 18
Number of patients
Sir d We read with interest the recent debate on concurrent chemoradiotherapy for non-small cell lung cancer [1,2]. We would like to report our experience of treating non-small cell lung cancer with hypofractionated, accelerated radiotherapy and concurrent cisplatin/vinorelbine chemotherapy (SOCCAR regimen) in the Beatson West of Scotland Cancer Centre. A schedule of 55 Gy in 20 fractions is commonly used in the UK and has emerged on an empirical basis. However, there are sound radiobiological principles underlying the use of hypofractionated accelerated radiotherapy as accelerated repopulation occurs in non-small cell lung cancer [3]. Shortened radiotherapy regimens are cheaper and reduce treatment time for patients. There are, therefore, logical reasons for pursuing hypofractionated accelerated radiotherapy, despite current dogma for a prolonged 2 Gy per fraction regimen. SOCCAR was designed as a phase III trial examining arms of 55 Gy in 20 fractions with concurrent chemotherapy versus sequential neoadjuvant chemotherapy followed by radiotherapy. Recruitment was slow, due to concerns regarding potential toxicity and because of drift towards a prolonged 2 Gy per fraction schedule on the basis that this was used internationally. The trial was completed as a randomised phase II trial. Early results suggest impressive survival in both arms of the study. With regard to the tolerability of the concurrent 55 Gy in 20 schedule, we identified 30 patients who had been treated off study between 2005 and 2009. Radiotherapy was computed tomography planned, with a multifield technique concurrent with cisplatin 20 mg/m2 fractions 1e4 and 16e19, vinorelbine 15 mg/m2 fractions 1, 6, 15 and 20. Our population was Eastern Cooperative Oncology Group performance status 0 (21/30 patients) or 1 (9/30 patients). The median age was 64 years (39e74) and most patients were stage IIIA/B.
16 14 12 10 8 6 4 2 0 Grade 0/1
Grade 2
Grade 3
Fig. 1. Cumulative incidence of oesophagitis in patients treated with the soccar regime.
562
Letters / Clinical Oncology 23 (2011) 558e563
months of treatment. The long-term outcomes are being analysed. In conclusion, we have shown that accelerated hypofractionated radiotherapy concurrent with chemotherapy is a tolerable regimen. We feel it compares well with the reported toxicity of the concurrent regimen of 66 Gy in 33 fractions [1] and is worthy of consideration. R. Carruthers, N. O’Rourke, N. Mohammed, J. Hicks, I. Brisbane Beatson West of Scotland Cancer Centre, Glasgow, UK
References [1] O’Rourke N, MacBeth F. Is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2010;22:347e355. [2] Faivre Finn C, Le Pechoux C, Pignon JP, Auperin A. Reply to: is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2011;23:62e66. [3] Koukourakis M, Hlouverakis G, Kosma L, et al. The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys 1996;34:315e322.
Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clon.2011.05.006
Announcements
Clinical Oncology Editorial Board Vacancies Clinical Oncology is an international cancer journal covering all aspects of the clinical management of cancer patients, reflecting a multidisciplinary approach to therapy. We have a number of vacancies arising on the Editorial Board from November 2011 and applications for appointment to the Board are invited. Clinical Oncology has a broad remit, and representation from all areas of cancer management is sought on the Board including, oncology, haemato-oncology, pathology, surgical subspecialties, gynaecological oncology, palliative medicine, medical physics, cancer biology and radiobiology.
As a board member you would be expected to attend Board meetings held twice per year in May and November, to promote the journal within your field of practice, and to encourage submissions of high quality manuscripts from your colleagues. Board members would also be expected to take an active role in reviewing submitted manuscripts, and supporting the production of special issues of the journal within their sphere of interest. Interested candidates are asked to contact the Editorial office at email [email protected] for further details. CLOSING DATE FOR APPLICATIONS: FRIDAY, 30 SEPTEMBER 2011.
Joint Leeds/Mount Vernon Brachytherapy Course Thursday 24th November & Friday 25th November 2011 Mount Vernon Hospital, Northwood, Middlesex This course aims to give an overview of brachytherapy physics and techniques, with the emphasis on ‘how to do it’. It is particularly aimed at trainee oncologists, but is also open to physicists, dosimetrists and radiographers. Course Organisers: Dr C. Coyle, Leeds Prof P. Hoskin, Mount Vernon Further details: Emma Goddard, Royal College of Radiologists 38 Portland Place London W1N 4JQ Tel: 0207-636-4432 Ext 124 E-mail: [email protected]
should be informed, including the potential inability to drive. These precautions should also be taken with other drugs such as paclitaxel and etoposide. It might be worth undertaking a study measuring blood alcohol levels after infusion of these agents to determine if the legal limit of blood alcohol concentration for driving is frequently exceeded. Finally, the drug company should consider continuing the manufacture of docetaxel in its older formulation for the benefit of patients who cannot tolerate the high alcohol content. A. Mirza, N. Mithal Maidstone Hospital, Maidstone, UK
561
References [1] European Medicines Agency. Evaluation of medicines for human use, EMA/774985/2009. London: European Medicines Agency; 2009. [2] http://www.medicines.org.uk/EMC/pdfviewer.aspx?isAttachment¼ true&documentid¼23188. [3] Fox HC, Bergquist KL, Hong KI, Synha R. Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals. Alcoholism: Clin Exp Res 2007; 31:395e403. [4] Besancon F. Time to alcohol dependence after abstinence and first drink. Addiction 1993;88:1647e1650.
Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clon.2011.04.010
Toxicity of Hypofractionated Accelerated Radiotherapy Concurrent with Chemotherapy for Non-small Cell Carcinoma of the Lung In terms of co-morbidity seven patients had previous COPD (chronic obstructive pulmonary disease), two had IHD (ischaemic heart disease), two had previous CVAs (cerebrovascular accidents), one had NIDDM (non insulin dependent diabetes mellitus), two had pulmonary fibrosis and two had alcohol excess. Toxicity was recorded during treatment and at 6 weeks, 3 months and 6 months. Acute toxicity data showed grade 3 oesophagitis affected 4/30 patients, grade 3 dyspnoea affected one patient and grade 3 lethargy affected one patient. The cumulative incidence of oesophagitis is detailed in Figure 1. Two patients had ongoing grade 2 oesophagitis at 6 months. Only four patients had modifications to their chemotherapy schedule. One patient missed their last fraction of radiotherapy. There were six admissions during and within 3 months after treatment (three patients with grade 3 oesophagitis, one patient with fluid overload, one patient with neutropenia and infection, one patient with tracheoesophageal fistula). There were no deaths within 3
Oesophagitis (cumulative toxicity) 18
Number of patients
Sir d We read with interest the recent debate on concurrent chemoradiotherapy for non-small cell lung cancer [1,2]. We would like to report our experience of treating non-small cell lung cancer with hypofractionated, accelerated radiotherapy and concurrent cisplatin/vinorelbine chemotherapy (SOCCAR regimen) in the Beatson West of Scotland Cancer Centre. A schedule of 55 Gy in 20 fractions is commonly used in the UK and has emerged on an empirical basis. However, there are sound radiobiological principles underlying the use of hypofractionated accelerated radiotherapy as accelerated repopulation occurs in non-small cell lung cancer [3]. Shortened radiotherapy regimens are cheaper and reduce treatment time for patients. There are, therefore, logical reasons for pursuing hypofractionated accelerated radiotherapy, despite current dogma for a prolonged 2 Gy per fraction regimen. SOCCAR was designed as a phase III trial examining arms of 55 Gy in 20 fractions with concurrent chemotherapy versus sequential neoadjuvant chemotherapy followed by radiotherapy. Recruitment was slow, due to concerns regarding potential toxicity and because of drift towards a prolonged 2 Gy per fraction schedule on the basis that this was used internationally. The trial was completed as a randomised phase II trial. Early results suggest impressive survival in both arms of the study. With regard to the tolerability of the concurrent 55 Gy in 20 schedule, we identified 30 patients who had been treated off study between 2005 and 2009. Radiotherapy was computed tomography planned, with a multifield technique concurrent with cisplatin 20 mg/m2 fractions 1e4 and 16e19, vinorelbine 15 mg/m2 fractions 1, 6, 15 and 20. Our population was Eastern Cooperative Oncology Group performance status 0 (21/30 patients) or 1 (9/30 patients). The median age was 64 years (39e74) and most patients were stage IIIA/B.
16 14 12 10 8 6 4 2 0 Grade 0/1
Grade 2
Grade 3
Fig. 1. Cumulative incidence of oesophagitis in patients treated with the soccar regime.
562
Letters / Clinical Oncology 23 (2011) 558e563
months of treatment. The long-term outcomes are being analysed. In conclusion, we have shown that accelerated hypofractionated radiotherapy concurrent with chemotherapy is a tolerable regimen. We feel it compares well with the reported toxicity of the concurrent regimen of 66 Gy in 33 fractions [1] and is worthy of consideration. R. Carruthers, N. O’Rourke, N. Mohammed, J. Hicks, I. Brisbane Beatson West of Scotland Cancer Centre, Glasgow, UK
References [1] O’Rourke N, MacBeth F. Is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2010;22:347e355. [2] Faivre Finn C, Le Pechoux C, Pignon JP, Auperin A. Reply to: is concurrent chemoradiation the standard of care for locally advanced non-small cell lung cancer? A review of guidelines and evidence. Clin Oncol 2011;23:62e66. [3] Koukourakis M, Hlouverakis G, Kosma L, et al. The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys 1996;34:315e322.
Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clon.2011.05.006
Announcements
Clinical Oncology Editorial Board Vacancies Clinical Oncology is an international cancer journal covering all aspects of the clinical management of cancer patients, reflecting a multidisciplinary approach to therapy. We have a number of vacancies arising on the Editorial Board from November 2011 and applications for appointment to the Board are invited. Clinical Oncology has a broad remit, and representation from all areas of cancer management is sought on the Board including, oncology, haemato-oncology, pathology, surgical subspecialties, gynaecological oncology, palliative medicine, medical physics, cancer biology and radiobiology.
As a board member you would be expected to attend Board meetings held twice per year in May and November, to promote the journal within your field of practice, and to encourage submissions of high quality manuscripts from your colleagues. Board members would also be expected to take an active role in reviewing submitted manuscripts, and supporting the production of special issues of the journal within their sphere of interest. Interested candidates are asked to contact the Editorial office at email [email protected] for further details. CLOSING DATE FOR APPLICATIONS: FRIDAY, 30 SEPTEMBER 2011.
Joint Leeds/Mount Vernon Brachytherapy Course Thursday 24th November & Friday 25th November 2011 Mount Vernon Hospital, Northwood, Middlesex This course aims to give an overview of brachytherapy physics and techniques, with the emphasis on ‘how to do it’. It is particularly aimed at trainee oncologists, but is also open to physicists, dosimetrists and radiographers. Course Organisers: Dr C. Coyle, Leeds Prof P. Hoskin, Mount Vernon Further details: Emma Goddard, Royal College of Radiologists 38 Portland Place London W1N 4JQ Tel: 0207-636-4432 Ext 124 E-mail: [email protected]