- Email: [email protected]
Re: Han et al.
612
Letters / Clinical Oncology 28 (2016) 611e613
Febrile Neutropenia Rates in Men Treated with Docetaxel Chemotherapy for Metastatic Hormone-sensitive Prostate Cancer Madam d Recent clinical trials proving the benefit of docetaxel chemotherapy in hormone-sensitive metastatic prostate cancer (HSMPC) have reported a greater risk of febrile neutropenia than seen in the castrate-resistant setting. STAMPEDE [1] reported 15%, CHAARTED [2] 6% and GETUG-AFU15 [3] 7% grade 3e5 febrile neutropenia in comparison with Tax-327 [4], which showed 3% febrile neutropenia. Clinical experience at The Christie suggested the risk of febrile neutropenia was higher than that experienced in these trials. ASCO guidelines [5] recommend using colony stimulating factors (CSFs) prophylactically when the febrile neutropenia risk is 20%. An audit was conducted to establish febrile neutropenia rates in HSMPC patients referred to The Christie for docetaxel chemotherapy between 1 June 2015 and 1 February 2016. In total, 53 patients (all World Health Organization performance status 0/1) were eligible for inclusion. The median age was 65 years (range 43e79). The audit confirmed that 30% (16 of 53) of patients developed febrile neutropenia (defined as ANC <1.0, fever 37.5 C requiring admission and antibiotic treatment). Eighteen episodes of febrile neutropenia, involving 16 patients, were recorded with 12 episodes occurring after cycle 1. Ten did not complete the prescribed course of chemotherapy due to toxicity. Our findings suggest that patients receiving docetaxel in the HSMPC setting experience high rates of febrile neutropenia. We recommend the use of G-CSF from cycle 1 onwards when using docetaxel in the HSMPC setting. This is in keeping with findings from GETUG-AFU15, where after
four treatment-related deaths the use of G-CSF was mandated. We suggest that further work is required to investigate why men treated in the hormone-sensitive setting are much more likely to experience febrile neutropenia than in the hormone-resistant setting. J. Mahil*, C. Hughesy, K. Pately, J. Lyonsy, P.A. Elliotty, A. Choudhury*y, R. Conroyy * University of Manchester, Manchester, UK y The Christie Hospital NHS Foundation Trust, Manchester, UK
References [1] James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016;387:1163e1177. [2] Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. New Engl J Med 2015;373:737e746. [3] Gravis G, Fizazi K, Joly F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU15): a randomised, open-label, phase 3 trial. Lancet Oncol 2013;14:149e158. [4] Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisolone or mitoxantrone plus prednisolone for advanced prostate cancer. New Engl J Med 2004;351:1502e1512. [5] Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol 2015;33:3199e3212.
http://dx.doi.org/10.1016/j.clon.2016.06.006 Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Re: Han et al. Madam d It is with great interest that we read the recent manuscript from Han et al. [1] evaluating the impact of omitting radiotherapy in low-risk luminal A breast cancers. At a time when physicians are asked to provide value-based healthcare, analyses such as this can help shape policy and treatment decisions. However, there are concerns regarding this analysis; first is the failure to account for the costs of managing recurrences. Although rates of local recurrence are low, these costs must be included, as should an assessment of the quality of life and psychological impact of cancer recurrence, by using utilities rather than an absolute cost assessment. Previous studies have accounted for such factors and have shown radiotherapy to be cost-effective [2]. Additionally, the analysis looked at one radiotherapy regimen, hypofractionated whole breast irradiation using
either three-dimensional conformal radiotherapy or intensity-modulated radiation therapy. However, several alternative radiation techniques exist, including external beam accelerated partial breast irradiation or intraoperative radiation therapy, which can reduce the cost of radiotherapy [2,3]. Finally, the analysis assumed that patients not receiving radiation therapy took endocrine treatment. However, there are data that show high rates of noncompliance with endocrine therapy [4]. In addition, endocrine therapy can be associated with toxicities [e.g. blood clots, osteoporosis, hot flashes and even second malignancies (endometrial cancer/uterine sarcoma)] and the costs associated with its long-term administration cannot be ignored [5,6]. An alternative strategy may be to omit endocrine therapy in favour of radiotherapy in certain cases,
Letters / Clinical Oncology 28 (2016) 611e613
increasing compliance and potentially reducing toxicity without affecting costs (or potentially reducing them). It is clear that data such as those provided by Han et al. will help to shape future treatment decisions; however, we must remember to include all downstream costs. Finally, patient choice and informed decision making need to be respected rather than simply basing choices on an upfront absolute cost benefit. F. Vicini*, C. Shahy, C. Mantzz * 21st Century Oncology, Michigan Healthcare Professionals, Farmington Hills, MI, USA y Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA z 21st Century Oncology, Fort Myers, FL, USA
References
613
[2] Shah C, Badiyan S, Khwaja S, et al. Evaluating radiotherapy options in breast cancer: does intraoperative radiotherapy represent the most cost-efficacious option? Clin Breast Cancer 2014;14:141e146. [3] Shah C, Lanni TB, Saini H, et al. Cost-efficacy of acceleration partial-breast irradiation compared with whole breast irradiation. Breast Cancer Res Treat 2013;138:127e135. [4] Roberts MC, Wheeler SB, Reeder-Hayes K. Racial/ethnic and socioeconomic disparities in endocrine therapy adherence in breast cancer: a systematic review. Am J Public Health 2015;105:e4ee15. [5] Amir E, Seruga B, Niraula S, et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst 2011;103:1299e1309. [6] Nattinger AP, Pezzin LE, McGinley EL, et al. Patients costs of breast cancer endocrine therapy agents under Medicare Part D vs with general formulations. Springerplus 2015;4:54.
[1] Han K, Yap ML, Yong JHE, et al. Omission of breast radiotherapy in low-risk luminal A breast cancer: impact on health care costs. Clin Oncol 2016 Apr 29 [Epub ahead of print]. http://dx.doi.org/10.1016/j.clon.2016.05.007 Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Letters / Clinical Oncology 28 (2016) 611e613
Febrile Neutropenia Rates in Men Treated with Docetaxel Chemotherapy for Metastatic Hormone-sensitive Prostate Cancer Madam d Recent clinical trials proving the benefit of docetaxel chemotherapy in hormone-sensitive metastatic prostate cancer (HSMPC) have reported a greater risk of febrile neutropenia than seen in the castrate-resistant setting. STAMPEDE [1] reported 15%, CHAARTED [2] 6% and GETUG-AFU15 [3] 7% grade 3e5 febrile neutropenia in comparison with Tax-327 [4], which showed 3% febrile neutropenia. Clinical experience at The Christie suggested the risk of febrile neutropenia was higher than that experienced in these trials. ASCO guidelines [5] recommend using colony stimulating factors (CSFs) prophylactically when the febrile neutropenia risk is 20%. An audit was conducted to establish febrile neutropenia rates in HSMPC patients referred to The Christie for docetaxel chemotherapy between 1 June 2015 and 1 February 2016. In total, 53 patients (all World Health Organization performance status 0/1) were eligible for inclusion. The median age was 65 years (range 43e79). The audit confirmed that 30% (16 of 53) of patients developed febrile neutropenia (defined as ANC <1.0, fever 37.5 C requiring admission and antibiotic treatment). Eighteen episodes of febrile neutropenia, involving 16 patients, were recorded with 12 episodes occurring after cycle 1. Ten did not complete the prescribed course of chemotherapy due to toxicity. Our findings suggest that patients receiving docetaxel in the HSMPC setting experience high rates of febrile neutropenia. We recommend the use of G-CSF from cycle 1 onwards when using docetaxel in the HSMPC setting. This is in keeping with findings from GETUG-AFU15, where after
four treatment-related deaths the use of G-CSF was mandated. We suggest that further work is required to investigate why men treated in the hormone-sensitive setting are much more likely to experience febrile neutropenia than in the hormone-resistant setting. J. Mahil*, C. Hughesy, K. Pately, J. Lyonsy, P.A. Elliotty, A. Choudhury*y, R. Conroyy * University of Manchester, Manchester, UK y The Christie Hospital NHS Foundation Trust, Manchester, UK
References [1] James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016;387:1163e1177. [2] Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. New Engl J Med 2015;373:737e746. [3] Gravis G, Fizazi K, Joly F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU15): a randomised, open-label, phase 3 trial. Lancet Oncol 2013;14:149e158. [4] Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisolone or mitoxantrone plus prednisolone for advanced prostate cancer. New Engl J Med 2004;351:1502e1512. [5] Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol 2015;33:3199e3212.
http://dx.doi.org/10.1016/j.clon.2016.06.006 Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Re: Han et al. Madam d It is with great interest that we read the recent manuscript from Han et al. [1] evaluating the impact of omitting radiotherapy in low-risk luminal A breast cancers. At a time when physicians are asked to provide value-based healthcare, analyses such as this can help shape policy and treatment decisions. However, there are concerns regarding this analysis; first is the failure to account for the costs of managing recurrences. Although rates of local recurrence are low, these costs must be included, as should an assessment of the quality of life and psychological impact of cancer recurrence, by using utilities rather than an absolute cost assessment. Previous studies have accounted for such factors and have shown radiotherapy to be cost-effective [2]. Additionally, the analysis looked at one radiotherapy regimen, hypofractionated whole breast irradiation using
either three-dimensional conformal radiotherapy or intensity-modulated radiation therapy. However, several alternative radiation techniques exist, including external beam accelerated partial breast irradiation or intraoperative radiation therapy, which can reduce the cost of radiotherapy [2,3]. Finally, the analysis assumed that patients not receiving radiation therapy took endocrine treatment. However, there are data that show high rates of noncompliance with endocrine therapy [4]. In addition, endocrine therapy can be associated with toxicities [e.g. blood clots, osteoporosis, hot flashes and even second malignancies (endometrial cancer/uterine sarcoma)] and the costs associated with its long-term administration cannot be ignored [5,6]. An alternative strategy may be to omit endocrine therapy in favour of radiotherapy in certain cases,
Letters / Clinical Oncology 28 (2016) 611e613
increasing compliance and potentially reducing toxicity without affecting costs (or potentially reducing them). It is clear that data such as those provided by Han et al. will help to shape future treatment decisions; however, we must remember to include all downstream costs. Finally, patient choice and informed decision making need to be respected rather than simply basing choices on an upfront absolute cost benefit. F. Vicini*, C. Shahy, C. Mantzz * 21st Century Oncology, Michigan Healthcare Professionals, Farmington Hills, MI, USA y Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA z 21st Century Oncology, Fort Myers, FL, USA
References
613
[2] Shah C, Badiyan S, Khwaja S, et al. Evaluating radiotherapy options in breast cancer: does intraoperative radiotherapy represent the most cost-efficacious option? Clin Breast Cancer 2014;14:141e146. [3] Shah C, Lanni TB, Saini H, et al. Cost-efficacy of acceleration partial-breast irradiation compared with whole breast irradiation. Breast Cancer Res Treat 2013;138:127e135. [4] Roberts MC, Wheeler SB, Reeder-Hayes K. Racial/ethnic and socioeconomic disparities in endocrine therapy adherence in breast cancer: a systematic review. Am J Public Health 2015;105:e4ee15. [5] Amir E, Seruga B, Niraula S, et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst 2011;103:1299e1309. [6] Nattinger AP, Pezzin LE, McGinley EL, et al. Patients costs of breast cancer endocrine therapy agents under Medicare Part D vs with general formulations. Springerplus 2015;4:54.
[1] Han K, Yap ML, Yong JHE, et al. Omission of breast radiotherapy in low-risk luminal A breast cancer: impact on health care costs. Clin Oncol 2016 Apr 29 [Epub ahead of print]. http://dx.doi.org/10.1016/j.clon.2016.05.007 Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.