Radiotherapy and Oncology 112 (2014) 449–450
Contents lists available at ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Letter to the Editor Radiation-recall dermatitis with the everolimus/exemestane combination ten years after adjuvant whole-breast radiotherapy
The everolimus/exemestane combination is indicated for postmenopausal women with estrogen receptor (ER)-positive, HER2negative advanced breast cancer relapsing or progressing on non-steroidal aromatase inhibitors (NSAIs). Various adverse reactions (ARs) to this novel regimen have been described. To the best of our knowledge, we herein report the first case of radiation-recall dermatitis (RRD) in a breast-cancer patient, occurring ten years post adjuvant radiotherapy. A Caucasian 58-year-old female was diagnosed with a leftsided, early-stage, ER-positive, HER2-negative infiltrating lobular breast carcinoma in 2004. She was treated with breast-conserving surgery and conventional external-beam irradiation, followed by adjuvant tamoxifen for three years and then letrozole for another five years. In 2014, she relapsed with multiple hepatic and bone secondaries. Following a liver biopsy consistent with a metastatic ER-positive, HER2-negative ductal breast carcinoma, she received four cycles of adriamycin/cyclophosphamide, along with zoledronic acid. Despite symptom and liver-biochemical improvement, her disease remained stable by RECIST criteria, and she was offered maintenance letrozole for a three-month period, at the end of which, asymptomatic disease-progression was confirmed. In the absence of hepatic impairment, she was commenced on everolimus at the standard 10-mg daily dose plus exemestane, while continuing zoledronic acid. Three days later, she developed an acute, NCI-CTCAE v4 grade 2 RRD within the previously irradiated left-breast fields (Supplementary file; Fig. 1). The doublet regimen was withheld, while systemic corticosteroids were initiated, together with topical dexpanthenol. As the AR resolved completely over the following two weeks, corticosteroids were tapered off, and everolimus was resumed at 5 mg OD, combined with standard-dose exemestane. On treatment rechallenge, the RRD did not recur, but the patient developed a grade 2 oral mucositis and a mild, pruritic nasolabial erythema, both responding well to local measures only. She, therefore, continued on everolimus at half dose for two weeks to then be re-escalated to 10 mg OD, without any further mucocutaneous ARs. Radiation-recall phenomenon is an uncommon, unpredictable inflammatory reaction of unknown pathogenesis that is confined to previously irradiated sites, predominantly the skin, and can be precipitated by the administration of antineoplastic drugs, including cytotoxics, such as doxorubicin, and targeted agents [1]. Despite limited literature-reports of RRD induced by tamoxifen and NSAIs, to date, there is no data to suggest a similar triggering role for exemestane [1–3].
http://dx.doi.org/10.1016/j.radonc.2014.08.030 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
On the contrary, the radiosensitizing potential of everolimus is supported by preclinical and preliminary clinical evidence [4,5]. Nevertheless, concurrent palliative radiation was allowed in select pivotal clinical trials of the agent, and 70% of the BOLERO-2 study population had received radiotherapy [6]. Only two post-marketing, spontaneous cases of radiation recall have been published, both involving the gastrointestinal tract [7,8]. Furthermore, no recommendations are currently available on either dose-adjustment or rechallenge for the particular AR (AfinitorÒ EUSmPC; last rev. 12/2013). Therefore, our patient safety-report could have useful implications for breast-cancer care. It is the first case of RRD reported in association with the everolimus/exemestane combination. Interestingly, this developed shortly after the treatment initiation, but not during the prior administration of doxorubicin-based chemotherapy. It was successfully managed with temporary everolimus discontinuation and dose-modification, without recurrence on stepwise rechallenge. Disclosure The authors have declared no conflicts of interest. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.radonc.2014.0 8.030. References [1] Burris III HA, Hurtig J. Radiation recall with anticancer agents. Oncologist 2010;15:1227–37. [2] Haydaroglu A, Sert F, Kazandi AC, Unal I. Radiation recall reaction with anastrozole treatment in breast cancer. Pract Radiat Oncol 2012;2:65–8. [3] Foster LM, Mahoney ME, Harmon MW, Allen JW, Luh JY. Radiation recall reaction with letrozole therapy in breast cancer. Clin Breast Cancer 2014;14:95–7. [4] Albert JM, Kim KW, Cao C, Lu B. Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer. Mol Cancer Ther 2006;5:1183–9. [5] Ma D, Galanis E, Schiff D, et al. NCCTG N057K phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: a North Central Cancer Treatment Group trial. J Clin Oncol 2012;30(Suppl) [abstr 2031]. [6] Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther 2013;30:870–84. [7] Bourgier C, Massard C, Moldovan C, Soria JC, Deutsch E. Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent sideeffect? Ann Oncol 2011;22:485–6. [8] Miura Y, Suyama K, Shimomura A, et al. Radiation-induced esophagitis exacerbated by everolimus. Case Rep Oncol 2013;6:320–4.
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Letter to the Editor / Radiotherapy and Oncology 112 (2014) 449–450
Georgios Ioannidis Oncology Department, Nicosia General Hospital, 215, Nicosia-Limassol Old Ave., 2029 Strovolos, Nicosia, Cyprus E-mail addresses: [email protected], [email protected] Pinelopi Gkogkou Pandelitsa Charalampous Maria Diamandi Rena Ioannou Oncology Department, Nicosia General Hospital, Cyprus Received 27 July 2014 Accepted 11 August 2014 Available online 11 September 2014
Contents lists available at ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Letter to the Editor Radiation-recall dermatitis with the everolimus/exemestane combination ten years after adjuvant whole-breast radiotherapy
The everolimus/exemestane combination is indicated for postmenopausal women with estrogen receptor (ER)-positive, HER2negative advanced breast cancer relapsing or progressing on non-steroidal aromatase inhibitors (NSAIs). Various adverse reactions (ARs) to this novel regimen have been described. To the best of our knowledge, we herein report the first case of radiation-recall dermatitis (RRD) in a breast-cancer patient, occurring ten years post adjuvant radiotherapy. A Caucasian 58-year-old female was diagnosed with a leftsided, early-stage, ER-positive, HER2-negative infiltrating lobular breast carcinoma in 2004. She was treated with breast-conserving surgery and conventional external-beam irradiation, followed by adjuvant tamoxifen for three years and then letrozole for another five years. In 2014, she relapsed with multiple hepatic and bone secondaries. Following a liver biopsy consistent with a metastatic ER-positive, HER2-negative ductal breast carcinoma, she received four cycles of adriamycin/cyclophosphamide, along with zoledronic acid. Despite symptom and liver-biochemical improvement, her disease remained stable by RECIST criteria, and she was offered maintenance letrozole for a three-month period, at the end of which, asymptomatic disease-progression was confirmed. In the absence of hepatic impairment, she was commenced on everolimus at the standard 10-mg daily dose plus exemestane, while continuing zoledronic acid. Three days later, she developed an acute, NCI-CTCAE v4 grade 2 RRD within the previously irradiated left-breast fields (Supplementary file; Fig. 1). The doublet regimen was withheld, while systemic corticosteroids were initiated, together with topical dexpanthenol. As the AR resolved completely over the following two weeks, corticosteroids were tapered off, and everolimus was resumed at 5 mg OD, combined with standard-dose exemestane. On treatment rechallenge, the RRD did not recur, but the patient developed a grade 2 oral mucositis and a mild, pruritic nasolabial erythema, both responding well to local measures only. She, therefore, continued on everolimus at half dose for two weeks to then be re-escalated to 10 mg OD, without any further mucocutaneous ARs. Radiation-recall phenomenon is an uncommon, unpredictable inflammatory reaction of unknown pathogenesis that is confined to previously irradiated sites, predominantly the skin, and can be precipitated by the administration of antineoplastic drugs, including cytotoxics, such as doxorubicin, and targeted agents [1]. Despite limited literature-reports of RRD induced by tamoxifen and NSAIs, to date, there is no data to suggest a similar triggering role for exemestane [1–3].
http://dx.doi.org/10.1016/j.radonc.2014.08.030 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
On the contrary, the radiosensitizing potential of everolimus is supported by preclinical and preliminary clinical evidence [4,5]. Nevertheless, concurrent palliative radiation was allowed in select pivotal clinical trials of the agent, and 70% of the BOLERO-2 study population had received radiotherapy [6]. Only two post-marketing, spontaneous cases of radiation recall have been published, both involving the gastrointestinal tract [7,8]. Furthermore, no recommendations are currently available on either dose-adjustment or rechallenge for the particular AR (AfinitorÒ EUSmPC; last rev. 12/2013). Therefore, our patient safety-report could have useful implications for breast-cancer care. It is the first case of RRD reported in association with the everolimus/exemestane combination. Interestingly, this developed shortly after the treatment initiation, but not during the prior administration of doxorubicin-based chemotherapy. It was successfully managed with temporary everolimus discontinuation and dose-modification, without recurrence on stepwise rechallenge. Disclosure The authors have declared no conflicts of interest. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.radonc.2014.0 8.030. References [1] Burris III HA, Hurtig J. Radiation recall with anticancer agents. Oncologist 2010;15:1227–37. [2] Haydaroglu A, Sert F, Kazandi AC, Unal I. Radiation recall reaction with anastrozole treatment in breast cancer. Pract Radiat Oncol 2012;2:65–8. [3] Foster LM, Mahoney ME, Harmon MW, Allen JW, Luh JY. Radiation recall reaction with letrozole therapy in breast cancer. Clin Breast Cancer 2014;14:95–7. [4] Albert JM, Kim KW, Cao C, Lu B. Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer. Mol Cancer Ther 2006;5:1183–9. [5] Ma D, Galanis E, Schiff D, et al. NCCTG N057K phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: a North Central Cancer Treatment Group trial. J Clin Oncol 2012;30(Suppl) [abstr 2031]. [6] Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther 2013;30:870–84. [7] Bourgier C, Massard C, Moldovan C, Soria JC, Deutsch E. Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent sideeffect? Ann Oncol 2011;22:485–6. [8] Miura Y, Suyama K, Shimomura A, et al. Radiation-induced esophagitis exacerbated by everolimus. Case Rep Oncol 2013;6:320–4.
450
Letter to the Editor / Radiotherapy and Oncology 112 (2014) 449–450
Georgios Ioannidis Oncology Department, Nicosia General Hospital, 215, Nicosia-Limassol Old Ave., 2029 Strovolos, Nicosia, Cyprus E-mail addresses: [email protected], [email protected] Pinelopi Gkogkou Pandelitsa Charalampous Maria Diamandi Rena Ioannou Oncology Department, Nicosia General Hospital, Cyprus Received 27 July 2014 Accepted 11 August 2014 Available online 11 September 2014
