- Email: [email protected]
Concurrent radiation therapy and bortezomib in myeloma patient
Letters to the Editor / Radiotherapy and Oncology 86 (2008) 285–292
291
Fig. 1. Sacral lesion before (A) and after treatment (B). (A) Axial T1 weighted sequence with fat saturation before treatment. The left sacrum wings showed a huge vascularised lesion (arrow). (B) Axial T1 weighted sequence with image subtraction between pre and post Gadolinium chelate injection. The lesion its stable in size and showed an important decrease in vascularisation with persistent contrast uptake on is medial portion (arrow).
significant responses in about a third of treated patients with relapsed/refractory disease [1]. Preclinical and clinical data have shown that bortezomib enhanced sensitivity and reversed resistance to standard therapeutic agents used in MM, such as dexamethasone [2]. We report here the second MM patient treated by concurrent radiation therapy (RT) and bortezomib [3]. In December 2004, a male patient 61 years old was diagnosed as having stage IIIa IgG.j MM with compressive T3 vertebra mass. A decompressive surgery and local radiotherapy were first realised, followed by a first line VAD (vincristine/ doxorubicin/dexamethasone) chemotherapy regimen and high-dose Melphalan + autologous stem cell transplantation (ASCT). Because of a biological increase of the monoclonal component before ASCT, thalidomide was then introduced. Despite a first response to thalidomide, the dose should be decreased because of the occurrence of a grade 3 neuropathy. Therefore, after 15 months of thalidomide administration, a second biological recurrence occurred. A new treatment was then proposed to the patient as bortezomib administration at a dosage of 1.3 mg/m2 at days 1, 4, 8, 11 every 3 weeks plus dexamethasone 40 mg at days 1–4. Magnetic resonance imaging (MRI) and 18FDG-PET/CT showed a lytic lesion of the sacrum (Fig. 1A). A localized RT was realised using 10 MV photons at a total dose of 30 Gy in 10 fractions with concomitantly third and fourth courses of bortezomib treatment. During radiotherapy, the patient experienced one grade 1 diarrhoea episode without haematological or skin toxicities. Ten days after RT, the patient presented grade 3 diarrhoea and an increased fatigue. As the treatment should be discontinued for ten days, neither hospitalisation nor intensive cares have been required. At 16 weeks from RT, the patient is RTOG 1 with stable disease, as shown on a new MRI (Fig. 1B). Proteasome inhibitors have been reported to enhance radiosensitivity in vitro [1]. The first case reported in the literature showed unexpected and severe acute radiation
enteritis requiring hospital admission [1]. Similarly, few other cases of gastrointestinal (GI) toxicity have been reported in patients treated by bortezomib alone [4,5]. In contrast, our case of concurrent bortezomib and radiation therapy showed an acceptable GI tolerance, suggesting that more experiences are therefore warranted to confirm our observation. However, in case of concurrent bortezomib administration and radiotherapy, a special care should be taken to GI organs localized in the field of irradiation that could require an adapted dose and fractionation of the RT protocol.
References [1] Laura R, Cibeira MT, Uriburu C, et al. Bortezomib: an effective agent in extramedullary disease in multiple myeloma. Eur J Haematol 2006;76:405–8. [2] Blade J, Cibeira MT, Rosin ˜ol L. Bortezomib: a valuable new antineoplastic strategy in multiple myeloma. Acta Oncol 2005;44:440–8. [3] Mohiuddin MM, Harmon DC, Delaney TF. Severe acute enteritis in a multiple myeloma patient receiving bortezomib and spinal radiotherapy: case report. J Chemother 2005;17:343–6. [4] Perfetti V, Palladini G, Brunetti L, et al. Bortezomib-induced paralytic ileus is a potential gastrointestinal side effect of this first-in-class anticancer proteasome inhibitor. Eur J Gastroenterol Hepatol 2007;19:599–601. [5] Moon SJ, Min CK, Lee DG, et al. Pseudomembranous colitis following bortezomib therapy in a myeloma patient. Acta Haematol 2007;117:211–4.
Oscar Berges Radiation Oncology, Institut Curie, Paris, France Didier Decaudin Hematology, Institut Curie, Paris, France Vincent Servois Radiology, Institut Curie, Paris, France
292
Letters to the Editor / Radiotherapy and Oncology 86 (2008) 285–292
Youlia M. Kirova* Radiation Oncology, Institut Curie, 26, Rue d’Ulm, 75005 Paris, France E-mail addresses: [email protected] Received 10 December 2007; accepted 11 December 2007;
Available online 15 January 2008 *
Corresponding author.
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2007.12.015
291
Fig. 1. Sacral lesion before (A) and after treatment (B). (A) Axial T1 weighted sequence with fat saturation before treatment. The left sacrum wings showed a huge vascularised lesion (arrow). (B) Axial T1 weighted sequence with image subtraction between pre and post Gadolinium chelate injection. The lesion its stable in size and showed an important decrease in vascularisation with persistent contrast uptake on is medial portion (arrow).
significant responses in about a third of treated patients with relapsed/refractory disease [1]. Preclinical and clinical data have shown that bortezomib enhanced sensitivity and reversed resistance to standard therapeutic agents used in MM, such as dexamethasone [2]. We report here the second MM patient treated by concurrent radiation therapy (RT) and bortezomib [3]. In December 2004, a male patient 61 years old was diagnosed as having stage IIIa IgG.j MM with compressive T3 vertebra mass. A decompressive surgery and local radiotherapy were first realised, followed by a first line VAD (vincristine/ doxorubicin/dexamethasone) chemotherapy regimen and high-dose Melphalan + autologous stem cell transplantation (ASCT). Because of a biological increase of the monoclonal component before ASCT, thalidomide was then introduced. Despite a first response to thalidomide, the dose should be decreased because of the occurrence of a grade 3 neuropathy. Therefore, after 15 months of thalidomide administration, a second biological recurrence occurred. A new treatment was then proposed to the patient as bortezomib administration at a dosage of 1.3 mg/m2 at days 1, 4, 8, 11 every 3 weeks plus dexamethasone 40 mg at days 1–4. Magnetic resonance imaging (MRI) and 18FDG-PET/CT showed a lytic lesion of the sacrum (Fig. 1A). A localized RT was realised using 10 MV photons at a total dose of 30 Gy in 10 fractions with concomitantly third and fourth courses of bortezomib treatment. During radiotherapy, the patient experienced one grade 1 diarrhoea episode without haematological or skin toxicities. Ten days after RT, the patient presented grade 3 diarrhoea and an increased fatigue. As the treatment should be discontinued for ten days, neither hospitalisation nor intensive cares have been required. At 16 weeks from RT, the patient is RTOG 1 with stable disease, as shown on a new MRI (Fig. 1B). Proteasome inhibitors have been reported to enhance radiosensitivity in vitro [1]. The first case reported in the literature showed unexpected and severe acute radiation
enteritis requiring hospital admission [1]. Similarly, few other cases of gastrointestinal (GI) toxicity have been reported in patients treated by bortezomib alone [4,5]. In contrast, our case of concurrent bortezomib and radiation therapy showed an acceptable GI tolerance, suggesting that more experiences are therefore warranted to confirm our observation. However, in case of concurrent bortezomib administration and radiotherapy, a special care should be taken to GI organs localized in the field of irradiation that could require an adapted dose and fractionation of the RT protocol.
References [1] Laura R, Cibeira MT, Uriburu C, et al. Bortezomib: an effective agent in extramedullary disease in multiple myeloma. Eur J Haematol 2006;76:405–8. [2] Blade J, Cibeira MT, Rosin ˜ol L. Bortezomib: a valuable new antineoplastic strategy in multiple myeloma. Acta Oncol 2005;44:440–8. [3] Mohiuddin MM, Harmon DC, Delaney TF. Severe acute enteritis in a multiple myeloma patient receiving bortezomib and spinal radiotherapy: case report. J Chemother 2005;17:343–6. [4] Perfetti V, Palladini G, Brunetti L, et al. Bortezomib-induced paralytic ileus is a potential gastrointestinal side effect of this first-in-class anticancer proteasome inhibitor. Eur J Gastroenterol Hepatol 2007;19:599–601. [5] Moon SJ, Min CK, Lee DG, et al. Pseudomembranous colitis following bortezomib therapy in a myeloma patient. Acta Haematol 2007;117:211–4.
Oscar Berges Radiation Oncology, Institut Curie, Paris, France Didier Decaudin Hematology, Institut Curie, Paris, France Vincent Servois Radiology, Institut Curie, Paris, France
292
Letters to the Editor / Radiotherapy and Oncology 86 (2008) 285–292
Youlia M. Kirova* Radiation Oncology, Institut Curie, 26, Rue d’Ulm, 75005 Paris, France E-mail addresses: [email protected] Received 10 December 2007; accepted 11 December 2007;
Available online 15 January 2008 *
Corresponding author.
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2007.12.015