LG Gorenkova, EA Penskaya, SK Kravchenko, AM Kovrigina, TN Moiseeva, AI Vorob’ev
Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
For correspondence: Liliya Gamilevna Gorenkova, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; 8(495)612-23-61; e-mail: l.aitova@mail.ru
For citation: Gorenkova LG, Penskaya EA, Kravchenko SK, et al. Treatment of Drug-Resistant Mycosis Fungoides and Sezary Syndrome. Clinical oncohematology. 2017;10(3):366–71 (In Russ).
DOI: 10.21320/2500-2139-2017-10-3-366-371
ABSTRACT
Background. The most common diseases among cutaneous T-cell lymphomas are mycosis fungoides (MF) and its leukemic variant Sezary Syndrome (SS). These malignant tumors have a progressive character course. To date, no therapy for these diseases has proven effective, especially in the late stages of the disease.
Aim. We aimed to assess the effectiveness of treating resistant forms of MF/SS with prolonged gemcitabine regimen after initial treatment failure.
Materials & Methods. The study included 14 patients with drug-resistant forms of MF/SS (10 patients with MF, 3 patients with SS, and 1 patient with the transformation of MF into large cell lymphoma). The median age was 62 years (range 34–78 years). The study population included 9 males and 7 females. Gemcitabine was administered at a dosage of 250 mg/m2 as a 6–8 hour IV infusion weekly, in a cycle of 21–28 days.
Results. The overall response was 79 % (29 % of patients with complete remission, 50 % of patients with partial remission). In 21 % of patients, the treatment results met the criteria for tumor stabilization. The disease progression was observed in 2 (14 %) patients. This study demonstrates the potential of using prolonged gemcitabine regimen in patients of different age groups with advanced resistant MF/SS who received at least two courses of previous ineffective therapy. In order to evaluate long-term results, further research is needed.
Conclusion. The administration of prolonged gemcitabine regimen may be a treatment of choice in resistant forms of MF/SS after initial treatment failure in different age groups including elderly patients.
Keywords: mycosis fungoides, Sezary syndrome, treatment of drug-resistant forms, gemcitabine, prolonged infusion.
Received: December 6, 2016
Accepted: March 17, 2017
REFERENCES
- Виноградова Ю.Е., Потекаев Н.С., Виноградов Д.Л. Лимфомы кожи: диагностика и лечение. М.: Практическая медицина, 2014. 176 с.
[Vinogradova YuE, Potekaev NS, Vinogradov DL. Limfomy kozhi: diagnostika i lechenie. (Skin lymphomas: diagnosis and treatment.) Moscow: Prakticheskaya meditsina Publ.; 2014. 176 p. (In Russ)] - Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768–85. doi: 10.1182/blood-2004-09-3502.
- Olsen EA. Interferon in the treatment of cutaneous T-cell lymphoma. Dermatol Ther. 2003;16(4):311–21. doi: 10.1111/j.1396-0296.2003.01643.
- Zackheim HS, Kashani-Sabet M, McMillan A. Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol. 2003;49(5):873–8. doi: 10.1016/s0190-9622(03)01591-3.
- Wollina U, Dummer R, Brockmeyer NH, et al. Multicenter study of pegylated liposomal doxorubicin in therapy for cutaneous T-cell lymphoma. Cancer. 2003;98(5):993– doi: 10.1002/cncr.11593.
- Zhang C, Duvic M. Treatment of cutaneous T-cell lymphoma with retinoids. Dermatol Ther. 2006;19(5):264–71. doi: 10.1111/j.1529-8019.2006.00083.
- Molin L, Thomsen K, Volden G, et al. Combination chemotherapy in the tumor stage of mycosis fungoides with cyclophosphamide, vincristine, vp-16, adriamycin and prednisolone (COP, CHOP, CAVOP):a report fro the Scandinavian mycosis fungoides study group. Acta Derm Venereol. 1980;60(6):542–4.
- Duvic M, Apisarnthanarax N, Cohen DS, et al. Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2003;49(1):35–49. doi: 10.1067/mjd.2003.449.
- Hoppe RT, Harrison C, Tavallaee M, et al. Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase – II clinical trials. J Am Acad Dermatol. 2015;72(2):286–92. doi: 10.1016/j.jaad.2014.10.014.
- Zinzani PL, Baliva G, Magagnoli M, et al. Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol. 2000;18(13):2603–6. doi: 1200/jco.2000.18.13.2603.
- Marchi E, Alinari L, Tani M, et al. Gemcitabine as frontline treatment for cutaneous T cell lymphoma: phase II study of 32 patients. Cancer. 2005;104(11):2437–41. doi: 10.1002/cncr.21449.
- Duvic M, Talpur R, Wen S, et al. Phase II evaluation of gemcitabine monotherapy for cutaneous T-cell lymphoma. Clin Lymph Myel. 2006;7(1):51–8. doi: 10.3816/CLM.2006.n.039.
- Wu ZY, Guan HH, Lin ZX, et al. Combination of low-dose gemcitabine in 6-hour infusion and carboplatin is a favorable option for patients in poor performance status with advanced non-small cell lung cancer. J Chemother. 2014;26(5):306–11. doi: 10.1179/1973947813y.0000000139.
- Pollera CF, Ceribelli A, Crecco M, Oliva C. Prolonged infusion gemcitabine: a clinical phase I study at low- (300 mg/m2) and high-dose (875 mg/m2) levels. Invest New Drugs. 1997;15(2):115–21. doi: 10.1023/a:1005817024382.
- Maurel J, Zorrilla M, Puertolas T, et al. Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors. Anticancer Drugs. 2001;12(9):713–7. doi: 10.1097/00001813-200110000-00001.
- Akrivakis K, Schmid P, Flath B, et al. Prolonged infusion of gemcitabine in stage IV breast cancer. Anticancer Drugs. 1999;10(6):525–32. doi: 10.1097/00001813-199907000-00003.
- Von Delius S, Lersch Ch, Schulte-Frohlinde E, et al. Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma. BMC Cancer. 2005;5(1):61. doi: 10.1186/1471-2407-5-61.
- Eckel F, Schmelz R, Erdmann J, et al. Phase II trial of a 24-hour infusion of gemcitabine in previously untreated patients with advanced pancreatic adenocarcinoma. Cancer Invest. 2003;21(5):690–4. doi: 10.1081/cnv-120023767.
- Schmid P, Akrivakis K, Flath B, et al. A phase II trial of gemcitabine as prolonged infusion in metastatic breast cancer. Anticancer Drugs. 1999;10(7):625–31. doi: 10.1097/00001813-199908000-00001.
- Sezer O, Eucker J, Jakob C, et al. Achievement of complete remission in refractory Hodgkin’s disease with prolonged infusion of gemcitabine. Invest New Drugs. 2001;19(1):101–4.
- Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 85–91.
[Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders). Moscow: Buki Vedi Publ.; 2016. pp. 85–91. (In Russ)] - Olsen E, Vonderheid E, Pimpineli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110:1713–22. doi: 10.1182/blood-2008-02-142653.