Abstract
Oral Metronomic chemotherapy (OMC) is used in patients with lymphoma who may not tolerate intravenous chemotherapy or have refractory disease. It is cheaper, less toxic and easy to administer. Adult patients with lymphoma who received OMC (combination of cyclophosphamide, etoposide and prednisolone) were included in this retrospective analysis. Response assessment was clinical with limited use of radiology. Progression free and overall survival (PFS and OS) were calculated from the time of start of OMC until documentation of disease progression or death. Between 2007 and 2017, 149 patients were given OMC [median age: 62 years (19–87); 94 patients (63.1%) male]. Majority [112 patients (75.2%)] had stage III/IV disease. The most common subtype of lymphoma was diffuse large B cell lymphoma (40.9%). OMC was used at diagnosis in 41 patients (27.5%) and after relapse in 108 patients (72.5%). Overall response rates were 43.9 and 41.7% with clinical CR in 14 (34.1%) and 21 (19.4%) in patients given first line and later lines of OMC respectively. After a median follow up of 12 months (range 1–123 months), median PFS and OS were 10.5 (95% CI 8.6–12.5) and 18.8 (95% CI 12.1–25.5) months respectively. PFS and OS at 12 months were 47.6 and 64.2% respectively. Though OMC is used in many centers in India, there is scanty published information on its efficacy in lymphoma. In this analysis, we demonstrate its activity in a subset of patients with predominantly high-grade and advanced stage NHL. OMC is a useful option in frail patients and a small proportion can achieve deep and long lasting responses.
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References
Kerbel RS, Klement G, Pritchard KI, Kamen B (2002) Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol Off J Eur Soc Med Oncol 13(1):12–15
Browder T, Butterfield CE, Kräling BM, Shi B, Marshall B, O’Reilly MS et al (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60(7):1878–1886
Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105(8):1045–1047
André N, Banavali S, Snihur Y, Pasquier E (2013) Has the time come for metronomics in low-income and middle-income countries? Lancet Oncol 14(6):e239–e248
Fedele P, Marino A, Orlando L, Schiavone P, Nacci A, Sponziello F et al (2012) Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer. Eur J Cancer 48(1):24–29
Mir O, Domont J, Cioffi A, Bonvalot S, Boulet B, Le Pechoux C et al (2011) Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma. Eur J Cancer Oxf Engl 47(4):515–519
Gebbia V, Serretta V, Borsellino N, Valerio MR, GSTU Foundation (2011) Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel. Urology 78(5):1125–1130
Ang S-F, Tan S-H, Toh H-C, Poon DYH, Ong SYK, Foo K-F et al (2012) Activity of thalidomide and capecitabine in patients with advanced hepatocellular carcinoma. Am J Clin Oncol 35(3):222–227
Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R et al (2008) Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer 112(10):2228–2232
Ruan J, Martin P, Coleman M, Furman RR, Cheung K, Faye A et al (2010) Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma. Cancer 116(11):2655–2664
Buckstein R, Kerbel RS, Shaked Y, Nayar R, Foden C, Turner R et al (2006) High-dose celecoxib and metronomic “low-dose” cyclophosphamide is an effective and safe therapy in patients with relapsed and refractory aggressive histology non-Hodgkin’s lymphoma. Clin Cancer Res Off J Am Assoc Cancer Res 12(17):5190–5198
Zeng J, Yang L, Huang F et al (2016) The metronomic therapy with prednisone, etoposide, and cyclophosphamide reduces the serum levels of VEGF and circulating endothelial cells and improves responserates and progression-free survival in patients with relapsed or refractory non-Hodgkin lymphoma. Cancer Chemother Pharmacol 78(4):801–808
Ugocsai P, Wolff D, Menhart K et al (2016) Biomodulatory metronomic therapy induces PET-negative remission in chemo- and brentuximab-refractory Hodgkin lymphoma. Br J Haematol 172(2):290–293
Chen C-S, Doloff JC, Waxman DJ (2014) Intermittent metronomic drug schedule is essential for activating antitumor innate immunity and tumor xenograft regression. Neoplasia 16(1):84–96
Parikh PM, Hingmire SS, Deshmukh CD (2016) Selected current data on metronomic therapy (and its promise) from India. South Asian J Cancer 5(2):37–47
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Ms. Vanitha N for helping with collection of data.
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Mailankody, S., Ganesan, P., Joshi, A. et al. Outcomes of Oral Metronomic Therapy in Patients with Lymphomas. Indian J Hematol Blood Transfus 35, 50–56 (2019). https://doi.org/10.1007/s12288-018-0995-0
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DOI: https://doi.org/10.1007/s12288-018-0995-0