De-escalating cancer treatments during COVID 19 pandemic: Is metronomic chemotherapy a reasonable option?

Addeo, 2008, Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for non-small cell lung cancer and breast cancer patients with brain metastases, Cancer, 113, 2524, 10.1002/cncr.23859 Addeo, 2010, Low-dose metronomic oral administration of vinorelbine in the first-line treatment of elderly patients with metastatic breast cancer, Clin. Breast Cancer, 10, 301, 10.3816/CBC.2010.n.039 Alagizy, 2015, Metronomic capecitabine as extended adjuvant chemotherapy in women with triple negative breast cancer, Hematol. Oncol. Stem Cell Ther., 8, 22, 10.1016/j.hemonc.2014.11.003 Alvarez, 1999, The prognostic significance of angiogenesis in epithelial ovarian carcinoma, Clin. Cancer Res., 5, 587 Aurilio, 2012, Oral metronomic cyclophosphamide and methotrexate plus fulvestrant in advanced breast cancer patients: a mono-institutional case-cohort report, Breast J., 18, 470, 10.1111/j.1524-4741.2012.01278.x Banna, 2017, Palliative chemotherapy with oral metronomic vinorelbine in advanced non-small cell lung cancer (NSCLC) patients unsuitable for chemotherapy, J. Thorac. Oncol., 12, S907, 10.1016/j.jtho.2016.11.1241 Barroso-Sousa, 2015, Metronomic oral cyclophosphamide plus prednisone in docetaxel pretreated patients with metastatic castration-resistant prostate cancer, Med. Oncol., 32, 443, 10.1007/s12032-014-0443-4 Beck, 1968, Treatment of 126 cases of advanced ovarian carcinoma with cyclophosphamide, Can. Med. Assoc. J., 98, 539 Bellmunt, 2010, Activity of a multitargeted chemo-switch regimen (sorafenib, gemcitabine, and metronomic capecitabine) in metastatic renal-cell carcinoma: a phase 2 study (SOGUG-02-06), Lancet Oncol., 11, 350, 10.1016/S1470-2045(09)70383-3 Bhatt, 2010, A phase 2 pilot trial of low-dose, continuous infusion, or ‘metronomic’ paclitaxel and oral celecoxib in patients with metastatic melanoma, Cancer, 116, 1751, 10.1002/cncr.24902 Bhattacharyya, 2017, Phase II study of metronomic cyclophosphamide and temozolomide in platinum resistance ovarian cancer. ASCO Annual Meeting Proceedings, J. Clin. Oncol., 33, e16575 Bilir, 2017, Efficacy of metronomic vinorelbine in elderly patients with advanced non-small-cell lung cancer and poor performance status, Curr. Oncol., 24, e199, 10.3747/co.24.3486 Borgonovo, 2016, Monoinstitutional retrospective analysis of metronomic capecitabine (mc) schedule in the treatment of metastatic colorectal cancer European Society for Medical Oncology Congress Proceedings, Ann. Oncol., 27, D48 Borne, 2010, Oral metronomic cyclophosphamide in elderly with metastatic melanoma, Investig. New Drugs, 28, 684, 10.1007/s10637-009-9298-5 Bracarda, 2000, Oral estramustine and cyclophosphamide in patients with metastatic hormone refractory prostate carcinoma: a phase II study, Cancer, 88, 1438, 10.1002/(SICI)1097-0142(20000315)88:6<1438::AID-CNCR23>3.0.CO;2-O Budman, 1998, Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine, J. Clin. Oncol., 16, 1795, 10.1200/JCO.1998.16.5.1795 Caffo, 2019, Activity and safety of metronomic cyclophosphamide in the modern era of metastatic castration-resistant prostate cancer, Future Oncol., 15, 1115, 10.2217/fon-2018-0715 Calcagno, 2016, Metronomic cyclophosphamide therapy in hormone-naive patients withnon-metastatic biochemical recurrent prostate cancer: a phase II trial, Med. Oncol., 33, 8, 10.1007/s12032-016-0806-0 Calvan iN, 2019, Metronomic chemotherapy with cyclophosphamide plus low dose of corticosteroids in advanced castration-resistant prostate cancer across the era of taxanes and new hormonal drugs, Med. Oncol., 36, 80, 10.1007/s12032-019-1304-y Camerini, 2015, Metronomic oral vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer: results of a phase II trial (MOVE trial), BMC Cancer, 15, 1, 10.1186/s12885-015-1354-2 Carreca, 2011, Metronomic (M), capecitabine (C), and oxaliplatin (O) plus bevacizumab (B) as treatment of advanced colorectal cancer (ACRC) in very elderly people (M-COB): efficacy and safety (E&S) evaluation-A 2-year monitoring. ASCO Annual Meeting Proceedings, J. Clin. Oncol., 29, e14086, 10.1200/jco.2011.29.15_suppl.e14086 Cazzaniga, 2014, Efficacy and safety of the all-oral schedule of metronomic vinorelbine and capecitabine in locally advanced or metastatic breast cancer patients: the Phase I-II VICTOR-1 Study, Int. J. Breast Cancer, 769 Cazzaniga, 2016, Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study, Breast Cancer Res. Treat., 160, 501, 10.1007/s10549-016-4009-3 Chen, 2013, The efficacy of temozolomide for recurrent glioblastoma multiforme, Eur. J. Neurol., 20, 223, 10.1111/j.1468-1331.2012.03778.x Chura, 2007, Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer, Gynecol. Oncol., 107, 326, 10.1016/j.ygyno.2007.07.017 Clarke, 2009, Randomized phase II trial of chemoradiotherapy followed by either dose-dense metronomic temozolomide for newly diagnosed glioblastoma, J. Clin. Oncol., 27, 3861, 10.1200/JCO.2008.20.7944 Colleoni, 2002, Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels, Ann. Oncol., 13, 73, 10.1093/annonc/mdf013 Colleoni, 2006, A Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects, Ann. Oncol., 17, 232, 10.1093/annonc/mdj066 Colleoni, 2016, Low-dose oral cyclophosphamide and methotrexate maintenance for hormone receptor-negative early breast cancer: International Breast Cancer Study Group Trial 22-00, J. Clin. Oncol., 34, 3400, 10.1200/JCO.2015.65.6595 Correale, 2006, A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients, Oncol. Rep., 16, 133 Cremolini, 2019, Phase II randomized study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial, Eur. J. Cancer, 109, 175, 10.1016/j.ejca.2018.12.028 D’Ascanio, 2018, Metronomic chemotherapy with vinorelbine produces clinical benefit and low toxicity in frail elderly patients affected by advanced non-small cell lung cancer, Biomed. Res. Int., 27, 1, 10.1155/2018/6278403 Dabkara, 2018, Metronomic cyclophosphamide in metastatic castrate resistant prostate cancer: experience from a tertiary cancer care center, Indian J. Cancer, 55, 94, 10.4103/ijc.IJC_346_17 De Iuliis, 2015, On and off metronomic oral vinorelbine in elderly women with advanced breast cancer, Tumori, 101, 30, 10.5301/tj.5000207 De la Haba, 2015, Randomised phase II study evaluating, as first-line chemotherapy, single-agent oral vinorelbine administered with two different schedules in patients with hormone receptor positive, HER2-negative advanced breast cancer (TempoBreast-1 trial) Dellapasqua, 2008, Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer, J. Clin. Oncol., 26, 4899, 10.1200/JCO.2008.17.4789 Derosa, 2014, Docetaxel plus oral metronomic cyclophosphamide: a phase II study with pharmacodynamic and pharmacogenetic analyses in castrationresistant prostate cancer patients, Cancer, 120, 3923, 10.1002/cncr.28953 Di Desidero, 2016, Clinical, pharmacodynamic and pharmacokinetic results of a prospective phase II study on oral metronomic vinorelbine and dexamethasone in castration-resistant prostate cancer patients, Investig. New Drugs, 34, 760, 10.1007/s10637-016-0385-0 Eek, 2016, Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature, Patient Prefer Adher., 10, 1609, 10.2147/PPA.S106629 Ellebaek, 2012, Metastatic melanoma patients treated with dendritic cell vaccination. Interleukin-2 and metronomic cyclophosphamide: results from a phase II trial, Cancer Immunol. Immunother., 61, 1791, 10.1007/s00262-012-1242-4 Fea, 2016, Metronomic oral cyclophosphamide (CTX) in patients (pts) with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), European Society for Medical Oncology Congress Proceedings, Ann. Oncol., 2016, iv38, 10.1093/annonc/mdw334.29 Fedele, 2012, Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer, Eur. J. Cancer, 48, 24, 10.1016/j.ejca.2011.06.040 Ferrandina, 2014, Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients: a retrospective, multicenter study, BMC Cancer, 14, 1, 10.1186/1471-2407-14-947 Fontana, 2009, Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer, Clin. Cancer Res., 15, 4954, 10.1158/1078-0432.CCR-08-3317 Garcia, 2008, Phase II clinical trial of bevacizumab and low-dosemetronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia, J. Clin. Oncol., 26, 76, 10.1200/JCO.2007.12.1939 Garcia-Saenz, 2008, Bevacizumab in combinationwith metronomic chemotherapy in patients with anthracycline- and taxane-refractory breast cancer, J. Chemother., 20, 632, 10.1179/joc.2008.20.5.632 Gebbia, 2011, Salvage therapy with oral metronomic cyclophosphamide andmethotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel, Urology, 78, 1125, 10.1016/j.urology.2011.08.010 Glode, 2003, Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma, Cancer, 98, 1643, 10.1002/cncr.11713 Hanahan, 2000, Less is more, regularly: metronomic dosing of cytotoxic drugs can target can target tumour angiogenesis in mice, J. Clin. Investig., 105, 1045, 10.1172/JCI9872 Handolias, 2016, Oral cyclophosphamide in recurrent ovarian cancer, Asia Pac. J. Clin. Oncol., 12, e154, 10.1111/ajco.12074 Hashimoto, 2010, Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer, Mol Cancer Ther., 9, 996, 10.1158/1535-7163.MCT-09-0960 Hatano, 2011, Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer, Jpn. J. Clin. Oncol., 41, 253, 10.1093/jjco/hyq178 Hellerstedt, 2003, Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma, Cancer, 98, 1603, 10.1002/cncr.11686 Jedeszko, 2015, Postsurgical adjuvant or metastatic renal cell carcinoma therapy models reveal potent antitumor activity of metronomic oral topotecan with pazopanib, Sci. Transl. Med., 7, 282ra50, 10.1126/scitranslmed.3010722 Jellvert, 2011, Effective oral combination metronomic chemotherapy with low toxicity for the management of castration-resistant prostate cancer, Exp. Therapeut. Med., 2, 579, 10.3892/etm.2011.272 Jeong, 2017, Efficacy of metronomic oral cyclophosphamide with low dose dexamethasone and celecoxib in metastatic castration-resistant prostate cancer, Asia-Pac. J. Clin. Oncol., 13, 204, 10.1111/ajco.12583 Jurado, 2008, Combined oral cyclophosphamide and bevacizumab in heavily pre-treatedovarian cancer, Clin. Transl. Oncol., 10, 583, 10.1007/s12094-008-0254-7 Kakolyris, 1998, Treatment of non-small-cell lung cancer with prolonged oral etoposide, Am. J. Clin. Oncol., 21, 505, 10.1097/00000421-199810000-00018 Kamat, 2007, Metronomic chemotherapy enhances the efficacy of antivascular therapy in ovarian cancer, Cancer Res., 67, 281, 10.1158/0008-5472.CAN-06-3282 Katsaounis, 2015, Cisplatin in combination with metronomic vinorelbine as front-line treatment in advanced non-small cell lung cancer: a multicenter phase II study of the hellenic oncology research group (HORG), Cancer Chemother. Pharmacol., 75, 821, 10.1007/s00280-015-2707-x Kerbel, 2007, Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs, Cancer Res Treat, 39, 150, 10.4143/crt.2007.39.4.150 Kesari, 2007, Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults, Neuro-oncology, 9, 354, 10.1215/15228517-2007-006 Khan, 2011, Continuous low dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer, Br. J. Cancer, 104, 1822, 10.1038/bjc.2011.154 Kong, 2010, Phase II trial of low dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma, Neuro-oncology, 12, 289, 10.1093/neuonc/nop030 Kontopodis, 2013, A phase II study of metronomic oral vinorelbine administered in the second line and beyond in non-small cell lung cancer (NSCLC): a phase II study of the hellenic oncology research group, J. Chemother., 25, 49, 10.1179/1973947812Y.0000000050 Kouroussis, 2009, Continuous administration of daily low-dose temozolomide in pretreated patients with advanced non-small cell lung cancer: a phase II study, Oncology, 76, 112, 10.1159/000192586 Kucukoner, 2012, Oral etoposide for platinum-resistant and recurrent epithelial ovarian cancer: a study by the anatolian society of medical oncology, Asian Pac. J. Cancer Prev., 13, 3973, 10.7314/APJCP.2012.13.8.3973 Ladoire, 2010, Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure, Anticancer Res., 30, 4317 Lambertini, 2020, Cancer care during the spread of coronavirus disease 2019 (COVID-19) in Italy: young oncologists’ perspective, ESMO Open, 5, 10.1136/esmoopen-2020-000759 Langkjer, 2019, The NAME trial: a direct comparison of classical oral Navelbine versus Metronomic Navelbine in metastatic breast cancer, Future Oncol., 15, 2561, 10.2217/fon-2019-0124 Liang, 2020, Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China, Lancet Oncol., 21, 335, 10.1016/S1470-2045(20)30096-6 Lokich, 2004, Capecitabine: fixed daily dose and continuous (noncyclic) dosing schedule, Cancer Investig., 22, 713, 10.1081/CNV-200032976 Lord, 2007, Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study, J. Urol., 177, 2136, 10.1016/j.juro.2007.01.143 Metronomic Chemotherapy of Capecitabine after Standard Adjuvant Chemotherapy in Operable Triple Negative Breast Cancer (MACRO). ClinicalTrials.gov Identifier: NCT02012634. Markman, 1992, Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum refractory ovarian cancer, J. Cancer Res. Clin. Oncol., 119, 55, 10.1007/BF01209489 Maulard-Durdux, 1996, Phase II study of the oral cyclophosphamide and oral etoposide combination in hormone refractory prostate carcinoma patients, Cancer, 77, 1144, 10.1002/(SICI)1097-0142(19960315)77:6<1144::AID-CNCR21>3.0.CO;2-0 Mayer, 2012, Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics, Breast Cancer Res. Treat., 136, 169, 10.1007/s10549-012-2256-5 Mayer, 2016, TBCRC 012L ABCDE, a phase II randomized study of adjuvant bevacizumab, metronomic chemotherapy (CM), diet and exercise after preoperative chemotherapy for breast cancer. ASCO Annual Meeting Proceedings, J. Clin. Oncol., 28, 103 Mencoboni, 2017, Safety of first-line chemotherapy with metronomic single-agent oral vinorelbine in elderly patients with NSCLC, Anticancer Res., 37, 3189 Meng, 2012, Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plusthalidomide and prednisone in prostate cancer patients, J. Cancer Res. Clin. Oncol., 138, 333, 10.1007/s00432-011-1101-2 MEtronomicTrEatment Option in Advanced bReastcAncer (METEORA-II). ClinicalTrials.gov Identifier: NCT02954055. Montagna, 2012, Metronomic chemotherapy combined with bevacizumab and erlotinib in patients with metastatic HER2-negative breast cancer: clinical and biological activity, Clin. Breast Cancer, 12, 207, 10.1016/j.clbc.2012.03.008 Montagna, 2018, Metronomic chemotherapy for first-line treatment of metastatic triple-negative breast cancer: a phase II trial, Breast Care, 13, 177, 10.1159/000487630 Muraki, 2012, Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells, Int. J. Cancer, 130, 59, 10.1002/ijc.25976 Nasr, 2015, Metronomic methotrexate and cyclophosphamide after carboplatin included adjuvant chemotherapy in triple negative breast cancer: a phase III study, Ann. Transl. Med., 3, 284 Nelius, 2010, Clinical outcome of patients with docetaxel-resistant hormone- refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy, Med. Oncol., 27, 363, 10.1007/s12032-009-9218-8 2020 Nishimura, 2001, Oral combination of cyclophosphamide, uracil plus tegafur and estramustine for hormone-refractory prostate cancer, Oncology, 60, 49, 10.1159/000055296 Noronha, 2016, Health-related quality of life in patients with metastatic, relapsed, or inoperable squamous cell carcinoma of the head and neck in India, Support. Care Cancer, 24, 1595, 10.1007/s00520-015-2937-9 Omuro, 2013, Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma, Neuro-oncology, 15, 242, 10.1093/neuonc/nos295 Ontario Health, Cancer Care Ontario, 2020 Orlando, 2006, Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with Her-2 positive metastatic breast cancer, BMC Cancer, 6, 225, 10.1186/1471-2407-6-225 Orlando, 2017, J. Clin. Oncol., 31, 618 Pai, 2013, Oral metronomic scheduling of anticancer therapy-based treatment compared to existing standard of care in locally advanced oral squamous cell cancers: a matched-pair analysis, Indian J. Cancer, 50, 135, 10.4103/0019-509X.117024 Pandey, 2016, Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: an Indian rural cancer centre experience, South Asian J. Cancer, 5, 59, 10.4103/2278-330X.181627 Pandey, 2016, Outcome of operable oral cavity cancer and impact of maintenance metronomic chemotherapy: a retrospective study from rural India, South Asian J. Cancer, 5, 52, 10.4103/2278-330X.181625 Pasini, 2018, Oral Metronomic Vinorelbine (OMV) in elderly or pretreated patients with advanced non small cell lung cancer: outcome and pharmacokinetics in the real world, Investig. New Drugs, 36, 927, 10.1007/s10637-018-0631-8 Pastina, 2017, Radiotherapy prolongs the survival of advanced non-smallcell lung cancer patients undergone to an immune-modulating treatment with dosefractionedcisplatin and metronomic etoposide and bevacizumab (mPEBev), Oncotarget, 8, 75904, 10.18632/oncotarget.20411 Patil, 2015, Metronomic chemotherapy in platinum-insensitive failures and/or early failures postmultimodality management in oral cancers, Indian J. Med. Paediatr. Oncol., 36, 161, 10.4103/0971-5851.166725 Patil, 2019, Phase I/II study of palliative triple metronomic chemotherapy in platinum refractory oral cancer, J. Clin. Oncol., 37, 3032, 10.1200/JCO.19.01076 Peereboom, 2019, Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells, JCI Insight, 4, 1, 10.1172/jci.insight.130748 Perry, 2010, Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study, J. Clin. Oncol., 28, 2051, 10.1200/JCO.2009.26.5520 Petrioli, 2015, Cisplatin, etoposide, and bevacizumab regimen followed by oral etoposide and bevacizumab maintenance treatment in patients with extensive stagesmall cell lung cancer: a single-institution experience, Clin. Lung Cancer., 16, e229, 10.1016/j.cllc.2015.05.005 Pfeiffer, 1997, Five-day oral etoposide treatment for advanced small-cell lung cancer: Randomized comparison with intravenous chemotherapy, J. Natl. Cancer Inst., 89, 1892, 10.1093/jnci/89.24.1892 Pujol, 2019, An individual patient data meta-analysis of metronomic oral Vinorelbine in metastatic non small cell lung cancer, PLOS ONE., 14, e0220988, 10.1371/journal.pone.0220988 Reardon, 2009, Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a Phase II Study, Br. J. Cancer, 101, 1986, 10.1038/sj.bjc.6605412 Reardon, 2011, Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy, J. Neurooncol., 103, 371, 10.1007/s11060-010-0403-6 Revannasiddaiah, 2015, The results with the addition of metronomic cyclophosphamide to palliative radiotherapy for the treatment of non-small cell lung carcinoma, Ann. Transl. Med., 3, 1 Robles, 2003, Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer, Oncol. Rep., 10, 885 Rochlitz, 2016, BMC Cancer., 16, 780, 10.1186/s12885-016-2823-y Romiti, 2015, Continuous, low-dose capecitabine for patients with recurrent colorectal cancer, Med. Oncol., 32, 54, 10.1007/s12032-015-0496-z Romiti, 2017, Current achievements and future perspectives of metronomic chemotherapy, Investig. New Drugs, 35, 359, 10.1007/s10637-016-0408-x Salem, 2008, Phase II trial of metronomic chemotherapy as salvage therapy for patients with metastatic breast cancer, J. Egypt Natl. Cancer Inst., 20, 134 Samaritani, 2007, Cyclophosphamide “metronomic” chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer, BMC Cancer, 7, 54, 10.1186/1471-2407-7-65 Sanchez-Munoz, 2010, Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer, Oncology, 79, 98, 10.1159/000320602 Schwartzberg, 2014, Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer, Clin. Breast Cancer, 14, 13, 10.1016/j.clbc.2013.09.003 Sharma, 2019, Oral metronomic chemotherapy for recurrent and refractory epithelial ovarian cancer: a retrospective analysis, Indian J. Med. Res., 150, 575, 10.4103/ijmr.IJMR_2030_18 Shawky, 2014, Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – a single-arm phase II study, J. Egypt Natl. Cancer Inst., 26, 195, 10.1016/j.jnci.2014.10.002 Shi, 2014, Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on colon cancer, Cancer Lett., 349, 128, 10.1016/j.canlet.2014.04.002 Shi, 2020, A study of capecitabine metronomic chemotherapy is non-inferior to conventional chemotherapy as maintenance strategy in responders after induction therapy in metastatic colorectal cancer, Trials, 21, 249, 10.1186/s13063-020-4194-6 Shitara, 2018, Regulatory T cells: a potential target in cancer immunotherapy, Ann. N. Y. Acad. Sci., 1417, 104, 10.1111/nyas.13625 Simeone, 2009, “Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma,” ASCO Annual Meeting Proceedings, J. Clin. Oncol., 27 Simkens, 2015, Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the dutch colorectal cancer group, Lancet, 385, 1843, 10.1016/S0140-6736(14)62004-3 Stockhammer, 2010, Continuous low dose temozolomide and celecoxib in recurrent glioblastoma, J. Neurooncol., 100, 407, 10.1007/s11060-010-0192-y Stockler, 2011, Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer, J. Clin. Oncol., 29, 4498, 10.1200/JCO.2010.33.9101 Surmont, 2009, Oral UFT, etoposide and leucovorin in recurrent non-small cell lung cancer: a nonrandomized phase II study, Lung Cancer, 66, 333, 10.1016/j.lungcan.2009.02.016 Tan, 2015, Metronomic vinorelbine (oral) in combination with sorafenib in advanced non-small cell lung cancer, Lung Cancer, 88, 289, 10.1016/j.lungcan.2015.04.001 Tanaka, 2009, Dual therapeutic efficacy of vinblastine as a unique chemotherapeutic agent capable of inducing dendritic cell maturation, Cancer Res., 69, 6987, 10.1158/0008-5472.CAN-09-1106 Tralongo, 2016, Chemotherapy in frail elderly patients with hormone-refractory prostate cancer: a “real world” experience, Prostate Int., 4, 15, 10.1016/j.prnil.2015.12.003 Tupikowski, 2015, Interferon alpha and metronomic cyclophosphamide for metastatic kidney cancer: a phase 2 study, J. Interferon Cytokine Res., 35, 367, 10.1089/jir.2014.0106 Ugurel, 2001, Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival, J. Clin. Oncol., 19, 577, 10.1200/JCO.2001.19.2.577 Van Cutsem, 2000, Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study, J. Clin. Oncol., 18, 1337, 10.1200/JCO.2000.18.6.1337 Van Dodewaard-de Jong, 2015, New treatment options for patients with metastatic prostate cancer: what is the optimal sequence?, Clin. Genitourinary Cancer, 13, 271, 10.1016/j.clgc.2015.01.008 Vincent, 2010, 5FU selectively kills tumor associated myeloid derived suppressor cells resulting in enhanced T cell dependent antitumor immunity, Cancer Res., 69, 3052, 10.1158/0008-5472.CAN-09-3690 Walter, 2012, Pioglitazone, etoricoxib, interferon-a, andmetronomiccapecitabine for metastatic renal cell carcinoma: final results of a prospective phase II trial, Med. Oncol., 29, 799, 10.1007/s12032-011-9982-0 Wang, 2012, An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline and taxane-pretreated metastatic breast cancer: a phase II study, Cancer Chemother. Pharmacol., 69, 515, 10.1007/s00280-011-1728-3 Wang, 2020, Active and effective measures for the care of patients with cancer during the COVID-19 spread in China, JAMA Oncol. Watanabe, 2009, Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, fluorouracil as postoperative chemotherapy in patients with node-negative, high-risk breast cancer: National Surgical Adjuvant Study for Breast Cancer 01 Trial, J. Clin. Oncol., 27, 1368, 10.1200/JCO.2008.18.3939 Welzel, 2015, Metronomic chemotherapy with daily low-dose temozolomide and celecoxib in elderly patients with newly diagnosed glioblastoma multiforme: a retrospective analysis, J. Neurooncol., 124, 265, 10.1007/s11060-015-1834-x Wong, 2017, Continuous oral cyclophosphamide as salvage or maineinance therapy in ovarian, primary peritoneal, and fallopian tube cancers: a retrospective single institute experience, Taiwan. J. Obstret. Gynecol., 56, 302, 10.1016/j.tjog.2017.04.006 Yashi, 2014, Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration resistant prostate cancer: a prospective analysis of consecutive cases, Clin. Genitourinary Cancer, 12, e197, 10.1016/j.clgc.2014.02.007 Yoshimoto, 2012, Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer, Cancer Chemother. Pharmacol., 70, 331, 10.1007/s00280-012-1826-x You, 2020, The official French guidelines to protect patients with cancer against SARS-CoV-2 infection, Lancet Oncol., 10.1016/S1470-2045(20)30204-7 Zustovich, 2013, Sorafenib plus daily low-dose temozolomide for relapsed glioblastoma: a phase II study, Anticancer Res., 33, 3487