Repetto L, Balducci L. A case for geriatric oncology. Lancet Oncol. 2002;3:289–97.

Article  PubMed  Google Scholar 

Scotté F, Bossi P, Carola E, Cudennec T, Dielenseger P, Gomes F, et al. Addressing the quality of life needs of older patients with cancer: A SIOG consensus paper and practical guide. Ann Oncol. 2018;29:1718–26.

Article  PubMed  Google Scholar 

Kumar Pal S, Katheria V, Hurria A. Evaluating the Older Patient with Cancer: Understanding Frailty and the Geriatric Assessment. CA Cancer J Clin. 2010;60:120–32.

Article  Google Scholar 

Bellelli F, Consorti E, Hettiarachchige TMK, Rossi P, Lucchi T, Froldi M, et al. Relationship among age, education and frailty in older persons. J Frailty Aging. 2023;12:326–8.

CAS  PubMed  Google Scholar 

Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. The Lancet. 2013;381:752–62.

Article  Google Scholar 

Kareva I, Waxman DJ, Klement GL. Metronomic chemotherapy: An attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance. Cancer Lett. 2015;358:100–6.

Article  CAS  PubMed  Google Scholar 

Tralongo AC, Fratamico RS, Russo C, Sbrana A, Antonuzzo A, Danova M. Anti-cancer treatment strategies in the older population: Time to test more? Geriatrics. 2021;6:42. This article highlights the limitations and critical issues of antineoplastic therapies traditionally used to treat elderly cancer patients (including MTD), emphasizing the advantages of using MCT and encouraging its use to improve the management of the geriatric cancer population.

Article  PubMed  PubMed Central  Google Scholar 

Bocci G, Kerbel RS. Pharmacokinetics of metronomic chemotherapy: A neglected but crucial aspect. Nat Rev Clin Oncol. 2016;13:659–73. This article highlighted the main features of MCT, describing its pharmacokinetic and pharmacodynamic profiles that have emerged from various preclinical and clinical studies.

Article  CAS  PubMed  Google Scholar 

Kim J, Kim YM. Tumor endothelial cells as a potential target of metronomic chemotherapy. Arch Pharm Res. 2019;42:1–13.

Article  PubMed  Google Scholar 

Wildiers H. Mastering chemotherapy dose reduction in elderly cancer patients. Eur J Cancer. 2007;43:2235–41.

Article  CAS  PubMed  Google Scholar 

Bocci G, Nicolaou KC, Kerbel RS. Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res. 2002;62:6938–43.

CAS  PubMed  Google Scholar 

Bocci G, Francia G, Man S, Lawler J, Kerbel RS. Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci U S A. 2003;100:12917–22.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Browder T, Butterfield CE, Kräling BM, Shi B, Marshall B, O’Reilly MS, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 2000;60:1878–86.

CAS  PubMed  Google Scholar 

Panthi VK, Dua K, Singh SK, Gupta G, Hansbro PM, Paudel KR. Nanoformulations-based metronomic chemotherapy: mechanism, challenges, recent advances, and future perspectives. Pharmaceutics. 2023;15:1192.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Natale G, Bocci G. Does metronomic chemotherapy induce tumor angiogenic dormancy? A review of available preclinical and clinical data. Cancer Lett. 2018;432:28–37.

Article  CAS  PubMed  Google Scholar 

Orecchioni S, Talarico G, Labanca V, Calleri A, Mancuso P, Bertolini F. Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma. Br J Cancer. 2018;118:1329–36.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maiti R. Metronomic chemotherapy. J Pharmacol Pharmacother. 2014;5:186–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Muthusamy P, Chary KV, Nalini GK. Metronomic chemotherapy: Seems prowess to battle against cancer in current scenario. J Clin Diagn Res. 2016;10:FC09-FC13.

Bocci G, Tuccori M, Emmenegger U, Liguori V, Falcone A, Kerbel RS, et al. Cyclophosphamide-methotrexate “metronomic” chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation. Annal Oncol. 2005;16:1243–52.

Article  CAS  Google Scholar 

Cazzaniga ME, Munzone E, Bocci G, Afonso N, Gomez P, Langkjer S, et al. Pan-European expert meeting on the use of metronomic chemotherapy in advanced breast cancer patients: The Penelope project. Adv Ther. 2019;36:381–406.

Article  PubMed  Google Scholar 

Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013;16:481–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Banchi M, Lanzolla T, Di Napoli A, Bandini A, Bocci G, Cox MC. Complete remission of a diffuse large B-cell lymphoma in a young patient, with severe tuberous sclerosis, treated with metronomic chemotherapy and ibrutinib: a case report. Chemotherapy. 2023:1–5.

Riesco-Martinez M, Parra K, Saluja R, Francia G, Emmenegger U. Resistance to metronomic chemotherapy and ways to overcome it. Cancer Lett. 2017;400:311–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sureshkumar K, Srinivasan K, Lingeshwaran GP, Durairaj M, Thiruvengadam G, Mary Martin Daniel PJ, et al. Toxicity profile, adverse drug reactions and drug-drug interactions among geriatric cancer patients under metronomic chemotherapy in a South Indian tertiary care hospital. J Oncol Pharm Pract. 2023;29:778–84. This study examined the toxicity profile and drug-drug interactions in elderly geriatric cancer patients receiving MCT.

Article  CAS  PubMed  Google Scholar 

Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, et al. Global increase in breast cancer incidence: risk factors and preventive measures. Biomed Res Int. 2022;2022:9605439.

Article  PubMed  PubMed Central  Google Scholar 

DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69:438–51.

Article  PubMed  Google Scholar 

Di Desidero T, Xu P, Man S, Bocci G, Kerbel RS. Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer. Oncotarget. 2015;6:42396–410.

Article  PubMed  PubMed Central  Google Scholar 

De Iuliis F, Salerno G, Taglieri L, Lanza R, Scarpa S. On and off metronomic oral vinorelbine in elderly women with advanced breast cancer. Tumori. 2015;101:30–5.

Article  PubMed  Google Scholar 

Wildiers H, Tryfonidis K, Dal Lago L, Vuylsteke P, Curigliano G, Waters S, et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018;19:323–36. This multicenter, open-label, randomized, phase 2 study in 30 centers in eight European countries compared the efficacy of anti-HER2 treatment with or without MCT in elderly patients with HER2-positive metastatic breast cancer.

Article  CAS  PubMed  Google Scholar 

Krajnak S, Decker T, Schollenberger L, Rosé C, Ruckes C, Fehm T, et al. Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046. J Cancer Res Clin Oncol. 2021;147:3391–400.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Addeo R, Sgambato A, Cennamo G, Montella L, Faiola V, Abbruzzese A, et al. Low-dose metronomic oral administration of vinorelbine in the first-line treatment of elderly patients with metastatic breast cancer. Clin Breast Cancer. 2010;10:301–6.

Article  CAS  PubMed  Google Scholar 

Cazzaniga ME, Torri V, Riva F, Porcu L, Cicchiello F, Capici S, et al. Efficacy and safety of vinorelbine-capecitabine oral metronomic combination in elderly metastatic breast cancer patients: VICTOR-1 study. Tumori. 2017;103:e4–8.

Article  CAS  PubMed  Google Scholar 

Bottini A, Generali D, Brizzi MP, Fox SB, Bersiga A, Bonardi S, et al. Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients. J Clin Oncol. 2006;24:3623–8.

Article  CAS  PubMed  Google Scholar 

Crivellari D, Gray KP, Dellapasqua S, Puglisi F, Ribi K, Price KN, et al. Adjuvant pegylated liposomal doxorubicin for older women with endocrine nonresponsive breast cancer who are NOT suitable for a “standard chemotherapy regimen” : The CASA randomized trial. Breast. 2013;22:130–7.

Article  PubMed  Google Scholar 

Fontana A, Falcone A, Derosa L, Di Desidero T, Danesi R, Bocci G. Metronomic chemotherapy for metastatic prostate cancer: A “young”concept for old patients? Drugs Aging. 2010;27:689–96.

Article  CAS  PubMed  Google Scholar 

Parshad S, Sidhu AK, Khan N, Naoum A, Emmenegger U. Metronomic chemotherapy for advanced prostate cancer: A literature review. J Clin Med. 2022;11:2783.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simsek C, Esin E, Yalcin S. Metronomic chemotherapy: A systematic review of the literature and clinical experience. J Oncol. 2019;2019:5483791.

Article  PubMed  PubMed Central  Google Scholar 

Petrylak DP, Tangen CM, Hussain MHA, Lara PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. New Engl J Med. 2004;351:1513–2