Chimioterapia metronomică în cancerul mamar triplu negativ operabil

Triple negative breast cancer (TNBC) has a poor prognosis even in early stages, denoting a 5-year relapse rate of 30% in stage I to III of disease, with less than one third of patients being alive at 5 years after relapse event. There is no validated maintenance adjuvant treatment in hormone negative, HER2-negative breast cancer phenotype. Metronomic chemotherapy (MT), chronic administration of cytotoxic agents in low doses, confers the advantage of reduced toxicities and of an antiangiogenic and immunomodulatory complementary effect. Running a general review on the benefit of adjuvant MT in operable TNBC population, capecitabine, cyclophosphamide, methotrexate and vinorelbine, either in monotherapy or in combination, were found most studied. Generally, this schedule was well tolerated even in one-year administration regimen. In two Egyptian phases II studies exploring the safety of capecitabine, the administration for six months, respectively one year, lead to an estimated median disease free survival (DFS) of 42.4 months (95% CI [39.02-45.79]) respectively 41.7 months (95% CI [36.5-46.9]). However,  phase III studies reported grade III-IV adverse events in near a quarter of patients for 8 cycles of capecitabine standard dose after adjuvant therapy and no survival benefit of one-year cyclophosphamide-methotrexate metronomic compared to standard approach. Several ongoing phase III studies evaluate cyclophosphamide efficacy for six months to one year, following standard treatment. Metronomic adjuvant maintenance treatment seems feasible in terms of toxicity in operable TNBC. Survival benefit remains to be proven.