Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

Abstract

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Selected current data on metronomic therapy (and its promise) from India

“…indicate that there could be potential benefit from maintenance therapy, especially if it can contribute to achieving an OS of 69% at 5.7 years. [ 10 11 ]…”

Management of isolated recurrence of extramedullary myeloid tumor at a single site

“…This approach has helped decrease the overall relapse rate. [14] To conclude, our case report illustrates that relapse of acute myeloid leukemia can occur at unusual sites and can often pose a therapeutic dilemma. There is need for a consensus doctrine for the management of isolated EMR and a clarification of the role of transplant in this setting.…”

Metronomic therapy in pediatric oncology: A snapshot

“…Ali and El‐Sayed published the clinical experience of metronomic combinations in relapsed pediatric malignancies in Egyptian children . Potential use of metronomic therapy in pediatric acute myeloid leukemia and Ewing sarcoma, along with rural outreach programs based on metronomics, have also been developed in India . The clinical experiences from low‐ and middle‐income countries with affordable regimens with encouraging results will likely allow more patients to be treated more cost effectively in economies where new drugs may not be accessible.…”

“…Further adding to this, are the empiricism of metronomic protocols, inconsistencies in reporting, various terminologies and vague definitions, lack of risk‐related comparator groups, absence of reliable biomarkers, and lack of large randomized Phase III trials. Lack of support from the pharmaceutical industry and the reluctance to term some of the successful RCTs as metronomic, for example CAIRO3, S1 in adjuvant therapy of gastric cancer, are other practical reasons fuelling this skepticism.…”