A retrospective review of molecular-guided therapy and metronomic therapy on the outcomes of childhood cancers

Christina Roffidal, The University of Texas School of Public Health


Background: Childhood cancer represents only 1% of all new cancers in the United States, yet it remains the leading cause of disease-related death among children 5-15 years of age. Pediatric malignancies and other related conditions have been studied primarily with standardized treatment Phase I, II, III protocols with the expectation of cure. For cancers that respond to the initial therapeutic regimen, this approach has been successful. For many solid tumors this approach has failed. The field of oncology has now been rapidly advancing, towards the use of a molecular diagnostic therapeutic approach also known as personalized cancer care or precision medicine. The target of this molecular approach is the micro-environment rather than the cancer cell, and as such the combination of molecularly-based biological agents and maximum tolerated chemotherapy leads to increased toxicities. Metronomic strategy suggests that the use of chemotherapy at low, continuous doses not only avoids toxic side effects, but also preferentially targets the host biological responses. ^ This retrospective review reported below provides observations to demonstrate the concept that when molecular-guided agents are combined with a metronomic dosing strategy, patients will have milder toxicities (as measured by number of admissions) while maintaining similar outcomes. A descriptive analysis of patients who have been previously treated with the molecularly guided therapies was performed.^ Methods: The study group consisted of a cohort of patients in whom therapy had been designed using a specific biological algorithm based on molecular studies of the tissues. A spectrum of childhood malignancies for which no standard therapies existed was used. Patients previously treated with molecular-guided therapies were identified from a dataset of patients treated at the Pediatric Hematology Oncology department at Tufts Medical Center. This dataset was reviewed and further categorized into dosing strategies of standard maximum tolerated dosing and metronomic dosing. Data involving frequency of hospital admissions and total number of days hospitalized was reviewed, in addition to standard measures such as event free survival, progression free survival and overall survival.^ Results: Twenty-four patients (58% female; 42% male) were identified as having received molecularly-guided therapy. Ages ranged from 0.5months to 26 years old, with the majority of the patients (25%) between the ages of 9-12 years at first line of molecular therapy. The distribution of cancer types varied from Cancer Related Disorders-RALD (4%), LCH (4%), Renal Ca (4%), Thyroid Ca (4%), Soft Tissue Sarcoma (13%), ALL/AML (17%), and CNS (54%). A review of 77 treatment regimens were analyzed and organized into the following therapeutic subgroups: i) Histological/Standard MTD ii) Molecularly Guided/Standard MTD, and iii) Molecularly Guided/Metronomic. The most noteworthy finding reported was that the Molecularly Guided/ Metronomic approach had 87% less number of days of hospitalized on average per regimen than with the Histological/Standard MTD approach, and 77% less than with the Molecularly Guided/ Standard MTD approach.^ Conclusion: Metronomic dosing strategy appears to provide the most promising approach to the future management of childhood cancers, particularly those using molecularly guided therapies.^

Subject Area

Canadian history|Oncology

Recommended Citation

Roffidal, Christina, "A retrospective review of molecular-guided therapy and metronomic therapy on the outcomes of childhood cancers" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10182185.