Maria El Kababri1,2, Sarra Benmiloud3, Siham Cherkaoui4, Jamila El Houdzi5, Khadija Maani6, Nawal Ansari1, Nissrine Khoubila4, Amina Kili1, Mohammed El Khorassani1, Abdellah Madani4, Mohammed Adnane Tazi7, Samir Ahid8,9, Laila Hessissen1,2, Asmaa Quessar4, Mhamed Harif4, Mohammed Khattab1, Nicolas André10,11,12. 1. Paediatric Haematology and Oncology Center, Children's Hospital of Rabat, Mohammed V University, Rabat, Morocco. 2. Metronomics Global Health Initiative, Rabat, Morocco. 3. Paediatric Haematology and Oncology Unit, Hospital Hassan II, Fes, Morocco. 4. Paediatric Haematology and Oncology Service, Hospital 20 Aout, Casablanca, Morocco. 5. Pediatic Haematology and Oncology Unit, Hospital Mohamed VI, Marrakech, Morocco. 6. Paediatric Haematology and Oncology Unit, Hospital Ibn Rochd, Casablanca, Morocco. 7. National School of Public Health, Rabat, Morocco. 8. Pharmacoeconomics and Pharmacoepidemiology Research Team, Mohammed V University, Rabat, Morocco. 9. Laboratory of Biostatistics, Clinical and Epidemiological Research, Mohammed V University, Rabat, Morocco. 10. Paediatric Haematology and Oncology Department, La Timone Children's Hospital, Assistance Publique Hopitaux de Marseille, Marseille, France. 11. SMARTc Unit, Centre de Recherche en Cancérologie de Marseille, Inserm U1068, Aix Marseille Univ, Marseille, France. 12. Metronomics Global Health Initiative, Marseille, France.
Abstract
BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.
BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.