Metronomics Global Health Initiative

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Update about the Moroccan Society of Pediatric Hematology/Oncology Phase II metronomic trial.

Cure rates in pediatric cancer can reach 80% in high income countries (HIC). However, 80% children are living low income countries where cure rates often don’t exceed 35%. Children with metastatic, unresectable, or recurrent cancer continue to have poor prognosis and the treatment of these patients with second-line intensive or experimental treatments with new expensive drugs, as it is done in HIC nonrealistic option in most of the African countries.

In Morocco, we have previously reported cases of disease stabilization and/or second complete remission in children with recurrent or relapsed malignant disease (SIOP Africa Ghana 2005) under prolonged low dose of cyclophosphamide treatment. Besides, a study from Mali, another LMIC African country, reported the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. These findings led pediatricien from Morroco to look closely at the concept of metronomic chemotherapy (MC) for children with cancer treated in Morocco.

Pr Laila Hessissen and Pr Maria El Kababri with the help of MGHI therefore initiated in 2014 a prospective multicentre metronomic phase II trial with a cyclophosphamide, etoposide, and valproic acid combination in children with either a relapsing/refractory tumors or a very advanced disease. This project is conducted by The Moroccan Society of Pediatric Hematology/Oncology with the financial support of the Lalla Salma Foundation Prevention and Treatment of Cancer.

Intravenous Etoposide is used by oral route because oral form is not available in Morocco. The primary objective of the protocol is to evaluate the anti-tumor effect defined by:
- Progression free survival (PFS) after 4 months (4 cycles), 8 and 12 months of treatment.
- Response rate after 4 months, 8 and 12 months of treatment. The secondary objectives are:
- Evaluate the tolerance of treatment
- Evaluate the quality of life (at D0 and every 4 months)
- Evaluate the analgesic consumption and the transfusion requirements

The study is ongoing and 20 patients from 3 out of the 4 Moroccan pediatric oncology centers have been included so far. Tolerance of treatment and compliance are excellent.

Treated patients:
- Ewing : 4 patients
- Osteosarcoma : 3
- Neuroblastome : 2
- Rhabdomyosarcoma : 4
- MGT : 2
- Nephroblastoma : 2
- UCNT : 1
- Medulloblastoma : 1
- STS : 1