Author(s): C. R. Macedo,
A. M. Cappellano, D. T. Noguchi, A. P. Martinho, C. G. Dias, C. G.
Dias, R. C. Malheiros, A. H. Dutra, M. Grings, A. L. Pires, A. S.
Petrilli; Instituto de Oncologia Pediátrica, São Paulo, Brazil
describe the experience with outpatient administration of high dose
methotrexate (HDMTX) and leucovorin rescue for osteosarcoma treatment
at Instituto de Oncologia Pediátrica.
Methods: HDMTX (12g/m²)
is administered as part of the Brazilian Osteosarcoma Treatment Group
Protocol in an ambulatory basis. Daily MTX serum levels and fluid
controls follows until the serum level is <0,2 µ/L. Families were
oriented to measure urinary pH and volume, PO intake and to adjust
leucovorin dose as needed. To achieve treatment adherence, a family
education program was developed. Concomitantly to HD chemotherapy, low
dose oral cyclophosphamide and MTX (metronomic treatment) were provided
to metastatic (M) patients. This is a retrospective analysis of the
HDMTX courses administered between 2006 and 2008.
of 341 HDMTX infusions, administered to 42 patients, 42.5% had abnormal
serum levels at hour 24, 8.8% at hour 48 and 33.2% at hour 72. After
required interventions, 2.9% (n = 8) had serum levels >0.2 µ/L at
hour 72 leading to delayed excretion. Of these, 7 had also creatinine
elevation and main adverse events were mucositis, reversible
transaminasis elevation and one sepsis. In the overall analysis, other
toxicities included mucositis grade II (20%), nefrotoxicity (5.6%) and
neutropenia grades III and IV (25.4%). Serious adverse events of
seizure, allergic reaction, and Steven Johnson's Syndrome lead to
suspension of future HDMTX administration in 4 patients (01
metastatic). The main differences found between M and non-M patients
were 16.8% versus 8.7% of leucopenia grade IV and 12.1% versus 6.6% of
anemia grades III and IV.
Conclusions: Similar to other
authors' experience, outpatient administration of HDMTX lead to
elevated serum levels in 42.5% of the infusions, demonstrating the
importance of a well trained staff and early introduction of supportive
therapies to avoid associated toxicities. To a developing country, this
approach helps lowering treatment costs and infection risks and
increases patient adherence to treatment, with acceptable toxicities,
even with the introduction of metronomic treatment.
Outpatient administration of high-dose methotrexate for osteosarcoma treatment in Brazil.
Author(s): C. R. Macedo,