Outpatient administration of high-dose methotrexate for osteosarcoma treatment in Brazil.

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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
Background: We
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.
Results: Out
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.