Toxicity monitoring and recommendations for changes to
chemotherapy
During chemotherapy, complete blood cell counts and blood chemistry were
obtained at the baseline, weekly, and before each cycle. Toxicity was
graded using the National Cancer Institute’s Common Toxicity Criteria
(CTC), version 5.0. In the event of significant diarrhea (≥ CTC grade
III), the dose of irinotecan had to be reduced by 25% for the
subsequent course. If there were further episodes, the dose had to be
further reduced or even omitted.
Drug doses for younger patients had to be calculated by body surface
area, then reduced by 50% or 33% for children under 6 or 12 months
old, respectively.
As a general criterion for evaluating the feasibility of this new
regimen, we established that more than 70% of cycles would have to be
administered with a delay of less than one week. We also compared the
overall duration of the treatment with a historical series of patients
with metastatic RMS treated in Italy from November 2013 to January 2020
and included in the EpSSG MTS-2008 protocol. These patients received 9
cycles of chemotherapy at 3-week intervals: 4 cycles of the IVADo
regimen (ifosfamide, vincristine, actinomycin D, and doxorubicin)
followed by 5 cycles of IVA (ifosfamide, vincristine, actinomycin D)
(9). These patients subsequently received maintenance therapy with
cyclophosphamide and vinorelbine, but this part of the treatment was not
considered for the purposes of our comparison.
RESULTS
Between November 2013 to January 2020, this study enrolled 23 patients
aged from 1.3 to 25 years
(median 10.9 years), and 15 were male. The study population included 11
newly-diagnosed metastatic sarcomas (10 RMS and 1 DSRCT) and 12 relapsed
tumors (7 RMS, 4 ES, and 1 DSRCT). All patients with metastatic disease
had important metastatic diffusion. The patients with DSRCT had
peritoneal dissemination (Table 1).
All newly-diagnosed patients received the IrIVA combination, while in
the group of relapsed patients, 2 received IrIVA and 10 IrVAC.