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.