Preoperative chemotherapy is feasible for high-risk localized soft-tissue sarcomas of the limbs or superficial trunk, even with concurrent radiotherapy and even in selected elderly patients, investigators reported online Sept. 7 in Journal of Clinical Oncology.
Full-dose preoperative chemotherapy now can be offered and an excellent chemotherapeutic dose intensity now can be achieved with concomitant radiotherapy in cases “when surgical reasons suggest that major preoperative shrinkage may help,” said Dr. Elena Palassini of Istituto Nazionale dei Tumori, Bologna (Italy), and her associates in the Italian Sarcoma Group and Spanish Sarcoma Group.
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The investigators already reported the efficacy results of their international phase III randomized clinical trial assessing preoperative chemotherapy (with or without radiotherapy, at the treating physician’s discretion). In the current analysis, they focused on the toxicity data for 303 of the trial participants, all of whom had high-grade, deep, large, adult-type soft-tissue sarcomas arising from the extremities or trunk wall.
The median patient age was 48 years (range, 15-79 years), and 13% of the study population was aged 65 years or older. A total of 152 received preoperative radiotherapy along with epirubicin plus ifosfamide.
“The most interesting clinical finding was the tolerability of the combination of preoperative chemotherapy and radiotherapy,” which is particularly remarkable because patients chosen for combination treatment had the largest tumors and the most challenging presentations, the investigators wrote.
Participants who received combination preoperative therapy showed “only limited worsening of toxicities” compared with those who had preoperative chemotherapy alone, Dr. Palassini and her associates said (J Clin Oncol. 2015 Sept. 7. doi: 10.1200/JCO.2015.62.9394).
Grade 3 or 4 thrombocytopenia was more frequent with combined therapy than with chemotherapy alone, but grade 4 leukopenia and grade 3 or 4 anemia were not. There were no cases of fatal toxicity, and the rate of wound complications was not significantly higher when radiotherapy was added to chemotherapy (17.1%) than when it was not (9.9%).
Even though some patients failed to complete all planned cycles of chemotherapy or experienced dose reductions or interruptions because of toxic effects, the overall median chemotherapeutic dose index remained “excellent” at greater than 90%. This was true even in patients aged 65 years and older, which “clearly suggests the possibility of selecting and treating at least a proportion of [older] patients in the adjuvant setting with full-dose regimens.” This finding is especially important because older patients comprise 30% of those newly diagnosed as having soft-tissue sarcoma, the investigators noted.
The authors did not identify a sponsor of this study. Dr. Palassini reported having no relevant financial disclosures, and her associates reported ties to numerous industry sources.