Preoperative chemotherapy, both with or without concurrent radiotherapy, is feasible among patients with localized, high-risk soft-tissue sarcoma, according to a new phase III trial.
Preoperative chemotherapy, both with or without concurrent radiotherapy (RT), is feasible among patients with localized, high-risk soft-tissue sarcoma, according to a new phase III trial.
The trial, conducted by the Italian Sarcoma Group and the Spanish Sarcoma group, previously found that 3 cycles of adjuvant chemotherapy are not inferior to 5 cycles with regard to overall survival and relapse-free survival. The new report, led by Alessandro Gronchi, MD, of the Istituto Nazionale dei Tumori in Milan, Italy, focused on the toxicity of the preoperative chemotherapy and the feasibility of combining it with RT in selected patients.
The study included 321 patients randomized to either 3 preoperative cycles of epirubicin plus ifosfamide or those 3 cycles plus 2 postoperative cycles; 303 of those patients were included in this analysis. A total of 152 patients received concurrent RT preoperatively, at a total dose of 44 to 50 Gy, and 126 patients received postoperative RT.
Grade 4 leucopenia occurred in 61.4% of all patients in the trial. Grade 3/4 anemia occurred in 22.4% of patients, and grade 3/4 thrombocytopenia occurred in 23.8%. There were no fatal toxicities.
Among only those patients who underwent concurrent preoperative RT, 66.4% experienced grade 4 leucopenia, 24.3% experienced grade 3/4 anemia, and 31.6% experienced grade 3/4 thrombocytopenia. In the patients who received preoperative chemotherapy alone, these rates were 56.3%, 20.5%, and 15.9%, respectively.
The rates of those complications were slightly higher in a subgroup of patients aged 65 years and older, at 71.8%, 23.1%, and 38.5%, respectively. Wound complications were seen in 17.1% of patients who received preoperative RT, and in 9.9% of those receiving chemotherapy alone; wound complications occurred in 17.9% of the elderly patients subgroup.
The mean overall chemotherapeutic dose intensity was 94.9%, and the average relative dose intensity was 93.9% in preoperative RT patients and 95.5% in chemotherapy alone patients; it was 92.6% in elderly patients.
Logistic regression analysis showed that only gender was significantly associated with grade 4 leucopenia, with female patients 2.5 times as likely to develop the complication. This was also true for grade 3/4 anemia, while both age and preoperative RT were both significantly associated with grade 3/4 thrombocytopenia.
“In conclusion, concomitant chemotherapy/RT can be proposed for patients with soft-tissue sarcoma when surgical reasons suggest that major preoperative shrinkage may help,” the authors wrote.