Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of
adjuvant chemotherapy after aggressive local treatment of high-grade
sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal
sarcomas). All patients had complete resection of gross
tumor and underwent postoperative
radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received
adjuvant chemotherapy consisting of
doxorubicin (less than or equal to 550 mg/m2),
cyclophosphamide (less than or equal to 5500 mg/m2), and
methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the
chemotherapy arm was 77%, compared to 49% in the no-
chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with
tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the
chemotherapy arm was 92%, compared to 47% in the no-
chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the
chemotherapy arm was 82%, compared to 61% in the no-
chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of
contraindications to
chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received
chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with
chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with
sarcomas of the trunk (39 patients) demonstrated the greatest benefit from
chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with
chemotherapy was
doxorubicin-induced
cardiomyopathy, which resulted in clinically apparent
congestive heart failure in five patients. Thus, the use of
chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.