Prospective randomized evaluation of the role of limb-sparing surgery, radiation therapy, and adjuvant chemoimmunotherapy in the treatment of adult soft-tissue sarcomas

Between May, 1975, and June, 1977, 49 patients were entered into a prospective randomized evaluation of the role of limb-sparing surgery and adjuvant chemoimmunotherapy in the treatment of adult patients with clinically localized soft-tissue sarcomas. Patients with extremity soft-tissue sarcomas were randomized to receive either amputation at or above the joint proximal to the tumor or to receive a limb-sparing operation that preserved function of the extremity followed by postoperative radiotherapy. All patients with extremity and truncal sarcomas were randomized to receive either adjuvant chemotherapy with escalating doses of Adriamycin and cyclophosphamide plus six cycles of high-dose methotrexate or the same chemotherapy plus immunotherapy with intravenous and subcutaneous Corynebacterium parvum. Treatment groups have been compared directly as well as analyzed with respect to 66 comparable historical control patients treated in the Surgery Branch of the National Cancer Institute with radical surgery but no adjuvant chemotherapy or radiation therapy. Actuarial analysis of our current protocol patients as compared with historical controls reveals an improvement in disease-free interval (P < 0.001) as well as improved survival (P < 0.001). Five recurrences have been seen in the 49 protocol patients. Only one local recurrence has occurred in 16 patients with extremity lesions randomized to receive limb-sparing surgery plus radiation therapy. Preliminary results of this study indicate that adjuvant chemotherapy with Adriamycin, Cytoxan, and methotrexate may be of benefit in preventing disease recurrence in adult patients with soft-tissue sarcomas. Preliminary results indicate that limb-sparing surgery plus radiation therapy may be as effective as radical amputation in achieving local control in this disease.