Adjuvant chemotherapy in osteosarcoma ― effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin: preliminary results of the COSS 80 study

• Published in: Journal of cancer research and clinical oncology 1983, Vol.106 (S1), p.1-7
• Main Authors: WINKLER, K, BERON, G, HAVERS, W, HENZE, G, HINDERFELD, L, HOCKER, P, JOBKE, A, JURGENS, H, KABISCH, H, LANDBECK, G, PREUSSER, P, PRINDULL, G, KOTZ, R, RAMACH, W, RITTER, J, SEKERA, J, TREUNER, J, WUST, G, SALZER-KUNTSCHIK, M, BECK, J, BECK, W, BRINDEIS, W, EBELL, W, ERTTMANN, R, GOBEL, U
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Bone Neoplasms - drug therapy; Bone Neoplasms - surgery; Chemotherapy; Cisplatin - administration & dosage; Clinical Trials as Topic; Dactinomycin - administration & dosage; Doxorubicin - administration & dosage; Drug Therapy, Combination; Humans; Interferons - therapeutic use; Medical sciences; Methotrexate - administration & dosage; Osteosarcoma - drug therapy; Osteosarcoma - surgery; Pharmacology. Drug treatments; Preoperative Care; Random Allocation
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/BF00625042

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.