Adjuvant adriamycin and cis-diamminedichloroplatinum (cis-platinum) in primary osteosarcoma

Abstract

Twelve consecutive patients with osteosarcoma who were without evidence of metastases were treated with Adriamycin and cis-platinum in an adjuvant fashion. The primary lesion was in the distal femur in five patients, proximal tibia in three, and one each in the proximal femur, proximal humerus, sacrum, and a previously irradiated orbit. Surgery consisted of amputation in eight, limb-salvage procedures in two, and regional resections in the patients with orbital and sacral lesions. Postoperatively, Adriamycin at 30 mg/m2/d, for three days alternated every three weeks with cis-platinum, 100 mg/m2, once daily or 60 mg/m2/d, for two days i.v. drip forced i.v. fluid diuresis. Adriamycin was given to a total dose of 540 mg/m2. Ten of 12 patients remain continually disease-free with a median time on study of 23+ months (range 12+-41+ months). Local recurrences, without evidence of metastatic disease, occurred in the patient with the orbital lesion and the patient who underwent the regional resection for the lesion of the proximal humerus at 20 and 17 months from diagnosis, respectively. Nine patients are off all chemotherapy from 6+ to 33+ months (median 22+ months). Administration of cis-platinum was limited to eight courses because of renal and ototoxicity. Despite appreciable toxicity, this chemotherapeutic regimen appears to be a highly effective adjuvant in the management of primary nonmetastatic osteosarcoma.

Cisplatin dose rate as a risk factor for nephrotoxicity in children

“…The results of this follow-up study confirm previous reports of the frequency, nature and severity of cisplatin-induced glomerular and proximal nephron nephrotoxicity in children, leading to clinically important reductions in GFR and serum magnesium concentration (Ettinger et al, 1981;Hayes et al, 1981;Womer et al, 1985;Goren et al, 1986;Sheldon et al, 1987;Bianchetti et al, 1990;Brock et al, 1991). These adverse effects occurred despite the use of hyperhydration protocols, which appear to reduce the frequency and severity of nephrotoxicity, rather than abolish it altogether (Daugaard and Abildgaard, 1989).…”

Canine Osteosarcoma

“…Reviews of the actions, indications, and toxicities of these drugs in the dog are Studies in humans have demonstrated a more favorable response of patients with osteosarcoma to doxorubicin and cisplatin than to other drugs. 15 treatment of advanced, unresectable, or metastatic osteosarcoma disclosed more responses in patients treated with combination doxorubicin/cisplatin than those treated with cisplatin alone. 16 The 19 dogs treated with amputation alone had longer survival times than the dogs of the classic study by Brodey.6 However, none of these dogs survived longer than 16 months, whereas 3% of the historic control dogs lived 2 years or longer.6 It is difficult to comment on metastatic patterns, as only nine of these 19 dogs had radiographs taken after surgery.…”

Radiation-induced malignant fibrous histiocytoma of the maxilla

“…The effectiveness of chemotherapy is also controversial and has yet to demonstrate definitive benefit [28]. Ettinger et al [30] reported excellent results using postoperative cisplatin and doxorubicin in patients with nonmetastatic osteosarcoma. A recent study by Hugate et al [31] reported that neoadjuvant chemotherapy (intraarterial cisplatin and intravenous doxorubicin) improved survival rates of primary high-grade extremity osteosarcoma and MFH of the bone.…”