A total of 48 patients with non-metastatic osteosarcoma of the extremities were treated with a new neoadjuvant chemotherapy protocol which, prior to surgery, included the use of high dose methotrexate, cisplatin, adriamycin and ifosfamide. Cisplatin was administered intra-arterially, whereas the other drugs were given intravenously. In all of the cases response to this chemotherapy protocol was very good, allowing for conservative treatment in 46 out of 48 patients. Histological evaluation of chemotherapy response showed good (> 90%) and total necrosis in 87 and 54% of the cases, respectively. Drug toxicity was acceptable. Results were significantly better than those previously obtained in our and in other institutes when only three drugs were used (methotrexate, cisplatin, and adriamycin) in the preoperative treatment scheme. Since it has been demonstrated that grade of histological response to preoperative chemotherapy, and prognosis are closely related in osteosarcoma of the extremities treated with neoadjuvant chemotherapy, in addition to allowing for the use of conservative surgery in the majority of cases, this new protocol may also lead to a significant increase in the patient cure rate.

Adolescent↗

PubMedDate not supplied

[Non-metastatic osteosarcoma of the extremities: the pattern of relapse as a function of the type of treatment and of the modulation of the radiological follow-up of the thorax].

The authors analysed the patterns of recurrence of osteosarcoma of the extremities treated between 1959 and 1989 either with surgery alone (1959-71) or with combined surgery and adjuvant (1972-82) or neoadjuvant chemotherapy (1983-89). In a total of 452 patients with recurrent osteosarcoma, the initial site of metastasis was the lung in 88% of cases independently of the type of treatment received. The mean period of onset of pulmonary metastasis differed according to the type of treatment performed: 8 months for patients treated with surgery alone; 15.9 months for those treated with adjuvant chemotherapy and 20.3 months for patients treated with neoadjuvant chemotherapy. The incidence of metastases appearing within 12 months of FU was 87%, 56% and 21% respectively. In a most recent and effective neoadjuvant protocol (66% DFS), the incidence of recurrence owing to pulmonary metastasis during the first year of FU was 2% and as much as 75% of all recurrences were concentrated in the following 18 months. Surgery for pulmonary metastasis in patients undergoing chemotherapy was performed in 54 cases with secondary healing in 14 (26%). On the basis of these results the authors suggest a scheme of radiological follow-up for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy with intensified controls (every 2 months) during the period with the highest risk of recurrence (13-20 months) and four-monthly controls during the first year and after 31 months of FU. In order to increase the efficacy of FU controls during the high-risk period, the a. propose using CT controls instead of chest X-rays at months 14, 20 and 26.

Adult↗

PubMedDate not supplied

Neoadjuvant chemotherapy for malignant fibrous histiocytoma of bone and for osteosarcoma of the limbs: a comparison between the results obtained for 21 and 144 patients, respectively, treated during the same period with the same chemotherapy protocol.

Twenty-one patients affected with malignant fibrous histiocytoma localized in the limbs were treated by pre- and postoperative chemotherapy (neoadjuvant). Preoperatively methotrexate (i.v.), cisplatinum (i.a.), and adriamycin (i.v.) were administered. Postoperatively the same drugs (in patients who responded well) or with the addition of ifosfamide and VP 16 (in those who responded poorly) were administered. Twenty resections and 1 amputation followed. The response to chemotherapy was good in 7 patients, and poor in 14. At a mean follow-up of 6.3 years 15 patients were disease-free and 6 had relapses. These results appear to be comparable to those for 144 patients affected with osteosarcoma of the limbs treated at the same time with the same protocol. The percentage of good responses and pulmonary metastases was higher in cases of osteosarcoma. Pre- and postoperative chemotherapy increases the percentage of healing in malignant fibrous histiocytoma. The lower percentage of good responses and the different type of relapse as compared to osteosarcoma indicate that preoperatively chemotherapy different from that used for osteosarcoma should be conducted.

Adult↗

PubMedDate not supplied

[A prospective study on nephrotoxicity induced by continuous infusion of high-dose ifosfamide (15/m2)].

BACKGROUND: A good response rate to high-dose ifosfamide (HDIFO) has been reported in metastatic osteosarcoma and soft tissue tumors. As standard dose of IFO (< 12 g/m2) can give several renal complications and patients previously treated with nephrotoxic drugs are at high risk of nephrotoxicity, a prospective study to evaluate the pattern of nephrotoxicity induced by HDIFO was carried out. METHODS: Twelve patients (11 metastatic osteosarcoma, 1 synovial sarcoma; mean age 17, R 14-34) were treated with 4 courses of HDIFO/ MESNA (15 g/m2, IV 5 day continuous infusion with bicarbonate and K supplements). All but two were previously treated with cisplatin and methotrexate. Several parameters of renal function were measured before treatment, after each HDIFO course and two months after chemotherapy completion. RESULTS: Significant changes in the urinary excretion of beta 1-microglobulin, beta 2-microglobulin, Alanine Aminopeptidase, N-Acetil-beta, D-glucosaminidase and a significant reduction in phosphate tubular absorbtion according to the cumulative dose of IFO infused, were observed. Phosphaturia and hypophosphatemia occurred in all the patients studied. In 5 patients, CrCl fell below 70 ml/min with normal serum creatinine level after 45 g/m2 IFO. Plasma bicarbonate concentration less than 20 mmol/l was observed in 5 of 48 HDIFO courses. Glycosuria was detected in 4 patients. Two months after chemotherapy completion, mild glycosuria and slightly reduced CrCl persisted in two patients, whereas the other parameters of renal function studied were similar to the baseline values. An acute, usually reversible subclinical nephrotoxicity involving glomerule and renal tubule was demonstrated in all the patients treated with HDIFO. A persisting subclinical renal impairment was shown with mild glycosuria (2/12 patients) and slightly reduced CrCl (2/12 patients).

Adolescent↗

PubMedDate not supplied

The effect of intra-arterial versus intravenous cisplatinum in the neoadjuvant treatment of osteosarcoma of the limbs: the experience at the Rizzoli Institute.

The effect of intra-arterial versus intravenous infusion of cisplatinum on the histological response of osteosarcoma of the limbs was evaluated based on the results of three studies in which CDP was preoperatively associated with MTX and ADM (1st study), and with MTX, ADM, and IFO (2nd and 3rd studies). In the chemotherapeutic protocol that involved 3 drugs the percentage of "good histological responses to chemotherapy" (defined as tumor necrosis > 90%) was significantly higher in the 40 patients who were administered CDP by intra-arterial infusion as compared to that observed in the 39 patients treated with CDP by intravenous route (78% versus 46%: P .004). In the two sequential studies where 4 drugs were used, the percentage of good histological responses was essentially the same for patients treated with CDP administered intravenously, and for those treated with CDP administered intra-arterially (78% versus 84%). Regardless of the route of infusion used to administer cisplatinum the percentage of "good" histological responses was significantly higher in the 109 patients treated with the 4-drug protocol as compared to the 79 patients treated with the 3-drug protocol (82% vs 62%; P .04). This difference may essentially be attributed to the higher percentage of good responses observed in the 4-drug protocol in patients treated with CDP administered intravenously (78% vs 46% for patients treated i.v. with the 3-drug protocol; P .006). For the patients instead treated with CDP administered intra-arterially the percentage of good responses was essentially the same with the 4-drug protocol and with the 3-drug protocol (84% vs 78%; P ns). These data lead us to conclude that in the neoadjuvant treatment of osteosarcoma of the limbs a preoperative 4-drug protocol (MTX, CDP, ADM, IFO) is more effective than a 3-drug protocol (MTX, CDP, ADM), and that in a 4-drug preoperative chemotherapy protocol intra-arterial infusion of CDP does not offer particular advantages as compared to intravenous infusion.

Adolescent↗

PubMedDate not supplied

Nitrate tolerance in patients with effort angina.

BACKGROUND: In some patients with chronic stable angina the beneficial effects of nitrates may result not only from a reduction in venous return, but also from their action on coronary circulation. In these patients, rate-pressure product at ischemia (RPPI) increases to > 2500 bpm x mmHg after sublingual nitrates (SLN). The relative susceptibility of the venous system and the coronary circulation to the development of nitrate tolerance and the effects of two different drug schedules on the development of tolerance were investigated in patients with these characteristics. METHODS: Five patients were treated with isosorbide-5-mononitrate (IS5MN) 20 bid (8.00 am and 3.00 pm) for 1 week (Group 1) and 5 patients with IS5MN 40 bid (8.00 am and 8.00 pm) for 1 week (Group 2). Tolerance was identified as the decreased effect of SLN; the effects of nitrates were evaluated in relation to: reduction in left ventricle area (delta LVA), which had been measured using equilibrium radionuclide ventriculograms in LAO 45 degrees; this area was considered as an index of the venous return effects; increase in RPPI (delta RPPI), which had been assessed by ergometric test; RPPI was considered an index of coronary flow reserve. Measurements of LVA and RPPI were made in wash-out at the start of the study (delta LVA 1 and delta RPPI 1) and after 1 week of treatment (delta LVA 2 and delta RPPI 2). The mean values of the differences were then evaluated and compared using Student's "t" test. RESULTS AND CONCLUSIONS: In Group 1 patients delta LVA 2 and delta RPPI 2 showed values which were similar to delta LVA 1 and delta RPPI 1 (mean value delta LVA 2 47 vs mean delta LVA 1 48.2 pixels, p = ns; mean value delta RPPI 2 5264 vs mean delta RPPI 1 5536 bpm x mmHg, p = ns). These results suggest that Group 1 patients did not develop tolerance either at the coronary or at the venous level. In Group 2 patients, delta LVA 2 was significantly lower than delta LVA 1 (mean delta LVA 2 18.4 vs mean delta LVA 1 54 pixels, p < 0.01). This finding indicated tolerance to nitrates at the venous level. On the other hand, in all Group 2 patients, values of delta RPPI 2, though lower than delta RPPI 1 (mean delta RPPI 2 3095 vs mean delta RPPI 1 6083 bpm x mmHg, p < 0.01) were still higher than 2500 bpm x mmHg, indicating that the effect of nitrates at the coronary level was preserved. These data suggest that in patients treated with high doses of nitrates, the effect of these drugs at the coronary level is still present when tolerance has already developed at the venous level.

Angina Pectoris↗

PubMedDate not supplied

[Local recurrence after surgical or surgical-chemotherapeutic treatment of osteosarcoma of the limbs. Incidence, risk factors and prognosis].

METHODS: Local recidivation (incidence, risk factors an prognosis) was analysed retrospectively in 765 patients with non-metastatic osteosarcoma of the extremities treated between 1972 and 1992 either with surgery alone (78 cases) or with surgery and associated adjuvant (258 cases) and neoadjuvant chemotherapy (429 cases). RESULTS: The local recurrence of the disease, which was documented in 26 patients (3.4%), was significantly related to the type of surgery performed (1.1% in 344 amputated patients vs 5.2% in 422 patients treated with resection; p < 0.003) and with surgical margins (0.6% in 700 radical or extensive operations vs 22.7% in 66 marginal or intralesional interventions; p = 0.0001). In patients treated with neoadjuvant chemotherapy, the incidence of local recidivation was also correlated with the type of histological response to chemotherapy (2.9% in 274 cases with a "good" response vs 8.4% in 154 cases with a "poor" response; p < 0.021). In all 26 patients local recidivation was associated with metastases occurring before (16 cases), after (3 cases) or in concomitance (7 cases) with the local recurrence of neoplasia. In spite of treatment performed at the start of recidivation, 25 patients (96.1%) died from the tumour whereas the mortality rate in those patients with metastases but no local recidivation was only 72.1% (261 out of 362 cases). This difference was also statistically significant (p < 0.01). CONCLUSIONS: The results obtained appear to justify the current trend of minimising demolitive surgery in osteosarcoma of the extremities. Surgery should only be performed in these patients by centres able to make an adequate evaluation of surgical margins and the histological response to preoperative chemotherapy. In view of the fatal prognosis linked to recidivation and the high probability of its onset in cases with inadequate surgical margins and a poor response to chemotherapy, the authors propose that subsequent amputation should be performed immediately in those patients undergoing resection who present both these conditions.

Bone Neoplasms↗