المؤلفون: Ferrari S; Istituto Ortopedico Rizzoli, Bologna, Italy. stefano.ferrari@ior.it, Ruggieri P, Cefalo G, Tamburini A, Capanna R, Fagioli F, Comandone A, Bertulli R, Bisogno G, Palmerini E, Alberghini M, Parafioriti A, Linari A, Picci P, Bacci G

المصدر: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2012 Jun 10; Vol. 30 (17), pp. 2112-8. Date of Electronic Publication: 2012 May 07.

نوع المنشور: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Bone Neoplasms/*drug therapy , Chemotherapy, Adjuvant/*methods , Cisplatin/*administration & dosage , Doxorubicin/*administration & dosage , Ifosfamide/*administration & dosage , Methotrexate/*administration & dosage , Osteosarcoma/*drug therapy, Adolescent ; Adult ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Femur/pathology ; Humans ; Humerus/pathology ; Male ; Tibia/pathology

مستخلص: Purpose: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity.
Patients and Methods: Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS).
Results: From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B.
Conclusion: IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.

المؤلفون: Longhi A; Musculoskeletal Department, Istituto Ortopedico Rizzoli, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna, Italy. alessandra.longhi@ior.it, Errani C, Battaglia M, Alberghini M, Ferrari S, Mercuri M, Molinari M

المصدر: Ear, nose, & throat journal [Ear Nose Throat J] 2011 Jun; Vol. 90 (6), pp. E11-5.

نوع المنشور: Case Reports; Journal Article; Review

بيانات الدورية: Publisher: SAGE Publications Country of Publication: United States NLM ID: 7701817 Publication Model: Print Cited Medium: Internet ISSN: 1942-7522 (Electronic) Linking ISSN: 01455613 NLM ISO Abbreviation: Ear Nose Throat J Subsets: MEDLINE

مواضيع طبية MeSH: Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use , Antimetabolites, Antineoplastic/*therapeutic use , Antineoplastic Agents, Phytogenic/*therapeutic use , Fibromatosis, Aggressive/*drug therapy , Indomethacin/*therapeutic use , Methotrexate/*therapeutic use , Vinblastine/*therapeutic use, Adult ; Drug Therapy, Combination ; Female ; Fibromatosis, Aggressive/diagnosis ; Fibromatosis, Aggressive/pathology ; Humans ; Neck/pathology

مستخلص: Aggressive fibromatosis (desmoid tumor) of the neck is rare. When feasible, surgery is the best treatment option. However, complete excision with negative margins is not possible in most cases because of the involvement of vascular and nervous structures. Also, surgery results in poor functional and aesthetic outcomes. Sometimes debulking surgery with positive margins is performed, but the anatomy of the neck is a challenge for oncologic surgeons, and recurrences are not uncommon. Radiotherapy is seldom employed for the same reasons. On the other hand, systemic treatment with chemotherapy, hormone therapy, and noncytotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) has been used with good results. We report a case of inoperable aggressive fibromatosis of the neck that was successfully treated for about 21 months with a combination of chemotherapy and the NSAID indomethacin. As far as we know, this is the first reported use of a combination of chemotherapy and an anti-inflammatory drug in the treatment of aggressive fibromatosis of the neck. We also review the literature on cases of aggressive fibromatosis of the neck that have been reported over the past 12 years.

المؤلفون: Scionti I; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Michelacci F; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Pasello M; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Hattinger CM; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Alberghini M; Servizio di Anatomia Patologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Manara MC; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Bacci G; Sezione di Chemioterapia, Istituti Ortopedici Rizzoli, Bologna, Italy., Ferrari S; Sezione di Chemioterapia, Istituti Ortopedici Rizzoli, Bologna, Italy., Scotlandi K; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Picci P; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy., Serra M; Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy. Electronic address: massimo.serra@ior.it.

المصدر: Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2008 Aug; Vol. 19 (8), pp. 1500-1508. Date of Electronic Publication: 2008 Apr 02.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 9007735 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-8041 (Electronic) Linking ISSN: 09237534 NLM ISO Abbreviation: Ann Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Genes, myc*, Bone Neoplasms/*drug therapy , Bone Neoplasms/*genetics , Methotrexate/*pharmacology , Osteosarcoma/*drug therapy , Osteosarcoma/*genetics , Tetrahydrofolate Dehydrogenase/*genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis ; Adult ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bone Neoplasms/enzymology ; Bone Neoplasms/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Gene Expression/drug effects ; Humans ; Immunohistochemistry ; Methotrexate/therapeutic use ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/pharmacology ; Osteosarcoma/enzymology ; Osteosarcoma/pathology ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/biosynthesis ; Proto-Oncogene Proteins c-myc/genetics ; Tetrahydrofolate Dehydrogenase/biosynthesis

مستخلص: Background: Aims of this study were the validation of C-MYC involvement in methotrexate (MTX) resistance and the assessment of clinical impact of C-MYC and dihydrofolate reductase (DHFR) in osteosarcoma (OS).
Materials and Methods: The involvement of C-MYC in MTX resistance was validated with an antisense approach. C-MYC and DHFR protein levels at diagnosis were assessed by immunohistochemistry on series of patients treated with either a MTX-based protocol (IOR/OS-1; 72 patients) or with a standard four-drug regimen (ISG/SSG 1; 61 patients).
Results: Down-regulation of C-MYC significantly decreased the MTX resistance level of OS cells, demonstrating its causal involvement in this phenomenon. In clinical samples, a worse outcome was associated with increased levels of DHFR and C-MYC at diagnosis in the IOR/OS-1 patients and of C-MYC in the ISG/SSG 1 patients.
Conclusions: Meanwhile the adverse clinical impact of DHFR overexpression appeared to be closely related to the relevance of MTX in the chemotherapeutic protocol, that of C-MYC overexpression was more general and not strictly MTX related. The assessment of C-MYC and DHFR at diagnosis, together with that of other known prognostic markers, can be considered for an early identification of subgroups of OS patients with higher risk of adverse outcome.

المؤلفون: Comandone A; Divisione di Oncologia Medica, Ospedale Gradenigo, Torino, Italy., Passera R, Boglione A, Tagini V, Ferrari S, Cattel L

المصدر: Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2005; Vol. 44 (4), pp. 406-11.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Medical Journals Sweden AB Country of Publication: England NLM ID: 8709065 Publication Model: Print Cited Medium: Print ISSN: 0284-186X (Print) Linking ISSN: 0284186X NLM ISO Abbreviation: Acta Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Bone Neoplasms/*metabolism , Methotrexate/*pharmacokinetics , Osteosarcoma/*metabolism, Adolescent ; Adult ; Area Under Curve ; Bone Neoplasms/diagnosis ; Bone Neoplasms/drug therapy ; Dose-Response Relationship, Drug ; Female ; Humans ; Infusions, Intravenous ; Male ; Maximum Tolerated Dose ; Methotrexate/therapeutic use ; Neoadjuvant Therapy ; Osteosarcoma/diagnosis ; Osteosarcoma/drug therapy ; Prognosis ; Survival Rate

مستخلص: High dose methotrexate (HDMTX) with folinic acid rescue is widely used to treat osteosarcoma, which predominantly afflicts children; the study investigated HDMTX pharmacokinetics (pk) in adult subjects in neoadjuvant/adjuvant settings. Twenty five patients with advanced osteosarcoma (11 females--14 males, median age 26.0 years) were treated by 12 g/m2 HDMTX 4 hour iv infusion (64 total courses, range 1-7 courses). Pk was determined by non-compartmental analysis and population pk modeling. Median (range) bioavailability pk parameters were: C(max) (maximum MTX concentration) 1149.5 microM (692-2,200), AUC(tot) (total area under curve) 6,955.1 micromol*h/l (3,477-12,681). C(max)>1,000 microM gave increased histological responses (p < 0.05). Six covariates (height-weight-hemoglobin-AST-ALT-creatinine) were found to influence MTX volume of distribution (V) and elimination rate constant (K(el)). Toxicity was mild: only two reversible G4 events were observed, related to AUC(tot) >12,000 micromol*h/l (p < 0.001). HDMTX pk and interpatient variability in adults are comparable to those in children. No correlation between C(max)/AUC(tot) and subject age/sex was found, even in the population pk model. The excretion mechanism is not affected by sex/age differences. HDMTX can safely be administered to adults: as in younger patients, a good clinical response can be predicted by C(max), while severe toxicity depends on highest AUC(tot) values.

المؤلفون: Widemann BC; Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1920, USA. bw42y@nih.gov, Balis FM, Kempf-Bielack B, Bielack S, Pratt CB, Ferrari S, Bacci G, Craft AW, Adamson PC

المصدر: Cancer [Cancer] 2004 May 15; Vol. 100 (10), pp. 2222-32.

نوع المنشور: Journal Article; Meta-Analysis

بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 0374236 Publication Model: Print Cited Medium: Print ISSN: 0008-543X (Print) Linking ISSN: 0008543X NLM ISO Abbreviation: Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Acute Kidney Injury/*chemically induced , Antimetabolites, Antineoplastic/*adverse effects , Kidney/*drug effects , Methotrexate/*adverse effects , Osteosarcoma/*drug therapy, Acute Kidney Injury/drug therapy ; Acute Kidney Injury/physiopathology ; Antimetabolites, Antineoplastic/administration & dosage ; Bone Neoplasms/drug therapy ; Humans ; Kidney/physiopathology ; Methotrexate/administration & dosage ; Renal Dialysis ; gamma-Glutamyl Hydrolase/therapeutic use

مستخلص: Background: High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2.
Methods: The literature was reviewed for osteosarcoma trials, use of dialysis-based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate-release trial.
Results: Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade >/= 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods.
Conclusions: HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently.
(Copyright 2004 American Cancer Society.)

المؤلفون: Bacci G; Department of Musculoskeletal Oncology, Division of Chemotherapy, Istituto Ortopedico Rizzoli, Via Pupilli 1, I-40136 Bologna, Italy. gaetano.bacci@ior.it, Ferrari S, Longhi A, Forni C, Loro L, Beghelli C, Tremosini M, Versari M

المصدر: Oncology reports [Oncol Rep] 2003 Jul-Aug; Vol. 10 (4), pp. 851-7.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: D.A. Spandidos Country of Publication: Greece NLM ID: 9422756 Publication Model: Print Cited Medium: Print ISSN: 1021-335X (Print) Linking ISSN: 1021335X NLM ISO Abbreviation: Oncol Rep Subsets: MEDLINE

مواضيع طبية MeSH: Neoadjuvant Therapy*, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Bone Neoplasms/*metabolism , Methotrexate/*pharmacokinetics , Osteosarcoma/*metabolism, Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bone Neoplasms/drug therapy ; Child ; Child, Preschool ; Cisplatin/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Humans ; Ifosfamide/administration & dosage ; Leucovorin/administration & dosage ; Male ; Metabolic Clearance Rate ; Osteosarcoma/drug therapy ; Retrospective Studies

مستخلص: We retrospectively studied 790 patients with osteosarcoma treated by neoadjuvant chemotherapy at a single institution between 1983 and 2000 according to different protocols, all including a high dose of methotrexate (HDMTX), to determine the incidence of delayed clearance of HDMTX, and identify patients at high risk for this kind of toxicity. Chemotherapy was administered according to 7 different protocols, successively activated, in which HDMTX was associated with other drugs (cisplatin, adriamycin, ifosfamide) in different combinations. The doses of MTX ranged between 7.5 to 12 g/m(2) and patients received from 1 to 10 cycles with MTX for a total number of 4219 cycles. The incidence of delayed clearance of MTX (plasma values of the drug at 24 h >5 microM/l) was 8.6% per patient and 1.6% per cycle of treatment. In 51 cases the delayed clearance of MTX was "mild" (plasma values of MTX at 24 h between 5 and 19 microM/l) and in 18 cases "severe" (plasma values of MTX at the 24 h >20 microM/l). The delayed clearance of MTX was significantly correlated with the age of patients (16% for patients over 20 vs. 6% for younger patients: p=0.0001) and was significantly more frequent during the first cycles of chemotherapy (7% during the first 3 cycles of treatment vs. 2% during subsequent cycles). There was also a significant correlation (p=0.0001) between the plasma values of MTX at the end of the infusion and at 18 h and the delayed clearance of the drug. In addition to support treatment by increased hydration and sodium bicarbonate, all patients who experienced the delayed clearance of MTX were treated solely with a high dose of leucovorin (HDLV), which was started at the first 18 h. Significant neutropenia and/or thrombocythopenia, increase of serum creatinine, mucositis of varying degrees and vomiting occurred in most cases of severe delayed clearance of MTX, but all patients completely recovered. We conclude that in spite of adequate hydration and urine alkalinization and the use of pharmacokinetically guided leucoverin rescue, delayed clearance of MTX may still occur and that its incidence is higher in older patients and during the first cycles of treatment. However, if "rescue" treatment is started early, the consequent morbility is tolerable and these patients can be rescued using only HDLV, without the need for extracorporeal removal.

المؤلفون: Bacci G; Sezione di Chemioterapia dei Tumori dell' Apparato Locomotore, Università di Bologna, Italy., Ferrari S, Picci P, Zolezzi C, Gherlinzoni F, Iantorno D, Cazzola A

المصدر: Journal of chemotherapy (Florence, Italy) [J Chemother] 1996 Dec; Vol. 8 (6), pp. 472-8.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 8907348 Publication Model: Print Cited Medium: Print ISSN: 1120-009X (Print) Linking ISSN: 1120009X NLM ISO Abbreviation: J Chemother Subsets: MEDLINE

مواضيع طبية MeSH: Extremities*, Antimetabolites, Antineoplastic/*blood , Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Bone Neoplasms/*blood , Methotrexate/*blood , Osteosarcoma/*blood, Adolescent ; Antimetabolites, Antineoplastic/administration & dosage ; Bone Neoplasms/drug therapy ; Bone Neoplasms/pathology ; Cisplatin/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Humans ; Male ; Methotrexate/administration & dosage ; Osteosarcoma/drug therapy ; Osteosarcoma/pathology ; Prognosis

مستخلص: The authors investigated the influence of methotrexate (MTX) serum concentration on (histologically evaluated) tumor necrosis, induced by a primary multiagent chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients, preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l) compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600 mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did not reach this value (p < 0.002). At a multivariant analysis including age, sex, tumor site and volume, pretreatment serum alkaline phosphatase and lactic dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the histologic type (telangiectatic osteosarcoma), were independent factors influencing tumor necrosis. The authors conclude that MTX serum peaks significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor necrosis can be obtained in 40% of patients with MTX peak concentrations > or = 700 mumol/l.

المؤلفون: Bacci G; Sezione Chemioterapia dei Tumori dell'Apparato Locomotore, Istituti Ortopedici Rizzoli, Bologna., Picci P, Ferrari S, Sangiorgi L, Mercuri M, Bertoni F, Brach del Prever A, Tienghi A, Mancini A, Comandone A, et. al.

المصدر: La Chirurgia degli organi di movimento [Chir Organi Mov] 1995 Jan-Mar; Vol. 80 (1), pp. 1-10.

نوع المنشور: Clinical Trial; Comparative Study; Journal Article; Multicenter Study

بيانات الدورية: Publisher: Springer Country of Publication: Italy NLM ID: 0372573 Publication Model: Print Cited Medium: Print ISSN: 0009-4749 (Print) Linking ISSN: 00094749 NLM ISO Abbreviation: Chir Organi Mov Subsets: MEDLINE

مواضيع طبية MeSH: Antineoplastic Combined Chemotherapy Protocols/*administration & dosage , Bone Neoplasms/*drug therapy , Cisplatin/*administration & dosage , Doxorubicin/*administration & dosage , Ifosfamide/*administration & dosage , Methotrexate/*administration & dosage , Osteosarcoma/*drug therapy, Adolescent ; Adult ; Bone Neoplasms/mortality ; Bone Neoplasms/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Disease-Free Survival ; Extremities ; Female ; Femoral Neoplasms/drug therapy ; Femoral Neoplasms/mortality ; Femoral Neoplasms/surgery ; Humans ; Male ; Osteosarcoma/mortality ; Osteosarcoma/surgery ; Preoperative Care ; Time Factors

مستخلص: 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.

المؤلفون: Fabbri A; Institute of Internal Medicine, University of Bologna, Italy., Motta E, Ferrari S, Longhi C, Marchi E, Bacci G, Figus E, Marchesini G

المصدر: Journal of internal medicine [J Intern Med] 1994 Aug; Vol. 236 (2), pp. 209-14.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8904841 Publication Model: Print Cited Medium: Print ISSN: 0954-6820 (Print) Linking ISSN: 09546820 NLM ISO Abbreviation: J Intern Med Subsets: MEDLINE

مواضيع طبية MeSH: Antipyrine/*pharmacokinetics , Bone Neoplasms/*metabolism , Galactose/*metabolism , Liver/*drug effects , Methotrexate/*pharmacology , Osteosarcoma/*metabolism, Adolescent ; Adult ; Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bone Neoplasms/drug therapy ; Cisplatin/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Humans ; Liver/metabolism ; Liver Function Tests ; Male ; Methotrexate/administration & dosage ; Osteosarcoma/drug therapy ; Prospective Studies

مستخلص: Objectives: To study the effects of short-term high-dose methotrexate therapy on liver function in patients with osteosarcoma.
Design: Open prospective study.
Setting: Department of Internal Medicine and Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
Subjects: Fourteen patients with osteosarcoma, with no evidence of previous or actual liver disease at the time of diagnosis.
Interventions: All patients received a cumulative dose of 30-57 gm-2 of methotrexate within 6 months as neo-adjuvant chemotherapy (pre- and post-surgery). Each course of chemotherapy included methotrexate at a dose of 8-12 gm-2 and, in addition, adriamycin and cisplatinum.
Main Outcome Measures: Galactose elimination capacity and antipyrine clearance were measured at baseline, after the first course of chemotherapy, at the end of the pre-operative period and at the end of chemotherapy. In each case they were carried out after transaminase levels had returned to normal.
Results: Galactose elimination capacity decreased from 2.45 (+/- 0.48) mM min-1 to 2.04 (+/- 0.60) mM min-1 after the five planned courses of chemotherapy (P = 0.013, Wilcoxon signed-rank test), without any change in routine liver function tests. No differences in antipyrine clearance and half-life were demonstrated (n = 8).
Conclusions: The data are consistent with a decreased reserve capacity of the liver after short-term, high-dose methotrexate. Long-term survivors deserve monitoring of liver function for safer methotrexate use, in the light of progressive dosage increments to improve prognosis in neoplastic diseases.

المؤلفون: Bacci G; Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy., Picci P, Ferrari S, Ruggieri P, Casadei R, Tienghi A, Brach del Prever A, Gherlinzoni F, Mercuri M, Monti C

المصدر: Cancer [Cancer] 1993 Dec 01; Vol. 72 (11), pp. 3227-38.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 0374236 Publication Model: Print Cited Medium: Print ISSN: 0008-543X (Print) Linking ISSN: 0008543X NLM ISO Abbreviation: Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Extremities*/pathology , Extremities*/surgery, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Bone Neoplasms/*drug therapy , Bone Neoplasms/*surgery , Cisplatin/*administration & dosage , Doxorubicin/*administration & dosage , Methotrexate/*administration & dosage , Osteosarcoma/*drug therapy , Osteosarcoma/*surgery, Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bone Neoplasms/pathology ; Cisplatin/adverse effects ; Combined Modality Therapy ; Doxorubicin/adverse effects ; Female ; Femur/pathology ; Femur/surgery ; Humans ; Humerus/pathology ; Humerus/surgery ; Infusions, Intravenous ; Injections, Intra-Arterial ; Male ; Methotrexate/adverse effects ; Neoplasm Recurrence, Local ; Osteosarcoma/pathology ; Osteosarcoma/secondary ; Postoperative Complications ; Preoperative Care ; Remission Induction ; Survival Rate ; Tibia/pathology ; Tibia/surgery

مستخلص: Background: Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments.
Methods: Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs.
Results: Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%.
Conclusions: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.