melphalan and Osteosarcoma

Recombinant human tumour necrosis factor (TNF) has a selective effect on angiogenic vessels in tumours. Given that it induces vasoplegia, its clinical use has been limited to administration through isolated limb perfusion (ILP) for regionally advanced melanomas and soft tissue sarcomas of the limbs. When combined with the alkylating agent melphalan, a single ILP produces a very high objective response rate. In melanoma, the complete response (CR) rate is around 80% and the overall objective response rate greater than 90%. In soft tissue sarcomas that are inextirpable, ILP is a neoadjuvant treatment resulting in limb salvage in 80% of the cases. The CR rate averages 20% and the objective response rate is around 80%. The mode of action of TNF-based ILP involves two distinct and successive effects on the tumour-associated vasculature: first, an increase in endothelium permeability leading to improved chemotherapy penetration within the tumour tissue, and second, a selective killing of angiogenic endothelial cells resulting in tumour vessel destruction. The mechanism whereby these events occur involves rapid (of the order of minutes) perturbation of cell-cell adhesive junctions and inhibition of alphavbeta3 integrin signalling in tumour-associated vessels, followed by massive death of endothelial cells and tumour vascular collapse 24 hours later. New, promising approaches for the systemic use of TNF in cancer therapy include TNF targeting by means of single chain antibodies or endothelial cell ligands, or combined administration with drugs perturbing integrin-dependent signalling and sensitizing angiogenic endothelial cells to TNF-induced death.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Apoptosis; Cell Adhesion; Cell Division; Chemotherapy, Cancer, Regional Perfusion; Clinical Trials as Topic; Female; Humans; Inflammation; Integrin alphaVbeta3; Liver Neoplasms; Male; Melanoma; Melphalan; Mice; Mice, Nude; Models, Molecular; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Osteosarcoma; Protein Conformation; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins; Remission Induction; Sarcoma; Soft Tissue Neoplasms; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor-alpha; Xenograft Model Antitumor Assays

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. The efficacy of chemotherapy varies according to the histological type of sarcoma. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy. On the other hand, the efficacy of chemotherapy is not statistically demonstrated in non-round cell sarcomas, e. g., malignant fibrous histiocytoma. Nowadays, several kinds of antitumor agents are usually used for adjuvant chemotherapy, and many authors have reported various kinds of regimens and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate, cyclophosphamide, dacarbazine, vincristine, and actinomycin-D. Recently, high-dose chemotherapy combined with autologous peripheral blood or bone marrow stem cell transplantation has been begun in patients who do not respond to standard chemotherapy, and a better prognosis is expected.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Dactinomycin; Doxorubicin; Drug Administration Schedule; Humans; Ifosfamide; Melphalan; Mesna; Methotrexate; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; Vincristine

There has been a striking improvement in the overall numbers of children and adolescents who become disease-free and remain disease-free as a result of intensive therapy as defined today, for the following cancers: acute nonlymphocytic leukemia (ANLL), non-Hodgkin's lymphoma (NHL), poor risk acute lymphocytic leukemia (ALL), osteosarcoma, and Ewing's sarcoma. The therapy for each of these tumors, with the exception of osteosarcoma, consisted of combination chemotherapy with or without radiotherapy and was started as soon after diagnosis as possible. Aggressive therapy of osteosarcoma has consisted of surgical removal of lung metastases and chemotherapy. Intensive chemotherapy recently has included the use of high doses of certain drugs such as cytosine arabinoside (Ara-C), methotrexate, VP-16-213 and melphalan in the treatment of patients with tumors that are currently difficult to treat.

Topics: Acute Disease; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Etoposide; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Methotrexate; Neoplasms; Osteosarcoma; Risk; Sarcoma, Ewing

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Middle Aged; Osteosarcoma

Topics: Adult; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Cyclophosphamide; Doxorubicin; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Humans; Immunotherapy; Leucovorin; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Prednisone; Rhabdomyosarcoma; Testicular Neoplasms; Thiotepa; Vinblastine; Vincristine

The outcomes of osteosarcoma with poor prognostic factors, such as poor responders, metastatic disease at diagnosis, and relapsed or refractory disease, are poor. We reviewed the clinical records of the patients diagnosed with osteosarcoma at our institute between 2004 and 2018 who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in our institute. Ten patients of osteosarcoma with poor responder, refractory status, and metastatic disease at diagnosis received high-dose chemotherapy followed by ASCT. Four patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of thiotepa and melphalan (MEL). Five patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of intravenous busulfan (BU) and MEL. One patient underwent tandem high-dose chemotherapy followed by ASCT with BU and MEL followed by carboplatin and etoposide. None of the ten patients died of regimen related toxicities. None of the five patients with poor responders who underwent high-dose chemotherapy followed by ASCT as part of consolidation therapy died of disease after ASCT. High-dose chemotherapy followed by ASCT might be effective for poor responders in osteosarcoma.

Topics: Adolescent; Bone Neoplasms; Busulfan; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Osteosarcoma; Retrospective Studies; Thiotepa; Transplantation Conditioning; Transplantation, Autologous

The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.. From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method.. Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.. Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Female; Humans; Lung Neoplasms; Male; Melphalan; Metastasectomy; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Osteosarcoma; Survival Rate; Young Adult

Patients with locally advanced or metastatic/recurrent soft tissue and Ewing's sarcoma (EWS) have few treatment options. The purpose of our phase II study was to assess the feasibility, safety and efficacy of tandem high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) in such patients.. Thirteen patients were enrolled onto this study. The first cycle of HDCT consisted of doxorubicin (150 mg/m(2)) and ifosfamide (14 g/m(2)) mixed with mesna (14 g/m(2)), while the second cycle consisted of melphalan (150 mg/m(2)) and cisplatin (200 mg/m(2)).. Eleven out of 13 patients were able to complete both cycles of HDCT. No treatment-related mortality occurred and grade 3 or 4 toxicity was clinically tolerable. The 5-year progression-free survival (PFS) and overall survival (OS) for all patients was 23% (confidence interval, CI: 0-46%) and 31% (CI: 14-70%), respectively. Out of the four patients still alive, two had EWS and measurable disease at the time of ASCT and achieved a complete remission, remaining progression free 126 and 155 months after ASCT.. Our study demonstrates the feasibility and safety of tandem HDCT in patients with high-risk or metastatic/recurrent sarcoma, with some patients achieving long-term PFS and OS.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Disease Progression; Doxorubicin; Feasibility Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Immunoenzyme Techniques; Male; Melphalan; Mesna; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma; Prognosis; Prospective Studies; Protective Agents; Remission Induction; Rhabdomyosarcoma; Safety; Sarcoma; Sarcoma, Ewing; Survival Rate; Transplantation, Autologous; Treatment Outcome; Young Adult

This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5); no response: 6.7% (n = 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P< 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Histiocytoma, Benign Fibrous; Humans; Melanoma; Melphalan; Microdialysis; Middle Aged; Neoplasms; Osteosarcoma; Treatment Outcome

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Digestive System Diseases; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Melphalan; Neoplasms; Neuroblastoma; Osteosarcoma; Remission Induction; Salvage Therapy; Sarcoma, Ewing; Survival Analysis; Thiotepa; Treatment Outcome

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Middle Aged; Osteosarcoma

Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Dysgerminoma; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Neoplasms; Osteosarcoma; Sarcoma, Kaposi

The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival.. Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion.. Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths.. Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Femoral Neoplasms; Humans; Male; Melphalan; Methotrexate; Osteosarcoma; Stem Cell Transplantation; Treatment Outcome

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Osteosarcoma; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Isolated hepatic perfusion (IHP) with melphalan with or without tumour necrosis factor alpha (TNF-alpha) is currently performed in clinical trials in patients with hepatic metastases. Previous studies led to the hypothesis that the use of TNF-alpha in isolated limb perfusion causes specific destruction of tumour endothelial cells and thereby induces an increased permeability of tumour vasculature. However, whether TNF-alpha contributes to the therapeutic efficacy in IHP still remains unclear. In an in vivo rat liver metastases model we studied three different tumours: colon carcinoma CC531, ROS-1 osteosarcoma and BN-175 soft-tissue sarcoma which exhibit different degrees of vascularisation. IHP was performed with melphalan with or without the addition of TNF-alpha. IHP with melphalan alone resulted, in all tumour types, in a decreased growth rate. However in the BN-175 tumour addition of TNF-alpha resulted in a strong synergistic effect. In the majority of the BN-175 tumour-bearing rats, a complete response was achieved. In vitro cytoxicity studies showed no sensitivity (CC531 and BN-175) or only minor sensitivity (ROS-1) to TNF-alpha, ruling out a direct interaction of TNF-alpha with tumour cells. The response rate in BN-175 tumour-bearing rats when TNF-alpha was coadministrated with melphalan was strongly correlated with drug accumulation in tumour tissue, as only in these rats a five-fold increased melphalan concentration was observed. Secondly, immunohistochemical analysis of microvascular density (MVD) of the tumour showed a significantly higher MVD for BN-175 tumour compared to CC531 and ROS-1. These results indicate a direct relation between vascularity of the tumour and TNF-alpha mediated effects. Assessment of the tumour vasculature of liver metastases would be a way of establishing an indication for the utility of TNF-alpha in this setting.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Cell Division; Chemotherapy, Cancer, Regional Perfusion; Colonic Neoplasms; Disease Models, Animal; Immunoenzyme Techniques; In Vitro Techniques; Liver Neoplasms, Experimental; Male; Melphalan; Microcirculation; Osteosarcoma; Rats; Rats, Inbred BN; Sarcoma; Tissue Distribution; Tumor Necrosis Factor-alpha

Cytokine gene transfer using (multiple) intratumoral injections can induce tumor regression in several animal models, but this administration technique limits the use for human gene therapy. In the present studies we describe tumor growth inhibition of established limb sarcomas after a single isolated limb perfusion (ILP) with recombinant adenoviral vectors harboring the rat IL-3 beta gene (IG.Ad.CMV.rIL-3 beta). In contrast, a single intratumoral injection or intravenous administration did not affect tumor growth. Dose-finding studies demonstrated a dose-dependent response with a loss of antitumor effect below 1 x 10(9) IU of IG.Ad.CMV.rIL-3 beta. Perfusions with adenoviral vectors bearing a weaker promoter (MLP promoter) driving the rIL-3 beta gene did not result in antitumor responses, suggesting that the rIL-3 beta-mediated antitumor effect depends on the amount of rIL-3 beta protein expressed by the infected cells. Furthermore, it was shown by direct comparison that ILP with IG.Ad.CMV.rIL-3 beta in the ROS-1 osteosarcoma model is at least as efficient as the established therapy with the combination of TNF-alpha and melphalan. Treatment with IG.Ad.CMV.rIL-3 beta induced a transient dose-dependent leukocytosis accompanied by an increase in peripheral blood levels of histamine. Leukocyte infiltrations were also histopathologically demonstrated in tumors after perfusion. These results demonstrate that ILP with recombinant adenoviral vectors carrying the IL-3 beta transgene inhibits tumor growth in rats and suggest that cytokine gene therapy using this administration technique might be beneficial for clinical cancer treatment.

Topics: Adenoviridae; Animals; Carrier Proteins; Dose-Response Relationship, Drug; Extremities; Gene Transfer Techniques; Histamine; Leukocytes; Male; Melphalan; Neoplasm Transplantation; Osteosarcoma; Perfusion; Promoter Regions, Genetic; Rats; Receptors, Interleukin-3; Sarcoma; Time Factors; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Isolated perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated kidney perfusion. We studied the feasibility of a perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated kidney perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the kidney to perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated kidney perfusion for human tumours seems, therefore, questionable.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Kidney; Male; Melphalan; Neoplasm Transplantation; Neoplasms, Experimental; Osteosarcoma; Rats; Renal Insufficiency; Shock, Septic; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Isolated limb perfusion (ILP) with TNF alpha, IFN gamma and melphalan causes impressive tumour reduction in patients with irresectable soft tissue sarcomas with a high limb salvage rate. Since this therapy could be of value in patients with progressive osteosarcoma, we performed a study in an osteosarcoma tumour model in the rat. The ROS-1 osteosarcoma was implanted s.c. in the hind leg of WAG rats. Rats were divided in four groups: rats that underwent ILP with perfusate alone, TNF alpha alone, melphalan alone or their combination. Almost all rats, treated with a sham ILP or a perfusion with 40 micrograms melphalan, showed progressive disease (PD) (6/6 and 5/6). After perfusion with 50 micrograms TNF alpha alone a varied response was observed: 2/6 PD, 2/6 no change (NC) and 2/6 a complete remission (CR). After combined perfusion: 3/6 rats had a partial remission and 3/6 a CR. The best and most consistent responses are obtained by combining TNF alpha and melphalan. The discrepancy with the in vitro sensitivity of ROS-1 indicates that indirect effects are important in this tumour model.

Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Melphalan; Osteosarcoma; Perfusion; Rats; Rats, Inbred Strains; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Dacarbazine; Dactinomycin; Evaluation Studies as Topic; Extremities; Humans; Hyperthermia, Induced; Incidence; Melanoma; Melphalan; Neoplasm Metastasis; Osteosarcoma; Rhabdomyolysis; Skin Neoplasms; Treatment Outcome

Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion.

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Infusions, Intravenous; Injections, Intra-Arterial; Melphalan; Neoplasm Staging; Osteosarcoma; Prognosis; Radiotherapy; Survival Rate; USSR; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Dactinomycin; Extracorporeal Circulation; Extremities; Humans; Hyperthermia, Induced; Melanoma; Melphalan; Neoplasm Recurrence, Local; Osteosarcoma; Sarcoma; Soft Tissue Neoplasms; Survival Rate

A 54-year-old man was admitted to our hospital for precise examination of pancytopenia in October 1988. He had been cut off his left femur and irradiated because of osteosarcoma in 1954. After 30 years, he was diagnosed as Waldenström's macroglobulinemia. Melphalan had been given 2 mg daily for 19 months until August 1988, when it was discontinued due to pancytopenia. Peripheral blood showed Hb 6.6 g/dl, platelet 40 x 10(3)/microliters, and WBC 2000/microliters with 33% blasts. Bone marrow showed normocellularity with 36% blasts. Although blasts were negative for peroxidase staining, surface marker analysis revealed myeloid (CD 13, CD 33) phenotypes. Chromosome analysis showed 45, XY, -7, inv (3). A CT scan of the liver showed a mass, 10 by 10 cm, compatible with hepatocellular carcinoma. He was treated with very low dose Ara-C without noticeable effect. Hepatic tumor gradually enlarged, and he died of hepatic failure. This is a rare case of quadruplicate malignancies. The chromosomal abnormality suggests that AML was secondary leukemia which might be associated with immunosuppression due to macroglobulinemia and/or melphalan therapy.

Topics: Carcinoma, Hepatocellular; Femoral Neoplasms; Humans; Leukemia, Myeloid, Acute; Liver Neoplasms; Male; Melphalan; Middle Aged; Neoplasms, Multiple Primary; Osteosarcoma; Waldenstrom Macroglobulinemia

Four patients with osteosarcoma were treated with intensive chemotherapy and autologous bone marrow transplantation (ABMT). The patients received high-dose methotrexate (9-12 mg/m2) with citrovorum factor rescue, high-dose melphalan (60 mg/m2 X 3), actinomycin D (0.5 mg/m2 X 3), adriamycin (30 mg/m2 X 2) and high-dose cyclophosphamide (60 mg/kg X 2) during 4 weeks. Bone marrow was aspirated and cryopreserved before treatment and reinfused 48 hours after the completion of chemotherapy. Two of four patients had advanced osteosarcoma with multiple pulmonary metastasis, one of whom had responded well and achieved partial response while the other had shown no response, and both patients died of disease progression 4 and 11 months after ABMT, respectively. The other two patients who received this regimen at an earlier disease stage for prevention of pulmonary metastasis, are alive and well without any evidence of metastasis 31 and 18 months after ABMT, respectively. This regimen was tolerated well in all patients except for mild nausea and vomiting. No infectious episodes were observed during the period of aplasia which continued for 19 to 38 days after marrow infusion. These results suggest that this supralethal combination chemotherapy is safe and tolerable when used with ABMT and effective for patients with osteosarcoma, especially when applied in the non-metastatic phase.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Humans; Male; Melphalan; Methotrexate; Osteosarcoma; Transplantation, Autologous

Chemotherapeutic agents are used in increasingly high dosages to treat patients with refractory cancers. An in vitro clonogenic assay was used to investigate the effects of melphalan on cultures of human neuroblastoma, Ewing's sarcoma, and osteosarcoma cells, as well as on normal bone marrow cells. A 1-hr incubation with 10(-5) M melphalan significantly inhibited tumor colony growth of both fresh neuroblastoma and osteosarcoma cells (p less than 0.01) while Ewing's sarcoma cells and normal bone marrow appeared resistant to melphalan even at a 100-fold higher concentration. Incubation with melphalan for 8 hr did not significantly increase the sensitivity of neuroblastoma and osteosarcoma or the relative resistance of Ewing's sarcoma cells; however, normal bone marrow which had remained resistant to melphalan after 1 hr of incubation, showed significant inhibition of colony growth after an 8-hr incubation with the agent. Repeated exposure to melphalan increased the degree of inhibition of both tumor and normal marrow colonies. Fresh neuroblastoma cells were significantly more sensitive than long-term cultured neuroblastoma cells at all drug doses tested. HPLC studies demonstrated that the loss of melphalan followed first-order kinetics with a half-life of 69 min, and that in addition to the 2 known breakdown products, mono- and dihydroxy-melphalan, several other peaks were present which were not attributable to the tissue culture medium or the buffer solutions.

Topics: Bone Marrow; Cells, Cultured; Chromatography, High Pressure Liquid; Humans; Melphalan; Neoplasms; Neuroblastoma; Osteosarcoma; Sarcoma, Ewing; Tumor Stem Cell Assay

The aim of this study was to investigate whether the newly synthesized bisphosphonic acid-linked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.

Topics: Animals; Antineoplastic Agents; Body Temperature; Body Weight; Bone and Bones; Bone Development; Bromine; Calcium; Carcinoma 256, Walker; Diphosphonates; Dose-Response Relationship, Drug; Female; Kidney; Male; Melphalan; Mice; Mice, Inbred Strains; Mutagens; Nitrogen Mustard Compounds; Osteosarcoma; Pamidronate; Radioisotopes; Rats; Rats, Inbred Strains; Salmonella typhimurium; Sex Factors; Tissue Distribution

Autologous bone marrow rescue circumvents the major toxicity of most cancer chemotherapeutic agents. Melphalan is a particularly well suited agent for use with autologous bone marrow rescue and produces response in chemo-resistant tumours. Thirteen patients have been treated with high dose melphalan with autologous bone marrow rescue in this department. The aims of treatment were palliation, debulking of non-resectable tumours and curative adjuvant therapy. Three patients died of melphalan related toxicity. Of the remaining ten patients there were five partial remissions, one objective response, one complete remission, one with no response and two patients in whom the response is not yet assessable (adjuvant therapy). In our experience high dose melphalan is an effective means of killing tumour cells which are not sensitive to chemotherapy at conventional doses. It is recommended in young patients who have not had extensive previous radio- or chemotherapy, in the early stages of disease, with cure or prolonged remission the aim. High dose melphalan is not recommended in the older patient or in those with massive diseases and is no longer used with palliative intent.

Topics: Adenocarcinoma; Adolescent; Adult; Bone Marrow Transplantation; Female; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Neoplasms; Osteosarcoma; Pelvic Neoplasms; Teratoma

Carminomycin, a new antibiotic made in the USSR, was used in the treatment of 21 patients aged 5 to 15 years with extended osteogenic sarcoma. As a result of the treatment the number of the patients with lifetime prolonged for 1-2 years increased from 7.6 to 46 per cent. It was shown that the drug might be used for the prophylaxis of the localized forms of the disease in children.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carubicin; Child; Child, Preschool; Combined Modality Therapy; Daunorubicin; Drug Evaluation; Follow-Up Studies; Humans; Lung Neoplasms; Lymphatic Metastasis; Melphalan; Osteosarcoma; Time Factors; Vincristine

A unique case of a 15-year-old boy with complete paraplegia due to the compression of osteogenic sarcoma at the fourth thoracic vertebra is presented. Because of the difficulty of surgical treatment, he was treated merely by the arterial infusion of Adriamycin (doxorubicin) and systemic chemotherapy in conformity with the cyclophosphamide, Oncovin (vincristine), methotrexate, phenylalanine mustard, Adriamycin (doxorubicin) ( COMPADRI )-III regimen. The patient regained normal function, and has been disease-free without any neurologic deficit for 6 years. There appears to be some hope for cure using chemotherapy only in otherwise unpromising patients.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Male; Melphalan; Methotrexate; Osteosarcoma; Spinal Neoplasms; Thoracic Vertebrae; Vincristine

It is axiomatic that a given dose of an antitumor agent will not produce the same effect in 100% of the treated subjects. Numerous explanations regarding the sources of this heterogeneous response to drugs have been offered; however, there is a scarcity of experimental data allowing critical evaluation of the sources of variance. It is possible to study heterogeneous antitumor drug response in experimental, inbred animals. One animal model system, the advanced Ridgway osteogenic sarcoma, exhibits marked variation in its response to maximally tolerated doses of a number of clinically active antitumor agents. To evaluate the role of the host in the variable drug response, the tumor was bilaterally implanted into the flank regions of recipient AKR male mice. Treatment of the advanced tumor (200 mg-1,500 mg) with maximally tolerated doses of vincristine or L-phenylalanine mustard produced marked, but variable antitumor responses. Evaluation of a number of quantal and graded parameters of the chemotherapeutic response suggested that host heterogeneity contributes to variability. The host contribution was more apparent in this experiment model when the agent was noncurative. The underlying biological basis for the host heterogeneity is not known; however, it appears likely that pharmacological, immunological or other differences between the inbred animals account for the heterogeneity. Identification of these factors may be experimentally feasible in this animal model and help in the design of future studies in humans.

Topics: Analysis of Variance; Animals; Dose-Response Relationship, Drug; Male; Melphalan; Mice; Mice, Inbred AKR; Neoplasm Transplantation; Osteosarcoma; Sarcoma, Experimental; Vincristine

Topics: Bone Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Melphalan; Methotrexate; Osteosarcoma; Vincristine

Topics: Adolescent; Bone Marrow Transplantation; Bone Neoplasms; Humans; Humerus; Male; Melphalan; Neoplasms, Multiple Primary; Osteosarcoma; Transplantation, Autologous

Topics: Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Osteosarcoma; Radiotherapy Dosage

Results of surgery and chemotherapy in osteosarcoma are based on a retrospective investigation of 122 patients from 1930 till 1978 treated at the Orthopaedic Department of Vienna University and documented at the Viennese Bone Tumour Registry. Adequate surgery is considered to be the radical elimination of the tumour in an oncological sense, e.g. amputation or resection. Our own patients were examined in this light and different forms of chemotherapy are compared and their efficacy as adjuvant treatment is evaluated. The turning point in the prognosis of osteosarcoma came with the introduction of high-dose methotrexate therapy (HDMTX) in 1972 and which has been employed at the Orthopaedic Department of Vienna University since 1975. So far, HDMTX has been used in the management of 18 patients and the short-term results confirm the excellent results reported in the literature. The consequent change in policy with regard to the current surgical approach to osteosarcoma is discussed in detail.

Topics: Adolescent; Amputation, Surgical; Bone Neoplasms; Child; Cyclophosphamide; Female; Femur; Humans; Humerus; Male; Melphalan; Methotrexate; Mitomycins; Osteosarcoma; Prognosis; Prostheses and Implants; Tibia

New concepts and treatments currently available for adjuvant studies are illustrated by a review of ongoing studies sponsored by the National Cancer Institute. More thorough information is needed on immunotherapeutic agents to allow more rationale in the use of these agents. Solid bases to properly select drugs or drug combinations for adjuvant purposes are being established. However, dose-schedule and duration of treatment are still to be defined. Strategies directed at prolonging the benefit of surgical adjuvant chemotherapy remain to be planned. Progress continuously achieved with immunotherapy and chemotherapy should rapidly broaden the spectrum of tumour types to be included in adjuvant studies.

Topics: Antineoplastic Agents; Breast Neoplasms; Cisplatin; Colonic Neoplasms; Cyclophosphamide; Dianhydrogalactitol; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Melphalan; Methotrexate; Neoplasms; Osteosarcoma; Rectal Neoplasms

Topics: Bleomycin; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Melphalan; Methotrexate; Osteosarcoma; Plasmacytoma; Prednisone; Sarcoma, Ewing; Vincristine

Treatment for primary malignant tumors of bone, in the past several decades, has yielded uniformly poor results. Recent progress in chemotherapy and immunotherapy are detailed. An important advance in treating osteogenic sarcoma has been the application of adjuvant chemotherapy after initial amputation. CONPADRI-I and COMPADRI-II chemotherapy (a multiple drug approach) is discussed. Adriamycin in combination or alone has proved effective in treating osteogenic sarcoma. Ewing's tumor is showing increased survival rates from radiation therapy alone, as well as by use of systemic adjuvant chemotherapy combined with local radiation. Adjuvant triple chemotherapy with radiotherapy has resulted in pronounced improvement in survival. Chondrosarcomas are largely chemotherapy-resistant. Immunotherapy in bone tumors still is in the experimental stage and investigations with immunotherapy are preliminary. It appears, however, that the immunological status of a patient definitely relates to prognosis. Through increased sophistication in specific chemotherapy and magnitude of treatment, further advances in treatment of primary malignant bone tumors may be expected.

Topics: Amputation, Surgical; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Immunity, Active; Immunity, Maternally-Acquired; Immunotherapy; Melphalan; Neoplasm Metastasis; Osteosarcoma; Postoperative Care; Sarcoma, Ewing; Vincristine

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

Forty-three patients with osteosarcoma were treated with amputation and adjuvant chemotherapy utilizing a four-drug combination of cyclophosphamide, vincristine, phenylalanine mustard, and adriamycin (CONPADRI-I regimen). Twenty-four patients (56 per cent) remained free of metastases twelve to sixty-one months after diagnosis. Ten of the twenty-four have been disease-free for more than three years. Another group of thirty patients was treated with amputation and a five-drug adjuvant chemotherapy program which included the administration of massive doses of methotrexate with citrovorum factor (COMPADRI-II regimen). Twenty of the thirty (67 per cent) remained free of metastases from twelve to twenty-six months after amputation (median, sixteen months). Two deaths related to methotrexate toxicity occurred. Late metastases developed in three patients (at sixteen, nineteen, and twenty-six months after operation) in the group treated with the COMPADRI-II regimen.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Melphalan; Methotrexate; Middle Aged; Osteosarcoma; Vincristine

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Femoral Neoplasms; Follow-Up Studies; Frontal Bone; Humans; Humerus; Ilium; Male; Mandibular Neoplasms; Maxillary Neoplasms; Melphalan; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Radiotherapy, High-Energy; Sacrum; Sphenoid Bone; Tibia; Vincristine

Recent advances in the use of chemotherapy for treatment of osteosarcoma have altered out pessimism in this disease. Results are presented from 3 groups of investigators using different agents as adjuvant chemotherapy following immediately upon amputation of the primary. The Roswell Park Memorial Institute began a regime, immediately after amputation, of adriamycin 30 mg/M2 for 3 doses and given every 4-6 weeks. This study was subsequently expanded in a cooperative group (ALGB) and the results on 20 patients analyzed. At 19 months approximately 75 per cent are free of any pulmonary metastases compared with 10-25 per cent expected from amputation alone. Similar results have been obtained by other Centers using different chemotherapeutic agents. In Boston Children's Hospital high dose Methotrexate with citrovorum factor is used. In 12 of these patients local control of the primary by surgery was obtained and of these only 1 developed pulmonary metastases during an observation time of 23 months. At the M. D. Anderson Hospital multi-drug combinations were used including Cyclophosphamide, Vincristine, L-Phenylalamine Mustard and Adriamycin. They reported a survival rate of 55 per cent (10 out of 18). All of these neoplastic agents have toxic side effects but when carefully used these effects are minimized and the quality of life is quite good. Many questions must be answered by future controlled long term follow-up studies.

Topics: Amputation, Surgical; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Lung Neoplasms; Melphalan; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Vincristine

A four-drug adjuvant chemotherapy regimen (CONPADRI-I) was utilized in the primary treatment of 18 children with osteogenic sarcoma. All patients had surgical amputation for the primary lesion. The children then received cyclophosphamide, vincristine, melphalan, and adriamycin in defined combinations intermittently over a 72-week period. Of the 18 patients, 10 (55%) remain free of disease 24 months or longer from time of amputation.

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Heart; Humans; Leukopenia; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Thrombocytopenia; Vincristine

Topics: Adenocarcinoma; Amides; Androstanols; Animals; Antineoplastic Agents; Cricetinae; Cyclohexanes; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Estradiol; Female; Hydroxyurea; Imidazoles; Mammary Neoplasms, Experimental; Melanoma; Melphalan; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Osteosarcoma; Plasmacytoma; Progesterone; Rats; Sarcoma, Experimental; Triazenes

Topics: Bone Neoplasms; Cyclophosphamide; Giant Cell Tumors; Humans; Liver; Melphalan; Osteoma, Osteoid; Osteosarcoma; Radiation Effects; Radiotherapy; Radiotherapy Dosage; Sarcoma; Sarcoma, Ewing

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Child; Chondrosarcoma; Female; Humans; Hypothermia, Induced; Hypoxia; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Methods; Osteosarcoma; Radiation Injuries; Tourniquets

Topics: Adolescent; Amputation, Surgical; Anti-Bacterial Agents; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Child; Chondrosarcoma; Giant Cell Tumors; Hip; Humans; Lymphoma, Large B-Cell, Diffuse; Melphalan; Neoplasm Metastasis; Osteosarcoma; Radioisotopes; Sarcoma, Ewing; Shoulder; Vitamins

Topics: Adolescent; Adult; Bone Marrow; Child; Child, Preschool; Dosage Forms; Female; Humans; Injections, Intravenous; Leukopenia; Male; Melphalan; Neoplasm Metastasis; Osteosarcoma; Thrombocytopenia; Time Factors

Topics: Adolescent; Adult; Autopsy; Child; Child, Preschool; Female; Humans; Male; Melphalan; Mitomycins; Neoplasm Metastasis; Osteosarcoma; Time Factors; Vincristine

Topics: Adolescent; Amines; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Female; Humans; Hydroxyurea; Male; Melphalan; Neoplasm Metastasis; Nitrosourea Compounds; Osteosarcoma; Sarcoma, Ewing; Triazines; Uracil Mustard; Vincristine

Topics: Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Melanoma; Melphalan; Neoplasms; Osteosarcoma; Skin Neoplasms; Thiotepa

Topics: Adolescent; Adult; Aged; Child; Fibrosarcoma; Giant Cell Tumors; Hemangiosarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Maxillary Neoplasms; Melphalan; Middle Aged; Myxosarcoma; Osteosarcoma; Radioisotope Teletherapy; Sarcoma; Thiotepa

Topics: Adenocarcinoma; Ameloblastoma; Antineoplastic Agents; Astrocytoma; Brain Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cyclophosphamide; Ethylenediamines; Facial Neoplasms; Fibrosarcoma; Glioma; Humans; Infusions, Parenteral; Mechlorethamine; Melanoma; Melphalan; Meningioma; Methotrexate; Osteosarcoma; Perfusion; Quinones; Retinoblastoma; Rhabdomyosarcoma; Sarcoma; Thiotepa

Topics: Amputation, Surgical; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Lymph Node Excision; Melanoma; Melphalan; Osteosarcoma; Sarcoma; Thiotepa

Topics: Female; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melphalan; Multiple Myeloma; Neoplasms; Osteosarcoma; Ovarian Neoplasms; Research; Sarcoma; Sarcoma, Ewing; Testicular Neoplasms; Thymoma

Topics: Adolescent; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Child; Chondrosarcoma; Dogs; Femur; Fibula; Hemangiosarcoma; Humans; Melanoma; Melphalan; Mesenchymoma; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Ulna; Uracil

Topics: Aorta; Aorta, Abdominal; Bone Neoplasms; Carotid Arteries; Chemotherapy, Cancer, Regional Perfusion; Chondrosarcoma; Dactinomycin; Dogs; Fibrosarcoma; Iliac Artery; Iliac Vein; Leiomyosarcoma; Liposarcoma; Lymphoma, Non-Hodgkin; Melphalan; Mesothelioma; Neoplasms; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Kaposi; Subclavian Artery; Vena Cava, Inferior

Topics: Bone Neoplasms; Cobalt Isotopes; Dactinomycin; Drug Therapy; Humans; Mandible; Mandibular Neoplasms; Melphalan; Methotrexate; Neoplasms; Osteomyelitis; Osteosarcoma; Pathology; Radiography; Radium; Sarcoma