RESUMEN
BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).
Asunto(s)
Fibrosarcoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/genética , Fibrosarcoma/enzimología , Fibrosarcoma/genética , Fibrosarcoma/patología , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/enzimología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Quinasas/metabolismo , Neoplasias de la Lengua/enzimología , Neoplasias de la Lengua/patologíaRESUMEN
BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).
Asunto(s)
Fibrosarcoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Resistencia a Antineoplásicos , Fibrosarcoma/genética , Fibrosarcoma/patología , Humanos , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Terapia RecuperativaRESUMEN
PURPOSE: Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis. PATIENTS AND METHODS: Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS. RESULTS: Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis. At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival. CONCLUSION: Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin.
Asunto(s)
Quimioradioterapia/métodos , Osteosarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/mortalidad , Niño , Supervivencia sin Enfermedad , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Osteosarcoma/mortalidad , Osteosarcoma/terapia , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/terapia , Carga Tumoral , Adulto JovenRESUMEN
BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Neoplasias Óseas/cirugía , Niño , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Terapia Neoadyuvante , Osteosarcoma/cirugía , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Calidad de Vida , Proyectos de Investigación , Adulto JovenRESUMEN
Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Adolescente , Adulto , Edad de Inicio , Neoplasias Óseas/epidemiología , Neoplasias Óseas/terapia , Consenso , Humanos , Osteosarcoma/epidemiología , Osteosarcoma/terapia , Sarcoma de Ewing/epidemiología , Sarcoma de Ewing/terapia , Adulto JovenRESUMEN
BACKGROUND: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. PATIENTS AND METHODS: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. RESULTS: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. CONCLUSIONS: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.
Asunto(s)
Recurrencia Local de Neoplasia/prevención & control , Osteosarcoma/cirugía , Adolescente , Adulto , Anciano , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical oncologists, surgeons, pathologists and radiologists. Therefore, therapy should be performed in specialized centers able to provide access to the full spectrum of care. As in other rare malignancies, treatment should be administered within prospective multicenter trials. Therapy must include complete surgical removal of all detectable tumor sites as well as multiagent chemotherapy. The chemotherapy regimen should include several or all of the following four drugs: doxorubicin, high-dose methotrexate with leukovorin-rescue, cisplatin and ifosfamide. Preoperative (neoadjuvant) plus postoperative (adjuvant) polychemotherapy should be preferred, because it allows preparation for safe surgery and preparation of the appropriate prosthesis for the individual patient. The choice of the postponed definitive surgical procedure should be influenced by the anatomical site of the primary tumor, its relationship to neighboring structures, such as vessels and nerves, age and growth potential of the patient, and probably also by the response of the tumor to preoperative chemotherapy. A major, as yet unsolved, problem is the dismal prognosis for patients with unresectable or relapsed osteosarcomas. Novel approaches are needed in order to improve their prognosis.
Asunto(s)
Neoplasias Óseas/terapia , Osteosarcoma/terapia , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/etiología , Neoplasias Óseas/patología , Terapia Combinada , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias/métodos , Osteosarcoma/diagnóstico , Osteosarcoma/etiología , Osteosarcoma/patología , Pronóstico , RecurrenciaRESUMEN
In comparison to cancer in adults, virtually all cancers of childhood and adolescence are rare. Nevertheless, there is a rather ill-defined group of tumors that are not only exceptionally rare but also do not fall into the major clinical categories of childhood cancers. Thus, a substantial proportion of these exceptionally rare tumors are not registered within clinical registries or prospective therapy optimization studies. Only recently, major attention has been drawn to the diagnostic assessment and treatment of children and adolescents with such orphan diseases. In 2006, the RARE TUMOR GROUP has been established within the German Society of Pediatric Oncology and Hematology (GPOH). This working group includes experts from Pediatric Oncology, Pediatric Surgery, Pediatric Pathology, Medical, Dermatologic and Radiation Oncology as well as Pediatric Epidemiology. The major aim of the rare tumor group is to integrate these patients into the diagnostic and therapeutic network successfully established in the pediatric oncologic society. Thus, the group aims at fostering the exchange of experience in the treatment of rare tumors between medical centers and to include patients in the diagnostic and therapeutic reference network. In addition, an information platform shall be established that will be accessible to treating physicians, patients and their parents. More information and better registration shall be established by active data accrual on a regular basis and by the implementation of a data base including diagnostic and therapeutic data of patients with rare tumors. These efforts as presented in this article as well as an intensified international collaboration will allow us to provide children and adolescents with rare tumors the best possible care.
Asunto(s)
Sistemas de Información/organización & administración , Comunicación Interdisciplinaria , Neoplasias/diagnóstico , Enfermedades Raras/diagnóstico , Sistema de Registros , Sociedades Médicas/organización & administración , Adolescente , Niño , Conducta Cooperativa , Alemania , Humanos , Neoplasias/terapia , Enfermedades Raras/terapiaRESUMEN
Data on 5572 children and adolescents diagnosed with malignant bone tumours (International Classification of Childhood Cancer, Group VIII) before the age of 20 years during 1978-1997 in Europe were extracted from the Automated Childhood Cancer Information System (ACCIS) database. Age-standardised incidence among children during the period 1988-1997 was similar for boys and girls aged 0-14 years (5.5-5.6 per million). Among adolescents aged 15-19 years, males had higher incidence (19.3 per million) than females (10.7 per million). Among children, osteosarcoma accounted for 51% of registrations and Ewing's sarcoma for 41%. Among adolescents, 55% of registrations were osteosarcoma and 28% Ewing's sarcoma. Both tumours had their highest incidence in late childhood or early adolescence. There were no significant time trends in incidence during 1978-1997. Five-year survival estimates for patients diagnosed during 1988-1997 were, respectively, 59% and 51% among children and adolescents with osteosarcoma and 62% and 30% among children and adolescents with Ewing's sarcoma. Between 1978-1982 and 1993-1997, survival increased for both children and adolescents with osteosarcoma, and for children with Ewing's sarcoma.
Asunto(s)
Neoplasias Óseas/epidemiología , Bases de Datos Factuales/estadística & datos numéricos , Adolescente , Adulto , Neoplasias Óseas/mortalidad , Niño , Preescolar , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Sistema de Registros/estadística & datos numéricos , Análisis de SupervivenciaRESUMEN
Osteosarcoma, one of the most frequent secondary malignancies after the treatment of young patients with cancer, has only very rarely been observed in association with hematopoietic stem cell transplantation (HSCT). We report four patients who were identified by searching the database of the Cooperative Osteosarcoma Study Group (COSS) for patients whose osteosarcoma arose following HSCT. Transplant indications had been acute lymphoblastic leukemia (3). and sickle cell disease (1). and the stem cell source was bone marrow in all cases (three allogeneic, one syngeneic). All four had received chemotherapy with alkylators as part of their conditioning regimen and/or first line therapy. The conditioning regimen included total body irradiation in three patients. The osteosarcomas arose at the age (adolescence) and sites (around the knee) typical for the disease. All four patients received chemotherapy as part of multimodal osteosarcoma treatment, and all four are currently alive, three in continuous remission at 5 7/12, 2 11/12, and 0 6/12 years and one with relapsed osteosarcoma at 4 1/12 years. One of the osteosarcoma-free survivors suffered a third malignancy, myelodysplastic syndrome. Osteosarcoma should be included among the secondary malignancies that can arise following HSCT. Multi-modal therapy according to guidelines for de novo osteosarcoma can lead to long-term survival in selected patients.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Médula Ósea/efectos adversos , Neoplasias Óseas/etiología , Neoplasias Primarias Secundarias/etiología , Osteosarcoma/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Anemia de Células Falciformes/complicaciones , Niño , Femenino , Prueba de Histocompatibilidad , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicacionesRESUMEN
In an effort to learn more about malignant fibrous histiocytoma (MFH) of bone and its prognosis with different treatment approaches, the European Musculo-Skeletal Oncology Society (EMSOS) initiated a retrospective survey among its members. Data requested included patient and treatment variables and outcome. The information on all patients with histologically proven, primary, localized osseous extremity MFH was analyzed if surgical tumor removal was performed and disease status was documented for at least one follow-up date. 125 such patients were evaluable (74 male, 51 female; median age 34 years; tumor site femur 81, tibia 26, humerus 12, other 6). Local treatment was surgery only (110) or surgery plus radiotherapy (15). Chemotherapy was used in 97/125. On last follow-up, 85 patients remained in remission, 33 had developed metastases, 6 a local recurrence, and 1 a combined relapse. With a median follow-up of 3.9 years for patients at risk, actuarial 5-year disease-free survival was 59%. In univariate analyses, younger age and the use of chemotherapy were associated with a more favorable outcome, as was limb-salvage surgery. 23 of 66 tumors with information on response to preoperative chemotherapy responded well (> 90% necrosis). Among these 23, only one relapsed.
Asunto(s)
Neoplasias Óseas , Histiocitoma Fibroso Benigno , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/cirugía , Niño , Femenino , Histiocitoma Fibroso Benigno/tratamiento farmacológico , Histiocitoma Fibroso Benigno/mortalidad , Histiocitoma Fibroso Benigno/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: The prognosis of osteosarcoma occurring as a second malignant disease (OS-SMD) is thought to be poor. We attempted to evaluate whether this holds true when OS-SMD is treated with combined modality therapy as developed for primary osteosarcoma and if factors that influence survival might be identified. PATIENTS AND METHODS: All patients with OS-SMD registered at the Cooperative German-Austrian-Swiss Osteosarcoma Study Group (COSS) study center between 1980 and June 1996 were evaluated for patient- and treatment-related factors, local and systemic outcome, and survival. Therapy was to be given according to contemporary COSS protocols for primary extremity osteosarcoma, including surgery and multiagent chemotherapy. RESULTS: Thirty patients with OS-SMD were registered (median latency period, 9 years 2 months). The first malignancies had been retinoblastoma (10 patients), sarcoma (10 patients), lymphoma (five patients), carcinoma (four patients), and medulloblastoma (one patient). Treatment for these malignancies had included radiotherapy in 24 patients, surgery in 20, and chemotherapy in 14. Twelve osteosarcomas were located axially and 18 were located in an extremity; 17 were radiation-related. Twenty-seven patients presented with localized disease; three presented with primary metastases (two skip, one lung). All 30 patients received chemotherapy, 29 with multiple drugs. Twenty-eight patients underwent operation. At 7 years, actuarial overall survival, survival free from osteosarcoma progression, and survival free from progression of any cancer were 50%, 34%, and 30%, respectively. In 24 patients with local tumor control, the corresponding values were 63%, 46%, and 38%. All seven local failures occurred in patients with axial osteosarcomas who did not undergo operation with wide surgical margins. CONCLUSION: Provided that local tumor control is achieved, OS-SMD treated with combined modality therapy may have a prognosis that approaches that of otherwise comparable primary osteosarcoma.
Asunto(s)
Neoplasias Óseas/terapia , Neoplasias Primarias Secundarias/terapia , Osteosarcoma/terapia , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Neoplasias Óseas/patología , Distribución de Chi-Cuadrado , Niño , Preescolar , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/patología , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Ifosfamida/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Adolescente , Adulto , Brazo/patología , Brazo/cirugía , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Preescolar , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Infusiones Intraarteriales , Infusiones Intravenosas , Pierna/patología , Pierna/cirugía , Masculino , Metotrexato/administración & dosificación , Terapia Neoadyuvante , Osteosarcoma/patología , Osteosarcoma/cirugía , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Metotrexato/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Esquema de Medicación , Humanos , Metotrexato/uso terapéuticoAsunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Insuficiencia Cardíaca/inducido químicamente , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Sarcoma/tratamiento farmacológicoRESUMEN
Resistance to the classical anthracyclines may be due to one or several mechanisms, most notably p-glycoprotein (pGP) associated multidrug resistance (mdr1, "typical mdr") and altered activity of topoisomerase II (topo II) ("atypical mdr"). Modulators of mdr1 will be of limited value in case of combined forms of resistance. A Friend murine erythroleukemia cell line (F4-6R) carrying both mdrl and topo II mediated anthracycline resistance was used to determine the efficacy of structurally altered anthracyclines against such extended multidrug resistance. Proliferation assays showed that 3'N-morpholinyl substituted anthracyclines were able to retain much of their activity even in this setting. MX2 (KRN8602; 3'-deamino-3'-[4-morpholinyl]-13-deoxo-10-hydroxycarminomycin+ ++), which is 9-alkylated in addition to carrying a 3'N-morpholinyl group, was the most promising agent tested.