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Lees ook eens deze studie. Is m.i. echt interessant voor mensen met verschillende vormen van sarcomen: Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Abstract staat onderaan dit artikel

7 oktober 2019: Bron: The Lancet

Wanneer kinderen en jongeren tot 21 jaar met een zogeheten rhabdomyosarcoom na succesvolle operatie of bestraling of chemo behandeling in een totale remissie zijn gekomen en daarna als onderhoudsbehandeling 6 kuren krijgen met vinorelbine plus als onderhoudsbehandeling continue cyclofosfamide dan hebben zij grotere kans na 5 jaar nog in leven te zijn ziektevrij dan wanneer na de operatie en postoperatieve chemo deze wordt stopgezet. 

  • This randomized phase III trial evaluated maintenance therapy with vinorelbine and continuous low-dose cyclophosphamide compared with stop therapy among patients with high-risk rhabdomyosarcoma in remission after standard therapy (N = 371).
  • Maintenance therapy was associated with longer 5-year overall survival (86.5% with vs 73.7% without maintenance therapy).

Het volledige studierapport: Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial is tegen betaling in te zien op de website van The Lancet

Hier het abstract van de studie:

Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial

Published:September 24, 2019DOI:https://doi.org/10.1016/S1470-2045(19)30617-5

Summary

Background

For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma.

Methods

RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m 2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m 2, on days 1–28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing.

Findings

Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4–89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6–83·2) with maintenance chemotherapy versus 69·8% (62·2–76·2) without maintenance chemotherapy (hazard ratio 0·68 [95% CI 0·45–1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2–90·9) with maintenance chemotherapy versus 73·7% (65·8–80·1) without (HR 0·52 [95% CI 0·32–0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3–4 leucopenia, 148 (82%) had grade 3–4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved.

Interpretation

Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials.

Funding

Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.

In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis.

ORIGINAL RESEARCH ARTICLE

Front. Immunol., 02 August 2019 | https://doi.org/10.3389/fimmu.2019.01814

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Maria Vela1*David Bueno2Pablo González-Navarro1Ariadna Brito1Lucía Fernández3Adela Escudero4Jaime Valentín1Carmen Mestre-Durán1Marina Arranz-Álvarez5Rebeca Pérez de Diego6,7,8Marta Mendiola9,10José Juan Pozo-Kreilinger9,11 and Antonio Pérez-Martínez2,12*†
  • 1Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
  • 2Pediatric Hemato-Oncology Department, Hospital Universitario La Paz, Madrid, Spain
  • 3H12O-CNIO Hematological Malignancies Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 4Molecular Pediatric Oncology Unit, Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain
  • 5Biobank of Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
  • 6Laboratory of Immunogenetics of Human Diseases, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
  • 7Innate Immunity Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
  • 8CIBER of Respiratory Diseases (CIBERES), Madrid, Spain
  • 9Molecular Pathology and Therapeutic Targets, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
  • 10Molecular Pathology Section, Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain
  • 11Pathology Service, La Paz University Hospital, Madrid, Spain
  • 12Department of Pediatric, Universidad Aut ónoma de Madrid (UAM), Instituto de Investigaci ón Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.


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TCM - Traditionele Chinese >> onderhoudstherapie met vinorelbine >> Ewingsarcoom: Aransa probeert >> Bestraling vooraf aan operatie >> Maagzuurremmers hebben sterk >> Sarcomen - weke delen kanker: >> Eribulin mesylate (Halaven) >> CIRT - carbon ion radiotherapie >> Chemo bij Ewingsarcoma. >> Hyperthermie blijkt uitstekende >>