Disseminated Neuroblastoma in Children Older Than One Year at Diagnosis: Comparable Results With Three Consecutive High-Dose Protocols Adopted by the Italian Co-Operative Group for Neuroblastoma

Bernardi, Bruno; Nicolas, Brigitte; Boni, Luca; Indolfi, Paolo; Carli, Modesto; Montezemolo, Luca Cordero di; Donfrancesco, Alberto; Pession, Andrea; Provenzi, Massimo; Cataldo, Andrea Di; Rizzo, A; Tonini, Gian Paolo; Dallorso, Sandro; Conte, Massimo; Gambini, Claudio; Garaventa, Alberto; Bonetti, F; Zanazzo, Andrea Giulio; D’Angelo, Paolo; Bruzzi, Paolo

doi:10.1200/jco.2003.05.191

Cited by 154 publications

(111 citation statements)

References 27 publications

(10 reference statements)

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…We selected a particularly aggressive tumor line (NXS2) that models neuroblastoma (NB), the most common extracranial solid tumor and the first cause of lethality in preschool-age children. Advanced NB patients, who represent Ϸ50% of the cases, show metastatic dissemination at diagnosis and have a long-term survival rate of only 20% despite aggressive chemotherapy with autologous hematopoietic stem cell support (28,29).…”

Section: Short-term Starvation Prevents the Death Of Mice But Not Of mentioning

confidence: 99%

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Raffaghello

Lee

Safdie

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

509

496

View full text Add to dashboard Cite

Strategies to treat cancer have focused primarily on the killing of tumor cells. Here, we describe a differential stress resistance (DSR) method that focuses instead on protecting the organism but not cancer cells against chemotherapy. Short-term starved S. cerevisiae or cells lacking proto-oncogene homologs were up to 1,000 times better protected against oxidative stress or chemotherapy drugs than cells expressing the oncogene homolog Ras2 val19 . Lowglucose or low-serum media also protected primary glial cells but not six different rat and human glioma and neuroblastoma cancer cell lines against hydrogen peroxide or the chemotherapy drug/ pro-oxidant cyclophosphamide. Finally, short-term starvation provided complete protection to mice but not to injected neuroblastoma cells against a high dose of the chemotherapy drug/prooxidant etoposide. These studies describe a starvation-based DSR strategy to enhance the efficacy of chemotherapy and suggest that specific agents among those that promote oxidative stress and DNA damage have the potential to maximize the differential toxicity to normal and cancer cells.reactive oxygen species ͉ short-term starvation ͉ maintenance mode O ur studies in S. cerevisiae and those of others in worms, flies, and mice have uncovered a strong association between lifespan extension and resistance to oxidative stress (1-6). This resistance is observed in long-lived yeast cells lacking RAS2 and SCH9, the orthologs of components of the human Ras and Akt/S6K pathways (2, 5, 7), and in long-lived worms and mice with reduced activity of homologs of the IGF1 receptor (IGF1R), implicated in many human cancers (8). Notably, the IGF1R functions upstream of Ras and Akt in mammalian cells (3-6). Stress resistance is also observed in model systems in which calorie intake is reduced by at least 30% (9). This reduced calorie intake, also known as calorie restriction (CR) or dietary restriction (DR), has been studied for many years and is known to extend life span in organisms ranging from yeast to mice (10). CR also protects against spontaneous cancers and against carcinogen-induced cancers (10-12), raising the possibility that CR and reduced IGF1 may increase stress resistance by similar mechanisms.Our discovery of the role of Ras2 and Sch9 in the negative regulation of antioxidant and other protective systems together with the association between mutations that activate IGF1R, Ras, or Akt and many human cancers prompted our hypothesis that normal but not cancer cells would respond to starvation or down-regulation of Ras/Akt signaling by entering a stressresistance mode. In fact, one of the major ''hallmarks of cancer cells'' is the self-sufficiency for growth signals (13). In the majority of cancers, this ability to grow or remain in a growth mode even in the absence of growth factors is provided by the hyperactivation of one or several components of the IGF1R, Ras, Akt, and mTor pathways.Here, we tested the hypothesis that short-term starvation (STS) or low glucose/low serum can protect mammalian c...

show abstract

Section: Short-term Starvation Prevents the Death Of Mice But Not Of mentioning

confidence: 99%

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Raffaghello

Lee

Safdie

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

509

496

View full text Add to dashboard Cite

show abstract

“…1 Before the routine use of immunotherapy, 3-5 year progression-free survival (PFS) rates in national studies were 20-40%, [2][3][4][5][6] even with inclusion of patients with what is now known to be intermediate-risk NB. 7 The randomized study of the Children's Oncology Group showed significantly better outcome in patients treated post-ASCT with the anti-G D2 chimeric mAb ch14.18 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-2.…”

Section: Introductionmentioning

confidence: 99%

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

et al. 2015

View full text Add to dashboard Cite

Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-G D2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% § 5% and 48% § 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-G D2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-G D2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population.

show abstract

“…[1][2][3][4][5][6][7][8][9][10][11] Features associated with an improved prognosis include younger age 5,7 and absence of bone marrow involvement at diagnosis, 12 early disease response 13 and a complete or near complete response following induction therapy. 6,7,10,14 A poorer prognosis has been associated with an elevated serum ferritin (4143 ng/ ml), 6 bone and BM metastasis, 6 detectable circulating NB cells at diagnosis, 15,16 persisting skeletal and BM disease at the end of induction therapy, 1,2 circulating NB cells in patients otherwise apparently disease-free 16 and high-level of NB contamination at marrow harvest.…”

Section: Introductionmentioning

confidence: 99%

Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation

Trahair

Vowels

Johnston

et al. 2007

Bone Marrow Transplant

View full text Add to dashboard Cite

Disseminated Neuroblastoma in Children Older Than One Year at Diagnosis: Comparable Results With Three Consecutive High-Dose Protocols Adopted by the Italian Co-Operative Group for Neuroblastoma

Abstract: The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.

Cited by 154 publications

References 27 publications

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation

Contact Info

Product

Resources

About

Disseminated Neuroblastoma in Children Older Than One Year at Diagnosis: Comparable Results With Three Consecutive High-Dose Protocols Adopted by the Italian Co-Operative Group for Neuroblastoma

Abstract: The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.

Cited by 154 publications

References 27 publications

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation

Contact Info

Product

Resources

About

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study