Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma – A phase II trial of the childhood liver tumour strategy group (SIOPEL)

Zsíros, József; Brugières, Laurence; Brock, Pénélope; Roebuck, Derek J.; Maibach, Rudolf; Child, Margaret; Morland, Bruce; Casanova, Michela; Pariente, D.; Paris, Claudia; Camargo, Beatriz de; Ronghe, Milind; Zimmermann, Arthur; Plaschkes, J.; Czauderna, Piotr; Perilongo, Giorgio

doi:10.1016/j.ejca.2012.06.023

Cited by 53 publications

(55 citation statements)

References 29 publications

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“…This phenomenon is consistent with reported clinical results: several phase II studies showed that irinotecan on HCC patients only had modest anti-tumor activity and significant adverse side effects 40, 41, 42 . However, another phase II study using irinotecan to treat refractory or recurrent hepatoblastoma in children has shown encouraging anti-tumor activity and acceptable toxicity 43 . HN3-PE38 alone or in combination with irinotecan shows tumor regression, thus supporting a novel approach for GPC3-positive liver malignancy therapy.…”

Section: Discussionmentioning

confidence: 99%

Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis

et al. 2015

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Glypican-3 is a cell surface glycoprotein that associates with Wnt in liver cancer. We develop two antibodies targeting glypican-3, HN3 and YP7. The first antibody recognizes a functional epitope and inhibits Wnt signaling, whereas the second antibody recognizes a C-terminal epitope but does not inhibit Wnt signaling. Both are fused to a fragment of Pseudomonas exotoxin A (PE38) to create immunotoxins. Interestingly, the immunotoxin based on HN3 (HN3-PE38) has superior anti-tumor activity as compared to YP7 (YP7-PE38) both in vitro and in vivo. Intravenous administration of HN3-PE38 alone, or in combination with chemotherapy, induces regression of Hep3B and HepG2 liver tumor xenografts in mice. This study establishes glypican-3 as a promising candidate for immunotoxin-based liver cancer therapy. Our results demonstrate immunotoxin-induced tumor regression via dual mechanisms: inactivation of cancer signaling via the antibody and inhibition of protein synthesis via the toxin.

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Section: Discussionmentioning

confidence: 99%

Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis

et al. 2015

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“…Two other previously reported trials for this stage of patient were also equal or slightly better than HDC -3-year survival of 62% and 57% for SIOPEL-3 and SIOPEL-1, respectively. 6,25 The comparison for stage 3 patients was more problematic as there were only 4 such patients in our report. However, their outcome (3/4 long-term survivors) does not look obviously better than that of the 2 most recently published results for stage 3 patients not utilizing HDC: 63% and 68% EFS for 38 and 25 patients, respectively, from the COG and the German group.…”

Section: Discussionmentioning

confidence: 71%

Treatment of Hepatoblastoma With High-dose Chemotherapy and Stem Cell Rescue

Karski

Dvorak

Leung

et al. 2014

Journal of Pediatric Hematology/Oncology

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“…weeks after operation [4]. After the first cycle of chemotherapy, she immediately began suffering from severe headaches and dizziness.…”

Section: Figurementioning

confidence: 98%

“…According to current knowledge, the extent of a recurrent disease is generally assessed by contrastenhanced abdominal CT and/or MRI and chest X-ray. If the chest X-ray shows no metastasis, CT of the thorax is also compulsory [4]. Since delayed treatment of this recurrent pattern could have grave consequences, early detection of CNS recurrence is imperative for patients with increased AFP in spite of not showing any symptoms or signs.…”

Section: Figurementioning

confidence: 98%

Case of Brain Metastasis from Second-Relapsed Pediatric Hepatoblastoma

Zhang

Feng

et al. 2014

Pediatric Hematology and Oncology

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A three-year-old girl presented with a hepatic mass and elevated alpha-fetoprotein (AFP) levels of 54,395 ng/mL. Computer tomography (CT) scan revealed a huge mass in the right lobe of her liver, measuring 92 mm × 73 mm, involving three quadrants of her liver, in addition to multiple enlarged para-aortic lymph nodes. There was no evidence of distant metastasis. A fine-needle biopsy was performed, which confirmed the diagnosis of a mixed type hepatoblastoma (HB). According to the International Childhood Liver Tumor Strategy Group criteria, the condition is considered as a highrisk group and staged as a PRETEXT III tumor [1]. After four cycles of chemotherapy with cisplatin and doxorubincin [2], the tumor was removed radically with tumornegative margin. Two additional cycles of chemotherapy were administered as the AFP remained at normal levels. Four months off chemotherapy, her AFP level was grossly elevated to 2635 ng/mL. Consequent CT scans confirmed local recurrence in her liver without any clues of distant disease. In response to the finding, the patient immediately received the second complete resection with a tumor-negative margin and six cycles of postoperative chemotherapy, comprised of etoposide, ifosfamide, and cisplatin [3]. Her AFP level was decreased to normal within 2 weeks. Thereafter, she remained in remission for nearly 15 months before presenting again with an elevated AFP level. At first, her AFP level mildly increased to 100 ng/mL, then gradually to the highest level of 600 ng/mL within 6 months. During this period, multiple CT scans on her abdomen and lung, and bone scintigraphy tests showed no clue of any recurrence. Twenty-one months after her second operation, the girl developed acute headache whereupon an magnetic resonance image (MRI) was performed, which revealed a cranial space-occupying lesion (Figure 1 A-D). Her AFP levels also rose up to 21,599 ng/mL. The patient underwent craniotomy and the histopathological evaulation identified an epithelial type HB recurrence in the central nervous system (CNS). Chemotherapy with irinotecan (20 mg/m 2 /day, iv, days 1-5) was initiated 2

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Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma – A phase II trial of the childhood liver tumour strategy group (SIOPEL)

Cited by 53 publications

References 29 publications

Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis

Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis

Treatment of Hepatoblastoma With High-dose Chemotherapy and Stem Cell Rescue

Case of Brain Metastasis from Second-Relapsed Pediatric Hepatoblastoma

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