Ocular Pharmacology of Topotecan and Its Activity in Retinoblastoma

Schaiquevich, Paula; Carcaboso, Ángel M.; Buitrago, Emiliano; Taich, Paula Juliana; Opezzo, Javier A.W.; Bramuglia, Guillermo F.; Chantada, Guillermo

doi:10.1097/iae.0000000000000253

Cited by 40 publications

(25 citation statements)

References 58 publications

(76 reference statements)

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“…Seven patients out of eight received intrathecal thiotepa and one patient received thiotepa during neoadjuvant chemotherapy and topotecan during adjuvant chemotherapy because of a failure to collect peripheral stem cells. Indeed, Schaiquevich et al showed that topotecan, alone or in combination, is active against retinoblastoma and Potter et al showed that intrathecal route of administration is tolerable and active against recurrent or refractory leptomeningeal leukemia. It was therefore used in this patient because we could not intensify treatment with high‐dose chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Management of advanced uni‐ or bilateral retinoblastoma with macroscopic optic nerve invasion

Choucair

Brisse

Fréneaux

et al. 2019

Pediatric Blood & Cancer

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Background Retinoblastoma with macroscopic optic nerve (ON) invasion depicted by imaging at diagnosis remains a major problem and carries a poor prognosis. We sought to describe the treatment and outcome of these high‐risk patients. Methods Retrospective mono‐institutional clinical, radiological, and histological review of patients with uni‐ or bilateral retinoblastoma with obvious ON invasion, defined by radiological optic nerve enlargement (RONE) depicted by computed tomography scan or magnetic resonance imaging (MRI), was performed. Results Between 1997 and 2014, among the 936 patients with retinoblastoma treated at Institut Curie, 11 had detectable RONE. Retinoblastoma was unilateral in 10 and bilateral in one. Median age at diagnosis was 28 months (range, 11‐96). ON enlargement extended to the orbital portion in three patients, to the optic canal in five, to the prechiasmatic portion in two, and to the optic chiasm in one. Nine patients received neoadjuvant chemotherapy and partial response was obtained in all. Enucleation was performed in 10/11 patients—by an anterior approach in three and by anterior and subfrontal approaches in seven. Three patients had a positive ON resection margin (2/3 after primary enucleation). All enucleated patients received adjuvant treatment (conventional chemotherapy: 10, high‐dose chemotherapy: seven, radiotherapy: five). Leptomeningeal progression occurred in four patients. Seven are in first complete remission (median follow up: 8 years [3.5‐19.4]). Conclusion Neoadjuvant chemotherapy and microscopic complete resection have a pivotal role in the management of retinoblastoma with RONE. MRI is recommended for initial and pre‐operative accurate staging. Surgery should be performed by neurosurgeons in case of posterior nerve invasion. Radiotherapy is required in case of incomplete resection.

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Section: Discussionmentioning

confidence: 99%

Management of advanced uni‐ or bilateral retinoblastoma with macroscopic optic nerve invasion

Choucair

Brisse

Fréneaux

et al. 2019

Pediatric Blood & Cancer

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“…Finally, as previously published, we highlight the activity and safety of intrathecal topotecan for high‐risk retinoblastoma with CSF involvement included in this multimodality treatment . We selected intrathecal topotecan based on its activity in retinoblastoma and previous reports for intrathecal use …”

Section: Discussionmentioning

confidence: 94%

Combined high‐dose intra‐arterial and intrathecal chemotherapy for the treatment of a case of extraocular retinoblastoma

Rodriguez

Zugbi

Requejo

et al. 2018

Pediatric Blood & Cancer

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Patients with retinoblastoma and central nervous system (CNS) involvement are rarely curable with available treatments. We designed a high-dose intra-arterial regimen targeting the ophthalmic artery and chiasm combined with intrathecal chemotherapy to treat a 4-year-old patient with retinoblastoma metastasized to the CNS. After three cycles of this regimen, including carboplatin, melphalan, and intrathecal topotecan, a partial response of the orbital tumor mass and chiasmatic lesion, and complete response in the cerebrospinal fluid and bone marrow were achieved. This new treatment strategy may be explored as a treatment component for patients with overt extraocular retinoblastoma and CNS dissemination.

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“…6). These findings may help to explain why CPT and another TOP1 inhibitor, topotecan, were found to have potent and fast activity against retinoblastoma, which is caused by the loss of RB function (Chantada et al, 2009;Han and Wei, 2011;Schaiquevich et al, 2014). In the Arabidopsis root, further work is needed to reveal the molecular basis of the genetic interaction, for instance, by analyzing the physical interaction between TOP1a and RBR.…”

Section: Discussionmentioning

confidence: 99%

TOPOISOMERASE1α Acts through Two Distinct Mechanisms to Regulate Stele and Columella Stem Cell Maintenance

Zhang

Zheng²,

Hong³

et al. 2016

Plant Physiol.

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ORCID IDs: 0000-0003-2848-4919 (J.M.P.-P.); 0000-0001-6194-6316 (J.X.). TOPOISOMERASE1 (TOP1), which releases DNA torsional stress generated during replication through its DNA relaxation activity, plays vital roles in animal and plant development. In Arabidopsis (Arabidopsis thaliana), TOP1 is encoded by two paralogous genes (TOP1a and TOP1b), of which TOP1a displays specific developmental functions that are critical for the maintenance of shoot and floral stem cells. Here, we show that maintenance of two different populations of root stem cells is also dependent on TOP1a-specific developmental functions, which are exerted through two distinct novel mechanisms. In the proximal root meristem, the DNA relaxation activity of TOP1a is critical to ensure genome integrity and survival of stele stem cells (SSCs). Loss of TOP1a function triggers DNA double-strand breaks in S-phase SSCs and results in their death, which can be partially reversed by the replenishment of SSCs mediated by ETHYLENE RESPONSE FACTOR115. In the quiescent center and root cap meristem, TOP1a is epistatic to RETINOBLASTOMA-RELATED (RBR) in the maintenance of undifferentiated state and the number of columella stem cells (CSCs). Loss of TOP1a function in either wild-type or RBR RNAi plants leads to differentiation of CSCs, whereas overexpression of TOP1a mimics and further enhances the effect of RBR reduction that increases the number of CSCs. Taken together, these findings provide important mechanistic insights into understanding stem cell maintenance in plants.

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Ocular Pharmacology of Topotecan and Its Activity in Retinoblastoma

Cited by 40 publications

References 58 publications

Management of advanced uni‐ or bilateral retinoblastoma with macroscopic optic nerve invasion

Management of advanced uni‐ or bilateral retinoblastoma with macroscopic optic nerve invasion

Combined high‐dose intra‐arterial and intrathecal chemotherapy for the treatment of a case of extraocular retinoblastoma

TOPOISOMERASE1α Acts through Two Distinct Mechanisms to Regulate Stele and Columella Stem Cell Maintenance

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