Periocular Topotecan for Intraocular Retinoblastoma

Mallipatna, Ashwin; Dimaras, Helen; Chan, Helen S. L.; Hèon, Elise; Gallie, Brenda L.

doi:10.1001/archophthalmol.2011.130

Cited by 63 publications

(33 citation statements)

References 32 publications

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“…Following subconjunctival injections of 10 µg in mice, there was no toxicity on fundus examination or histopathology 24. Topotecan as a periocular injection for retinoblastoma has also been well-tolerated, with only minimal conjunctival congestion and eyelid chemosis, and negligible systemic complications 14. Rabbit eyes injected with four-weekly doses of up to 5 µg/0.1 mL of intravitreal topotecan showed no significant retinal or systemic toxicity 25.…”

Section: Discussionmentioning

confidence: 99%

“…Topotecan has been used as a systemic chemotherapy for resistant intraocular retinoblastoma and systemic metastasis 13. As a periocular injection, topotecan has been used in patients with recurrent tumour and in those not amenable to systemic chemotherapy 14. Intravitreal topotecan injection in combination with melphalan has been reported to achieve complete vitreous seed regression with no change observed on electroretinogram (ERG) 16.…”

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confidence: 99%

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Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

et al. 2017

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

et al. 2017

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“…These last modalities were developed during the study period. [13][14][15] The current conservative strategy often needs the combination of several of the therapeutic modalities indicated above. Our team published, in 2008, a phase II prospective study on the efficacy of a treatment combining local therapies or chemothermotherapy after chemoreduction by etoposide and carboplatin (2 cycles) whenever the tumors are not directly treatable by local treatments.…”

Section: Introductionmentioning

confidence: 99%

Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy

Rouic

Aerts

Hajage

et al. 2015

Eye

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Purpose Intraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible longterm toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristinecarboplatin vs etoposide-carboplatin. Patients and methods The study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin-carboplatin (new arm) vs etoposide-carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years. Results A total of 65 eyes in 55 children were included in the study (May 2004 to August 2009. Of these, 32 eyes (27 children) were treated in the arm etoposide-carboplatin and 33 eyes (28 children) in the arm vincristin-carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin-carboplatin and 26/32 (81.2%) in the arm etoposide-carboplatin. Conclusion Even if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine-carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposidecarboplatin combination.

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“…5 Despite a different initiating mechanism and cell of origin, our data indicate histologic and (post-RB1 loss) molecular similarities between TAg-RB and human retinoblastoma. These similarities, plus the recent successful translation of therapies tested in TAg-RB to the clinic, 6,7 validate TAg-RB as a useful model. After more than 30 years of research, the identity of the retinoblastoma cell of origin remains complex and invites discussion; but most of all, it requires far more research in both mouse models and human disease.…”

Section: Madhavan and Khetanmentioning

confidence: 85%

Author Response: Does the Time of Inactivation of pRb Determine the Cell of Origin of Retinoblastoma?

Corson

Pajovic

Dimaras

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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raise questions about our paper that were largely addressed in the original publication.2 First, we reiterate that it is not possible to draw direct conclusions about the cell of origin of human retinoblastoma on the basis of data in the TAg-RB mouse model; unfortunately, we lack the unambiguous marker of the tumor lineage in human retinoblastoma that TAg provides in the mouse. Second, the timing of RB1 loss in humans does not coincide with the developmental period in which TAg is activated in TAg-RB. Human retinoblastoma tumors have frequently been detected prenatally. TAg-RB arises from the inner nuclear layer after postnatal day 8, 2 and so it is unlikely to display a cone phenotype, as Madhavan and Khetan postulate, since the cones have already matured by that point. 4 Moreover, we have never observed overlap between TAg and cone opsin or RXR␥ staining (Pajovic S, unpublished data, 2010), but have shown overlap with multiple cell markers that clearly demonstrated that the cell of origin in this model possesses features of differentiated Müller glia with progenitor properties.2 Although timing of pRB inactivation in our model makes it "not surprising that the cells stain for maturing progenitors," what is interesting is that inactivation of pRB at this time and in this unique cell type produces a tumor with significant similarity to human retinoblastoma, regardless of whether it originates from the same cell type.We agree with Madhavan and Khetan 1 that the genetic changes after Rb1 loss should be evaluated in other mouse models of retinoblastoma, and we would welcome such studies. Indeed, we regard our original paper as an invitation to our colleagues to molecularly and histologically define other mouse models and to interpret mouse data with caution in regard to human retinoblastoma. However, the assertion that the TAg-RB model cannot be considered to be a "good" model for human disease without such studies 1 is flawed. It has been said that there are no good models, only useful ones.5 Despite a different initiating mechanism and cell of origin, our data indicate histologic and (post-RB1 loss) molecular similarities between TAg-RB and human retinoblastoma. These similarities, plus the recent successful translation of therapies tested in TAg-RB to the clinic, 6,7 validate TAg-RB as a useful model. After more than 30 years of research, the identity of the retinoblastoma cell of origin remains complex and invites discussion; but most of all, it requires far more research in both mouse models and human disease.

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Periocular Topotecan for Intraocular Retinoblastoma

Cited by 63 publications

References 32 publications

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy

Author Response: Does the Time of Inactivation of pRb Determine the Cell of Origin of Retinoblastoma?

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