Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma

Taich, Paula Juliana; Ceciliano, Alejandro; Buitrago, Emiliano; Sampor, Claudia; Fandiño, Adriana; Villasante, Francisco; Lucena, Evandro; Romero, Livia; Chantada, Guillermo; Schaiquevich, Paula

doi:10.1016/j.ophtha.2013.10.045

Cited by 48 publications

(37 citation statements)

References 22 publications

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“…A few translational studies have resulted in changes in retinoblastoma clinical practice. 203 Innovative delivery systems to target small-volume subretinal tumours and vitreous seeding include episcleral implants 204 and nanoparticles 205 . Approaches adjusting chemotherapy schedules and dose intensity (metronomic therapy) 206 may particularly play an important role in palliative care for retinoblastoma.…”

Section: Discussionmentioning

confidence: 99%

Retinoblastoma

Dimaras

Corson

Cobrinik

et al. 2015

Nat Rev Dis Primers

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424

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Retinoblastoma is a rare cancer of the infant retina, which forms when both RB1 alleles mutate in a susceptible retinal cell, likely a cone photoreceptor precursor. Loss of the tumour suppressor functions of the retinoblastoma protein, pRB, leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in virtually all tissues, cone precursors have biochemical and molecular features that may sensitize to RB1 loss to enable tumourigenesis. Retinoblastoma is diagnosed in ~8,000 children each year worldwide. Patient survival is >95% in high-income countries, but <30% globally. However, outcomes are improving through increasing awareness for earlier diagnosis, new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted since survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma as well as second cancers in patients with germline RB1 mutations.

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Section: Discussionmentioning

confidence: 99%

Retinoblastoma

Dimaras

Corson

Cobrinik

et al. 2015

Nat Rev Dis Primers

Self Cite

424

390

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“…Other researchers showed synergistic activity of combination melphalan and topotecan IAC and cyclophosphamide in their pharmacokinetic study 116,117. The combination of melphalan and topotecan for IAC of retinoblastoma was effective and well tolerated without increased hematologic toxicity with respect to melphalan administered as a single drug 117,118.…”

Section: Clinical Management Of Retinoblastomamentioning

confidence: 95%

“…The combination of melphalan and topotecan for IAC of retinoblastoma was effective and well tolerated without increased hematologic toxicity with respect to melphalan administered as a single drug 117,118. Topotecan showed a preferential passage to the vitreous humor, where it stayed for at least 4 hours more than its calculated IC 50 (50% inhibitory concentration) 119…”

Section: Clinical Management Of Retinoblastomamentioning

confidence: 99%

Risk definition and management strategies in retinoblastoma: current perspectives

Ghassemi

Khodabande

2015

OPTH

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This manuscript focuses on high-risk factors of metastatic disease in retinoblastoma and evaluation of the current treatments of retinoblastoma. Presence of histopathologic high-risk factors is associated with a higher risk of local recurrence and systemic metastasis. Currently, globe-sparing therapies, including systemic chemotherapy, intra-arterial chemoreduction, intravitreal chemotherapy, focal consolidation, and combination therapies, are being used and investigated actively. Major advances are being made in the diagnosis and management of retinoblastoma that will lead to improved morbidity and mortality rates in patients with retinoblastoma. By saving the globes, fronting with some high-risk factors for metastasis would be inevitable. International multi-institutional prospective studies could resolve current uncertainties regarding the main tumor treatment regimens for each patient and indications for chemoprophylaxis for high-risk-factor-bearing retinoblastoma cases.

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“…A two-drug IAC regimen was explored by Francis et al [52], and a three-drug regiment by Marr et al [53]. Taich et al [54] evaluated the pharmacokinetics of combination melphalan and topotecan IAC and noted synergistic activity and without increasing toxicity, compared with single-agent melphalan. Success with IAC requires skill and experience.…”

Section: When To Use Intra-arterial Chemotherapymentioning

confidence: 99%