Topotecan-based regimen allows ocular salvage in advanced intraocular retinoblastoma

By Will Boggs MD

NEW YORK (Reuters Health) - Topotecan combined with vincristine, carboplatin, and aggressive focal therapies allows ocular salvage in patients with advanced intraocular retinoblastoma, researchers report.

"As we have an excellent survival rate, we have shifted the focus of therapy and the focus of discussion with parents at diagnosis to focus on saving eyes," said Dr. Rachel C. Brennan from St. Jude Children's Research Hospital and the University of Tennessee Health Science Center in Memphis.

"However, I think this paper shows that not only are we saving eyes, but also we have been able to save eyes with vision," she told Reuters Health by email.

Systemic chemotherapy with vincristine, carboplatin, and etoposide is commonly used to treat retinoblastoma, the most common intraocular tumor of childhood. In preclinical studies, topotecan enhanced the effectiveness of carboplatin in retinoblastoma cell lines and xenografts, Dr. Brennan and colleagues note in a paper online October 10 in the Journal of Clinical Oncology.

The team assessed the efficacy of systemic topotecan when combined with vincristine and carboplatin in 27 children (median age, 8.4 months) with bilateral retinoblastoma.

Twenty-four patients (89%) completed all courses of prescribed chemotherapy, and all eyes received focal therapy. Two patients who developed progressive disease before the third course of chemotherapy required external beam radiation therapy and, eventually, nucleation.

The 10-year event-free survival and ocular survival per patient were both 69.2%, and the rates per eye were both 82.4%, the researchers found.

Event-free and ocular survival were greater for patients with Reese-Ellsworth group I to III eyes (100%) than for group IV to V eyes (78%).

Ten eyes were enucleated: one at diagnosis, one because of neovascular glaucoma after therapy, one with hemorrhage related to tumor response during therapy, three that developed progressive disease during therapy, and four that developed progressive disease after therapy.

No patient required additional treatment after enucleation, and there were no reports of metastatic disease or secondary malignancies. At last follow-up (median, 7.4 years), all patients were alive.

All patients experienced neutropenia, and two-thirds experienced fever and neutropenia. There were no sight-threatening toxicities.

At a median age of 8 years (range, 5 to 11 years), 29 of 48 eyes had measurable vision, six eyes could count fingers, three eyes could perceive hand motion, and two eyes had light perception only. Twenty patients (83%) had one eye with documented vision of 20/70 or better, and 18 patients (75%) had at least 20/40 vision in one eye.

"These results, while very promising, are part of a single institution prospective trial," Dr. Brennan said. "It is important to move this drug forward within the context of a large cooperative group (COG) clinical trial. But I am hopeful that topotecan will be used more often in upfront therapy for patients with advanced intraocular retinoblastoma."

"The conversation about treatment for retinoblastoma should be a partnership between pediatric oncology and pediatric ophthalmology/ocular oncology," she said. "Novel methods for delivering therapy (locally delivered therapy) should be carefully monitored to ensure the outcomes are truly relevant in terms of not only globe salvage, but preservation of vision and decreased late effects in this vulnerable population."

Dr. Brennan added, "I have also been impressed with the families of our patients, who refuse to declare their children 'limited' and help to push them to reach their full potential. They are a critical component of our team, and I am grateful to them!"

Dr. Pia Mendoza from Emory University School of Medicine, Atlanta, Georgia, who recently reviewed the therapeutic options for retinoblastoma, told Reuters Health by email, "The use of topotecan as part of the chemotherapy regimen for the treatment of advanced intraocular retinoblastoma seems promising. The regimen combined with focal therapies was effective in controlling tumor and resulted in not just ocular salvage, but also preservation of functional vision in these patients."

"In the past, enucleation and external beam radiation were mainstays in the management of advanced retinoblastoma," she explained. "Side effects of radiation led to blindness, bony disfigurement, and second malignancies. In recent years, we have shifted away from radiation and toward chemotherapy and focal therapy to allow for globe salvage."

"Translational research and clinical trials like these are important for understanding this rare but debilitating childhood cancer," said Dr. Mendoza, who was not involved in the new study. "Local routes of chemotherapy administration (intra-arterial and intravitreal delivery) are currently being incorporated into treatment algorithms for retinoblastoma. Additional studies on the use of intra-arterial or intravitreal topotecan with long-term follow-up are needed."

The study did not have commercial funding.

SOURCE: https://jco.ascopubs.org/content/early/2016/10/06/JCO.2016.69.2996.abstract

J Clin Oncol 2016.