title: Ocular Salvage and Vision Preservation Using a Topotecan-Based Regimen for Advanced Intraocular Retinoblastoma.
abstract: Purpose To evaluate topotecan-based therapy for advanced intraocular retinoblastoma. Patients and Methods Twenty-seven patients with bilateral retinoblastoma (male patients, n = 14; median age, 8.4 months) received chemotherapy: two courses of topotecan plus vincristine followed by three alternating administrations of carboplatin and vincristine for two courses and topotecan plus vincristine for one course, with optional periocular carboplatin. Focal therapy was applied after cycle 2. Event-free survival was defined as avoidance of external-beam radiotherapy (EBRT) and enucleation. Results Of 54 eyes, 42 were Reese-Ellsworth group IV to V, and 37 were International Classification of Retinoblastoma group C to E. Eleven eyes were enucleated: one at diagnosis, nine with progressive disease including three eyes treated with EBRT, and one that developed neovascular glaucoma after completion of therapy. One patient was removed from protocol with prolonged infection in course 1; 26 patients (51 eyes) were analyzed. At 10 years, cumulative incidence of EBRT was 5.9% (SE ± 3), and event-free survival was 69.2% (SE ± 27.2). Ocular survival for Reese-Ellsworth group IV to V eyes was 77.5% (SE ± 21.2); it was 74.3% (SE ≥ 18.8) for International Classification group C to E eyes. Vision testing (median age, 7 years; range, 5 to 10 years) documented 20/70 vision or better in one eye of 23 patients; 19 (76%) of 25 patients demonstrated 20/40 vision or better in one eye. All patients experienced thrombocytopenia (41 episodes in 275 courses; 15%). There were 29 episodes of febrile neutropenia (10%). Grade 3 diarrhea was present in nine of 27 patients, and one patient had an allergic reaction to carboplatin. All patients are alive at median follow-up 7.4 years (range, 2.7 to 10 years). Conclusion Topotecan combined with vincristine, carboplatin, and aggressive focal therapies is an effective regimen for the treatment of advanced retinoblastoma and results in globe salvage with vision. Toxicities were anticipated and managed with appropriate supportive care.
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Brennan
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Qaddoumi
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Mao
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Hoehn
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.affiliation: Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Carlos Rodriguez-Galindo, and Matthew W. Wilson, St Jude Children's Research Hospital; and Rachel C. Brennan, Ibrahim Qaddoumi, Clinton F. Stewart, Mary Ellen Hoehn, and Matthew W. Wilson, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Wilson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D015353:Eye Enucleation; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D008297:Male; D011878:Radiotherapy; D012175:Retinoblastoma / Q000150:complications / Q000628:therapy*; D016879:Salvage Therapy; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage; D014786:Vision Disorders / Q000209:etiology* / Q000517:prevention & control; D014792:Visual Acuity
chemical_list: D014750:Vincristine; D019772:Topotecan; D016190:Carboplatin