Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients

Abstract

Background Evaluate the efficacy of two courses of vincristine and topotecan (VT) neoadjuvant intravenous chemotherapy in reducing retinoblastoma tumor volumes. Methods Twenty‐seven patients with previously untreated, bilateral advanced retinoblastoma who were enrolled on a prospective treatment protocol (NCT00186888). Patients underwent high‐resolution ophthalmic imaging at diagnosis and were reimaged following treatment with two cycles of VT. Tumor height and diameter were measured before and after treatment, and tumor volumes were calculated. Statistical methods for dependent samples were used. Results Imaging was completed for 75 tumors in 23 patients (43 eyes). After two cycles of VT, median decrease in tumor height was 47% and median decrease in tumor diameter was 22%. Median decrease in estimated tumor volume was 74%. Sixty‐one of 75 tumors demonstrated >50% reduction in tumor volume. Distance from the optic nerve (=0 vs >0), age (<4 vs >4 months), macular location (within vs outside), and time (pre‐ and posttreatment) were found significantly associated with log‐transformed tumor volume adjusting for the repeated effect of patient eye using generalized estimating equations to estimate the parameters of a generalized linear model (P < .0001 [β: 1.95, CI: 1.53‐2.36], P = .0031 [β: 1.49, CI: 0.57‐2.41], P < .0001 [β: .94, CI: 0.54‐1.35], and P < .0001 [β: 1.43, CI: 1.15‐1.71]). Conclusion Chemoreduction was achieved in all patients and most retinoblastoma tumors following two cycles of VT. Reduction in tumor dimensions was comparable to that reported with platinum‐based chemotherapy. Tumor location, distance from the optic nerve, and age at diagnosis were significant predictors of treatment response.

Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles

“…VINC uptake by has been described as carrier-mediated transport and its mechanism of action is microtubule depolymerization leading to cell-cycle arrest [ 54 , 55 ]. VINC has been studied in combination with other therapeutic drugs for RB treatment in clinical trials [ 56 , 57 ] and has been associated with colorectal cancer and neurotoxicity [ 58 , 59 ]. ETOP diffuses across the cell membrane and functions by inhibiting topoisomerase II, leading to DNA damage and apoptotic cell death [ 60 , 61 ].…”

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

“…This combination is most suitable for the treatment of retinoblastoma. In patients with this diagnosis, it enables chemoreduction and is well effective already after two cycles [ 106 ]. In addition to retinoblastoma, also neuroblastoma might be potentially treatable with vincristine and topotecan co-administered with doxorubicin.…”