PURPOSE

To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan.

PARTICIPANTS

A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC).

DESIGN

Retrospective cohort study.

METHODS

Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest.

MAIN OUTCOME MEASURES

Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation.

RESULTS

There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity.

CONCLUSIONS

Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.