BACKGROUND: We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series.

PROCEDURE: Fifteen patients with bone marrow (n = 14), bone (n = 10), orbit (n = 9), and/or liver (n = 4) disease were treated. Induction chemotherapy usually consisted of vincristine, cyclophosphamide, cisplatin, and etoposide. The high-dose chemotherapy regimen included carboplatin and thiotepa alone (n = 1) or with etoposide (n = 5) or topotecan (n = 7).

RESULTS: Bone marrow cleared at first post-initiation of chemotherapy examination in all patients and stem cells were harvested after a median of 3.5 cycles of chemotherapy (range 3-6 cycles). Two patients progressed prior to high-dose chemotherapy and died. Thirteen received high-dose chemotherapy at a median of 6 months post-diagnosis of metastases (range 4-8 months). Ten are retinoblastoma-free in first remission at a median follow-up of 103 months (range 34-202 months) while three recurred (two in the CNS, one in the mandible) 14-20 months post-diagnosis of metastases. Retinoblastoma-free and event-free survival at 5 years are 67% (95% confidence interval 38-85%) and 59% (95% confidence interval 31-79%). Six of the 10 survivors received radiation therapy. Three patients developed secondary osteosarcoma 14, 4, and 9 years after diagnosis of metastatic disease.

CONCLUSIONS: Intensive multimodality therapy including high-dose chemotherapy with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma treated. The contribution of external beam radiation therapy is unclear.