Bhavna Chawla1, Fahmi Hasan2, Rachna Seth3, Sushmita Pathy4, Rajesh Pattebahadur2, Sanjay Sharma5, Ashish Upadhyaya6, Rajvardhan Azad2. 1. Ocular Oncology Service, All India Institute of Medical Sciences, New Delhi, India; Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Electronic address: bhavna2424@hotmail.com. 2. Ocular Oncology Service, All India Institute of Medical Sciences, New Delhi, India; Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. 3. Pediatric Oncology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 4. Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India. 5. Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. 6. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Abstract
PURPOSE: To compare the efficacy of 2 chemotherapeutic drug combinations as part of multimodal therapy for orbital retinoblastoma. DESIGN: Prospective, comparative, study. PARTICIPANTS: Patients with stageIII retinoblastoma (International Retinoblastoma Staging System). METHODS: Demographic and clinical features were recorded at presentation. Treatment consisted of a multimodal protocol with neoadjuvant chemotherapy, enucleation, orbital external-beam radiotherapy, and adjuvant chemotherapy. For chemotherapy, patients were randomized into 2 groups: group A patients were treated with vincristine, etoposide, and carboplatin (VEC) and group B patients were treated with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Treatment outcomes and adverse effects were recorded. Efficacy parameters were compared between the groups. MAIN OUTCOME MEASURES: Survival probability, cause of death, and chemotherapy-related toxicity. RESULTS: A total of 54 children were recruited (27 in each group). The mean ± SD follow-up was 21.3±11.34 months. The overall Kaplan-Meier survival probability was 80% (95% confidence interval [CI], 0.67-0.89) and 42% (95% CI, 0.24-0.59) at 1 year and 4 years, respectively. There were 9 deaths in group A and 15 deaths in group B. The Kaplan-Meier survival probability at 1 year was similar between the groups: 81% (95% CI, 0.60-0.91) and 79% (95% CI, 0.58-0.9) for groups A and B, respectively. At 4 years, the survival probability for group A was higher (63% [95% CI, 0.41-0.79] vs. 25% [95% CI, 0.08-0.46] for groups A and B, respectively), with a strong trend of better survival in group A over time (P = 0.05). The major cause of death was central nervous system relapse (8 patients in group A and 7 patients in group B). Two patients in group B died of sepsis after febrile neutropenia. Grade 3 and grade 4 hematologic toxicities were more common in group B, with a significant difference in grade 4 neutropenia (P = 0.002). CONCLUSIONS: This study compared the outcomes of VEC chemotherapy with a 5-drug combination of etoposide and carboplatin, alternating with cyclophosphamide, idarubicin, and vincristine, for stage III retinoblastoma. The VEC combination was found to be more effective and may be recommended as neoadjuvant and adjuvant chemotherapy.
RCT Entities:
PURPOSE: To compare the efficacy of 2 chemotherapeutic drug combinations as part of multimodal therapy for orbital retinoblastoma. DESIGN: Prospective, comparative, study. PARTICIPANTS: Patients with stage III retinoblastoma (International Retinoblastoma Staging System). METHODS: Demographic and clinical features were recorded at presentation. Treatment consisted of a multimodal protocol with neoadjuvant chemotherapy, enucleation, orbital external-beam radiotherapy, and adjuvant chemotherapy. For chemotherapy, patients were randomized into 2 groups: group A patients were treated with vincristine, etoposide, and carboplatin (VEC) and group B patients were treated with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Treatment outcomes and adverse effects were recorded. Efficacy parameters were compared between the groups. MAIN OUTCOME MEASURES: Survival probability, cause of death, and chemotherapy-related toxicity. RESULTS: A total of 54 children were recruited (27 in each group). The mean ± SD follow-up was 21.3±11.34 months. The overall Kaplan-Meier survival probability was 80% (95% confidence interval [CI], 0.67-0.89) and 42% (95% CI, 0.24-0.59) at 1 year and 4 years, respectively. There were 9 deaths in group A and 15 deaths in group B. The Kaplan-Meier survival probability at 1 year was similar between the groups: 81% (95% CI, 0.60-0.91) and 79% (95% CI, 0.58-0.9) for groups A and B, respectively. At 4 years, the survival probability for group A was higher (63% [95% CI, 0.41-0.79] vs. 25% [95% CI, 0.08-0.46] for groups A and B, respectively), with a strong trend of better survival in group A over time (P = 0.05). The major cause of death was central nervous system relapse (8 patients in group A and 7 patients in group B). Two patients in group B died of sepsis after febrile neutropenia. Grade 3 and grade 4 hematologic toxicities were more common in group B, with a significant difference in grade 4 neutropenia (P = 0.002). CONCLUSIONS: This study compared the outcomes of VEC chemotherapy with a 5-drug combination of etoposide and carboplatin, alternating with cyclophosphamide, idarubicin, and vincristine, for stage III retinoblastoma. The VEC combination was found to be more effective and may be recommended as neoadjuvant and adjuvant chemotherapy.
Authors: Laura Asnaghi; David T White; Nolan Key; Joshua Choi; Alka Mahale; Hind Alkatan; Deepak P Edward; Sahar M Elkhamary; Saleh Al-Mesfer; Azza Maktabi; Christopher G Hurtado; Grace Y Lee; Angel M Carcaboso; Jeff S Mumm; Leen Abu Safieh; Charles G Eberhart Journal: Oncogene Date: 2018-11-06 Impact factor: 9.867