2.1 Treatment details
The treatment algorithm is illustrated in Figure 1. The induction was with rapid COJEC as per the HR-NBL1/SIOPEN protocol.15The drugs in rapid COJEC included cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide. Each cycle was administered at 10 days interval, irrespective of count recovery. Granulocyte-colony stimulating factor (G-CSF) was administered prophylactically after every cycle. A reassessment was performed at the end of induction chemotherapy. As per the international neuroblastoma response criteria, the response was categorized as complete (CR), very good partial (VGPR), partial (PR), mixed (MR), no response (NR), or progressive disease (PD) at primary and metastatic sites.16 A favorable reassessment was followed by surgical resection of the primary tumor. Consolidation was with 4 cycles of TVD (Table 1). Each cycle of TVD was supported with G-CSF. The subsequent cycle was administered at 21-28 days following count recovery. TVD was administered either as in-patient or outpatient, subject to the availability of beds. Infusion of vincristine and doxorubicin was modified for ease and to enable administration in daycare. Vincristine was administered as an intravenous push on days 5 and 6 instead of continuous 48-hours infusion recommended in the SIOPEN protocol. Doxorubicin was administered as a 4-hours infusion on days 5 and 6 instead of a continuous 48-hours infusion. Consolidation chemotherapy was followed by external beam radiotherapy to the tumor bed, and differentiation therapy with six, 2-weekly cycles of isotretinoin. No further therapy was offered to patients who had a relapse or progressive disease.