Neuroblastoma Chemotherapy Regimens

Induction Therapy for High-Risk Neuroblastoma

The National Comprehensive Cancer Network recommends the 5-cycle ANBL12P1 or ANBL1531 induction protocols, which include combinations of topotecan, cyclophosphamide, cisplatin, etoposide, and doxorubicin, followed by consolidation with tandem transplantation using high-dose chemotherapy for patients with high-risk neuroblastoma 1, 2
Induction therapy aims to reduce disease burden through multiagent cytoreductive chemotherapy combined with surgical resection of primary tumor and locoregional disease 3
Collection of autologous peripheral blood stem cells during induction is done to support later consolidation therapy 1
The ANBL12P1 or ANBL1531 regimens have a response rate of approximately 80% of patients achieving partial response or better 2
The American College of Cardiology is not mentioned in this context, however, the NCCN-preferred protocols include cycles 1-2 with topotecan and cyclophosphamide, and subsequent cycles with cisplatin-based and alkylator-intensive combinations 1, 2, 4

Tandem transplantation with two consecutive rounds of high-dose chemotherapy with autologous stem cell rescue is recommended for patients who respond adequately to induction therapy, with a significantly improved 3-year EFS (61.6% vs 48.4%) compared to single transplant 5, 6
The first transplant uses thiotepa/cyclophosphamide, and the second transplant uses reduced-dose carboplatin/etoposide/melphalan (CEM) 5
Busulfan and melphalan (BuMel) is preferred in European protocols based on superior EFS compared to CEM, but with a higher risk of sinusoidal obstruction syndrome 6

For certain subgroups with more favorable high-risk disease, single transplant may be appropriate, including stage L2, ≥18 months, unfavorable histology, MYCN non-amplified, and stage M, 12 to <18 months, MYCN non-amplified with unfavorable histology, diploid DNA, or SCAs 6
Patients with progressive disease during induction are not candidates for consolidation therapy and should receive non-myeloablative therapies 5
Patients with minor response or stable disease after induction require individualized approaches 5
Response assessment at the end of induction is critical for determining subsequent therapy, with approximately 9% of patients progressing despite intensive regimens 1, 4

The National Comprehensive Cancer Network recommends switching to alternative chemotherapy regimens, such as high-dose cyclophosphamide-based combinations or topotecan-containing regimens, for patients with high-risk neuroblastoma who have persistent bone marrow disease after two cycles of rapid COJEC and TVD, with multidisciplinary reassessment every 2 cycles to determine if adequate response has been achieved for proceeding to consolidation therapy 7
Cyclophosphamide and topotecan combinations can be used as additional treatment for patients who did not achieve target response with initial chemotherapy, as seen in the COG ANBL0531 trial, and this approach can be adapted for high-risk patients with inadequate response 7
The NCCN guidelines state that if the targeted tumor reduction goal with initial chemotherapy was not achieved, additional chemotherapy should be given with re-evaluation after every 2 cycles, with multidisciplinary discussion regarding potential risks and benefits at each timepoint 7

Evaluate disease status after every 2 cycles of alternative chemotherapy to determine whether adequate response has been achieved to proceed to consolidation, further alternative chemotherapy is warranted, or disease has progressed, requiring transition to non-myeloablative approaches 7

Surgical resection of primary tumor should be attempted between induction and consolidation phases, as recommended by the National Comprehensive Cancer Network 7

Do not continue the same failing regimen beyond 2 cycles without modification, as the guidelines explicitly recommend re-evaluation and regimen change after every 2 cycles if target response is not achieved, according to the National Comprehensive Cancer Network 7
The key distinction is that patients with minor response or stable disease after salvage chemotherapy require individualized approaches with continued reassessment, while those with progressive disease should not receive further intensive cytotoxic therapy, as stated by the National Comprehensive Cancer Network 7