Recurrent Neuroblastoma in Patients Initially Classified as Intermediate Risk
(Risk categories are defined in Table 1 in the Stage Information section of the summary.)
The current standard of care is based on the experience from the COG Intermediate-Risk treatment plan (COG-A3961). Local regional recurrence of neuroblastoma with favorable biology that occurs more than 3 months after completion of 12 weeks of chemotherapy may be treated surgically. If resection is less than near total, then 12 additional weeks of chemotherapy may be given. Chemotherapy consists of moderate doses of carboplatin, cyclophosphamide, doxorubicin, and etoposide. The cumulative dose of each agent is kept low to minimize permanent injury from the chemotherapy regimen, as used in a prior COG trial (COG-A3961).
Treatment options under clinical evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- COG-ANBL0531: The COG Intermediate-Risk study treats risk/treatment Group 2 or 3 patients (previously classified as intermediate risk) who develop progressive nonmetastatic disease with surgery if possible. If surgery achieves a very good partial response (VGPR), no further therapy is given. If a VGPR is not achieved, additional cycles of chemotherapy are given to total eight cycles and additional surgery is performed if possible. For those patients that still do not reach a VGPR, six cycles of topotecan and cyclophosphamide chemotherapy are given until a VGPR is achieved. Treatment Group 4 patients have already received eight cycles of chemotherapy or have progressed on the standard chemotherapy regimen, and surgery and up to six cycles of topotecan and cyclophosphamide chemotherapy are administered until a VGPR is achieved.
If the recurrence is metastatic and/or occurs while on chemotherapy or within 3 months of completing chemotherapy and/or has unfavorable biologic properties, the prognosis is poor and the patient should be treated with an aggressive regimen of combination chemotherapy consisting of very high doses of the drugs listed above, and often also including ifosfamide and high-dose cisplatin. Both myeloablative therapy and postchemotherapy retinoic acid may improve outcome of newly diagnosed patients with a poor prognosis. These modalities are commonly employed in the treatment of patients with a recurrence that augurs a poor prognosis.
Recurrent or Refractory Neuroblastoma in Patients Initially Classified as High Risk
(Risk categories are defined in Table 1 in the Stage Information section of this summary.)
Any recurrence in patients initially classified as high risk signifies a very poor prognosis. Published data on outcome of recurrent high-risk neuroblastoma are limited. Data from three consecutive German high-risk neuroblastoma trials demonstrated that 23 patients who underwent a second autologous stem cell transplantation (SCT) had a better median survival (2.08 years) and 3-year survival rate from recurrence (43%) compared with 74 patients who had no second chemotherapy (median survival, 0.24 years; 3-year survival rate, 4%) and 135 patients who underwent second-line chemotherapy but did not undergo a second autologous SCT (median survival, 0.89 years; 3-year survival rate, 9%). This shows that intensive second-line therapy is feasible and a small subgroup of relapsed high-risk neuroblastoma patients may benefit from intensive relapse chemotherapy and a second autologous SCT.[Level of evidence: 3iiiA] Whether this intense therapy is better than other salvage regimens is unknown. Topotecan alone and in combination with cyclophosphamide or etoposide has been used in patients with recurrent disease who did not receive topotecan initially.; [Level of evidence: 1A]; [Level of evidence:3iiiDiv] High-dose carboplatin-irinotecan-temozolomide has been used in patients resistant or refractory to regimens containing topotecan. The combination of irinotecan and temozolomide had a 15% response rate in one study.[Level of evidence: 2A] Additionally, phase I or phase II clinical trials are appropriate and should be considered.