Topotecan and cyclophosphamide are both active drugs in neuroblastoma and various combinations of these two drugs with or without other additional drugs have been used in a number of phase II trials. There are no FDA approved drugs for neuroblastoma and therefore this regimen and the individual drugs are considered off-label and experimental but it is medically necessary based on phase II studies, one phase III study and the lack of alternatives. Phase III studies are difficult to perform in this disease because of the wide use of bone marrow transplatation. Topotecan and Cytoxan are not NCCN Compendia and NCCN guidelines recognized and I was unable to check Uptodate since I do not ahve a subscription to this proprietary database. A recent comparative phase III study found that “There is a trend toward better results with T+C than T. Incorporation of the combination into front line treatment plans deserves further exploration. ”
Saylors, Robert L., III, Stine, Kimo C., Sullivan, Jim, Kepner, James L., Wall, Donna A., Bernstein, Mark L., Harris, Michael B., Hayashi, Robert, Vietti, Teresa J.
Cyclophosphamide Plus Topotecan in Children With Recurrent or Refractory Solid Tumors: A Pediatric Oncology Group Phase II Study
J Clin Oncol 2001 19: 3463-3469
Thorsten Simon et al, Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial Journal Journal of Cancer Research and Clinical Oncology Volume 133, Number 9 / September, 2007
Frantz, C. N., London, W. B., Diller, L., Seeger, R., Sawyer, K.
Recurrent neuroblastoma: Randomized treatment with topotecan + cyclophosphamide (T+C) vs. topotecan alone(T). A POG/CCG Intergroup Study
J Clin Oncol (Meeting Abstracts) 2004 22: 8512
Publisher Springer Berlin Heidelberg
ISBN 978-3-540-40841-3 (Print) 978-3-540-26616-7 (Online) , p. 199