Current Clinical Trials

Although patients with recurrent or progressive rhabdomyosarcoma sometimes achieve complete remission with secondary therapy, the long-term prognosis is usually poor.[1,2] The prognosis is most favorable (50% to 70% 5-year survival rates) for children who initially present with stage I or Group I disease and embryonal histology, and who have smaller tumors or present with a local or regional recurrence.[1-3] The small number of children with botryoid histology who relapse have a similarly favorable prognosis.[1] Most other children who relapse have an extremely poor prognosis.[1] A retrospective review of rhabdomyosarcoma patients from German soft tissue sarcoma trials identified time to recurrence as an important independent prognostic factor. Shorter time to recurrence was associated with higher risk of mortality from recurrent rhabdomyosarcoma.[4][Level of evidence: 3iiB]

The selection of further treatment depends on many factors, including the site(s) of recurrence, previous treatment, and individual patient considerations. Treatment for local or regional recurrence may include wide local excision or aggressive surgical removal of tumor, particularly in the absence of widespread bony metastases.[5] Some survivors have also been reported after surgical removal of only one or a few metastases in the lung.[5] RT should be considered for patients who have not already received RT in the area of recurrence, or rarely for those who have received RT but for whom surgical excision is not possible. Previously unused, active, single agents or combinations of drugs may also enhance the likelihood of disease control.

The following standard chemotherapy regimens have been used to treat recurrent rhabdomyosarcoma:

• Carboplatin/etoposide.[6]
• Ifosfamide, carboplatin, and etoposide.[7,8]
• Cyclophosphamide/topotecan.[9]
• Irinotecan with or without vincristine.[10-13]

Treatment options under clinical evaluation for recurrent rhabdomyosarcoma:

• On the basis of historical relapse data from the Intergroup Rhabdomyosarcoma Study Group,[1] the Children’s Oncology Group is currently analyzing a risk-based approach to salvage treatment for rhabdomyosarcoma patients experiencing a first relapse or progressive disease. Relapsed patients with a favorable prognosis received doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide. For patients with a poor prognosis and measurable disease, a randomized study of two administration schedules of irinotecan (five daily doses for 1 week vs. five daily doses for 2 weeks) in combination with vincristine preceded treatment with doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide. Poor-prognosis patients without measurable disease received doxorubicin/cyclophosphamide with the addition of an investigational agent, tirapazamine, alternating with ifosfamide/etoposide.
• Intensive chemotherapy followed by autologous bone marrow transplantation. Very intensive chemotherapy followed by autologous bone marrow reinfusion is also under investigation for patients with recurrent rhabdomyosarcoma. A review of the published data did not determine a significant benefit for patients who underwent this salvage treatment approach.[14]
• Single-agent vinorelbine.[15]
• Combination vinorelbine and low-dose cyclophosphamide.[16]
• Rapamycin.[17]
• Topotecan, vincristine, and doxorubicin.[18][Level of evidence: 3iiiDiii]
• New agents under clinical evaluation in phase I and phase II trials should be considered for relapsed patients.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Pappo AS, Anderson JR, Crist WM, et al.: Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group. J Clin Oncol 17 (11): 3487-93, 1999.  [PUBMED Abstract]
   
   
2. Mazzoleni S, Bisogno G, Garaventa A, et al.: Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma. Cancer 104 (1): 183-90, 2005.  [PUBMED Abstract]
   
   
3. Dantonello TM, Int-Veen C, Winkler P, et al.: Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma. J Clin Oncol 26 (3): 406-13, 2008.  [PUBMED Abstract]
   
   
4. Mattke AC, Bailey EJ, Schuck A, et al.: Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas? Pediatr Blood Cancer 52 (7): 772-6, 2009.  [PUBMED Abstract]
   
   
5. Hayes-Jordan A, Doherty DK, West SD, et al.: Outcome after surgical resection of recurrent rhabdomyosarcoma. J Pediatr Surg 41 (4): 633-8; discussion 633-8, 2006.  [PUBMED Abstract]
   
   
6. Klingebiel T, Pertl U, Hess CF, et al.: Treatment of children with relapsed soft tissue sarcoma: report of the German CESS/CWS REZ 91 trial. Med Pediatr Oncol 30 (5): 269-75, 1998.  [PUBMED Abstract]
   
   
7. Kung FH, Desai SJ, Dickerman JD, et al.: Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of childhood: a Pediatric Oncology Group Phase I/II study. J Pediatr Hematol Oncol 17 (3): 265-9, 1995.  [PUBMED Abstract]
   
   
8. Van Winkle P, Angiolillo A, Krailo M, et al.: Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer 44 (4): 338-47, 2005.  [PUBMED Abstract]
   
   
9. Saylors RL 3rd, Stine KC, Sullivan J, et al.: Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol 19 (15): 3463-9, 2001.  [PUBMED Abstract]
   
   
10. Cosetti M, Wexler LH, Calleja E, et al.: Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol 24 (2): 101-5, 2002.  [PUBMED Abstract]
    
    
11. Pappo AS, Lyden E, Breitfeld P, et al.: Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. J Clin Oncol 25 (4): 362-9, 2007.  [PUBMED Abstract]
    
    
12. Vassal G, Couanet D, Stockdale E, et al.: Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: a joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. J Clin Oncol 25 (4): 356-61, 2007.  [PUBMED Abstract]
    
    
13. Furman WL, Stewart CF, Poquette CA, et al.: Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children. J Clin Oncol 17 (6): 1815-24, 1999.  [PUBMED Abstract]
    
    
14. Weigel BJ, Breitfeld PP, Hawkins D, et al.: Role of high-dose chemotherapy with hematopoietic stem cell rescue in the treatment of metastatic or recurrent rhabdomyosarcoma. J Pediatr Hematol Oncol 23 (5): 272-6, 2001 Jun-Jul.  [PUBMED Abstract]
    
    
15. Casanova M, Ferrari A, Spreafico F, et al.: Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma. Cancer 94 (12): 3263-8, 2002.  [PUBMED Abstract]
    
    
16. Casanova M, Ferrari A, Bisogno G, et al.: Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. Cancer 101 (7): 1664-71, 2004.  [PUBMED Abstract]
    
    
17. Houghton PJ, Morton CL, Kolb EA, et al.: Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer 50 (4): 799-805, 2008.  [PUBMED Abstract]
    
    
18. Meazza C, Casanova M, Zaffignani E, et al.: Efficacy of topotecan plus vincristine and doxorubicin in children with recurrent/refractory rhabdomyosarcoma. Med Oncol 26 (1): 67-72, 2009.  [PUBMED Abstract]
    
    

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