Correspondence

Case 36-2009: A Man with Cough, Hoarseness, and Abnormalities on Chest Imaging

N Engl J Med 2010; 362:961March 11, 2010

Article

To the Editor:

In the Case Record (Nov. 19 issue),1 Choy and colleagues note the interest stemming from phase 1 trials involving the type I insulin-like growth factor receptor (IGF-IR) as a targeted therapy in Ewing's sarcoma. However, the responses to such therapy were seen in a highly selected subgroup of patients with Ewing's sarcoma. This approach is the subject of extensive research, given that there are more than 25 different anti–IGF-IR molecules (either monoclonal antibodies or small-molecule inhibitors) in different stages of development.2 In addition to the regimens in patients with relapse that are mentioned in the Clinicopathological Conference, other internationally accepted second-line salvage options with the use of commercially available agents in patients with Ewing's sarcoma include temozolomide with irinotecan, topotecan with cyclophosphamide, and high-dose ifosfamide.3 Another drug used in bone sarcomas is zoledronic acid, with its pleiotropic effects as an analgesic in palliating bone pain4 and in vitro activity against Ewing's sarcoma cell lines5; the Euro-Ewing 2008 study, which involves the administration of adjuvant zoledronic acid or placebo to a low-risk subgroup of patients with Ewing's sarcoma, is under way (ClinicalTrials.gov number, NCT00987636).

Vivek Subbiah, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX
viveksubbiah@gmail.com

No potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 36-2009). N Engl J Med 2009;361:2080-2087
   Full Text | Web of Science | Medline

2. 2

   Rodon J, DeSantos V, Ferry RJ Jr, Kurzrock R. Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials. Mol Cancer Ther 2008;7:2575-2588
   CrossRef | Web of Science | Medline

3. 3

   Subbiah V, Anderson P, Lazar AJ, Burdett E, Raymond K, Ludwig JA. Ewing's sarcoma: standard and experimental treatment options. Curr Treat Options Oncol 2009;10:126-140
   CrossRef | Medline

4. 4

   Body JJ. Breast cancer: bisphosphonate therapy for metastatic bone disease. Clin Cancer Res 2006;12:6258s-6263s
   CrossRef | Web of Science | Medline

5. 5

   Zhou Z, Guan H, Duan X, Kleinerman ES. Zoledronic acid inhibits primary bone tumor growth in Ewing sarcoma. Cancer 2005;104:1713-1720
   CrossRef | Web of Science | Medline

Author/Editor Response

Subbiah raises an interesting question of how best to treat patients with Ewing's sarcoma that is refractory to primary chemotherapy and appropriately points out two commercially available regimens for recurrent Ewing's sarcoma that combine a topoisomerase I inhibitor with an alkylating agent. Combination therapy with irinotecan and temozolomide has been shown in retrospective studies to yield overall objective response rates of 50 to 63%.1,2 Similarly, combination therapy with topotecan and cyclophosphamide has been shown to yield a 33% partial response rate.3 Based on these studies, both regimens have been used as reasonable second-line or third-line treatment options for recurrent Ewing's sarcoma.

However, although the above studies cumulatively involved 19 patients with disease that is refractory to the primary treatment regimen (as was the case with the patient described in the Case Record), none of these patients showed an objective response to the studied regimens. Therefore, in such patients, commercial agents are likely to have very modest benefits, and, whenever possible, treatment in a clinical trial would be the preferred approach.

Edwin Choy, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 02114

Since publication of his article, the author reports no further potential conflict of interest.

3 References

1. 1

   Wagner LM, McAllister N, Goldsby R, et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer 2007;48:132-139
   CrossRef | Web of Science | Medline

2. 2

   Casey DA, Wexler LH, Merchant MS, et al. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer 2009;53:1029-1034
   CrossRef | Web of Science | Medline

3. 3

   Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jurgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer 2006;47:795-800
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Vivek Subbiah, Pete Anderson. (2011) Targeted Therapy of Ewing's Sarcoma. Sarcoma 2011, 1-10
   CrossRef