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. 2003 Mar;7(1):9–11. doi: 10.1080/1357714031000114156

Phase II Study of Ifosfamide+Doxorubicin in Patients With Advanced Synovial Sarcomas (E1793): A Trial of the Eastern Cooperative Oncology Group

John H Edmonson 1,✉, Louise M Ryan 2, Carla I Falkson 3, David G Hicks 4, Ronald H Blum 5
PMCID: PMC2395511  PMID: 18521363

Abstract

Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamide+doxorubicin (88%) than from doxorubicin alone (20%) (P = 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study.

Patients Between 1994 and 1999, twelve adult patients with advanced synovial sarcomas were enrolled to receive, as their initial chemotherapy, ifosfamide 7.5 gm/m2 plus doxorubicin 60 mg/m2, given intravenously over two consecutive days every 3 weeks.

Methods Each day for 2 days doxorubicin 30 mg/m2 was infused over 5 min through a running i.v., followed by ifosfamide 3750 mg/m2 over 4 h. Continuous i.v. fluid was infused at 300 mL/h for 3 h on day 1, before chemotherapy was begun; then the infusion was continued at 100 mL/h for a total of 3 days. Mesna 750 mg/m2 was given 15 min before ifosfamide and at 4 and 8 h after ifosfamide on days 1 and 2 of each treatment cycle. Filgrastim (G-CSF) 5 μg/kg was given subcutaneously each day for 14 days beginning on day 3 of each treatment cycle to limit the severity of neutropenia.

Results Five of our 12 patients (42%) experienced partial regression of their advanced synovial sarcomas; however, this first stage result was borderline for proceeding to the second planned stage of accrual and our case accrual was quite poor. Thus, the study was closed after stage one accrual. Our patients received a median of four cycles of chemotherapy (range: 1 to 6). All patients experienced at least grade 3 neutropenia (grade 4 in nine of them), and one patient died of treatment-related sepsis following the initial cycle of chemotherapy. Median survival was 11 months.

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Selected References

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  1. Edmonson J. H., Ryan L. M., Blum R. H., Brooks J. S., Shiraki M., Frytak S., Parkinson D. R. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269–1275. doi: 10.1200/JCO.1993.11.7.1269. [DOI] [PubMed] [Google Scholar]
  2. Heinrich Michael C., Blanke Charles D., Druker Brian J., Corless Christopher L. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol. 2002 Mar 15;20(6):1692–1703. doi: 10.1200/JCO.2002.20.6.1692. [DOI] [PubMed] [Google Scholar]
  3. Ladanyi Marc, Antonescu Cristina R., Leung Denis H., Woodruff James M., Kawai Akira, Healey John H., Brennan Murray F., Bridge Julia A., Neff James R., Barr Frederic G. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res. 2002 Jan 1;62(1):135–140. [PubMed] [Google Scholar]
  4. Lewis J. J., Antonescu C. R., Leung D. H., Blumberg D., Healey J. H., Woodruff J. M., Brennan M. F. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000 May;18(10):2087–2094. doi: 10.1200/JCO.2000.18.10.2087. [DOI] [PubMed] [Google Scholar]
  5. Pappo A. S., Fontanesi J., Luo X., Rao B. N., Parham D. M., Hurwitz C., Avery L., Pratt C. B. Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol. 1994 Nov;12(11):2360–2366. doi: 10.1200/JCO.1994.12.11.2360. [DOI] [PubMed] [Google Scholar]
  6. Rosen G., Forscher C., Lowenbraun S., Eilber F., Eckardt J., Holmes C., Fu Y. S. Synovial sarcoma. Uniform response of metastases to high dose ifosfamide. Cancer. 1994 May 15;73(10):2506–2511. doi: 10.1002/1097-0142(19940515)73:10<2506::aid-cncr2820731009>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  7. Shiraki M., Enterline H. T., Brooks J. J., Cooper N. S., Hirschl S., Roth J. A., Rao U. N., Enzinger F. M., Amato D. A., Borden E. C. Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience. Cancer. 1989 Jul 15;64(2):484–490. doi: 10.1002/1097-0142(19890715)64:2<484::aid-cncr2820640223>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  8. Trassard M., Le Doussal V., Hacène K., Terrier P., Ranchère D., Guillou L., Fiche M., Collin F., Vilain M. O., Bertrand G. Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol. 2001 Jan 15;19(2):525–534. doi: 10.1200/JCO.2001.19.2.525. [DOI] [PubMed] [Google Scholar]
  9. Van Glabbeke M., van Oosterom A. T., Oosterhuis J. W., Mouridsen H., Crowther D., Somers R., Verweij J., Santoro A., Buesa J., Tursz T. Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 1999 Jan;17(1):150–157. doi: 10.1200/JCO.1999.17.1.150. [DOI] [PubMed] [Google Scholar]

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