Synovial sarcoma. Uniform response of metastases to high dose ifosfamide

Abstract

Background. This report describes the unusually high response rate of metastatic synovial sarcoma to high dose ifosfamide (14–18 g/m2) when that drug was used to treat 13 consecutive patients with recurrent metastatic synovial sarcoma before surgery (or thoracotomies) to provide optimal salvage therapy for these patients. Patients and Methods. Thirteen patients with recurrent or pulmonary metastatic synovial sarcoma seen at the Cedars‐Sinai Comprehensive Cancer Center (Los Angeles, CA) from April, 1989 through January, 1993 were treated with high dose ifosfamide (14–18 g/m2). Ifosfamide was infused at the dose of 2 g/m2 over a 4‐hour bolus infusion, followed by 2‐g/m2 24‐hour continuous infusions of ifosfamide, for a total of 14 or 18 g/m2 (6–8 days). Mesna (Mesnex, Bristol‐Myers Oncology, Princeton, NJ) was infused with the ifosfamide at equimolar doses. Supplemental sodium bicarbonate (180 mEq) was given daily to prevent severe acidosis. Nine of the thirteen patients were treated with prior chemotherapy for their primary tumors. Prior chemotherapy consisted of doxorubicin (Adriamycin, Adria Labs, Dublin, OH) in all patients and doxorubicin combined with cisplatin in eight of them. Results. All 13 patients had objective responses to high dose ifosfamide chemotherapy. There were nine partial responses and four complete responses. Five of the patients died of disease at 20–40 months (median, 27 months) from initial therapy. Eight patients have survived from 2 to 43 months (median, 20 months) from initial therapy, and three of these patients are disease free. Those patients surviving disease free had successful surgical removal of their residual metastatic disease after chemotherapy. Conclusion. Metastatic synovial sarcoma appears to be particularly sensitive to high dose ifosfamide chemotherapy. This experience suggests that there is a role for high dose ifosfamide chemotherapy in preoperative and postoperative adjuvant chemotherapy for primary synovial sarcoma, which is usually always a high grade malignant lesion with a poor prognosis after surgery alone.

Synovial Sarcoma of the Upper Digestive Tract: A Report of Two Cases with Demonstration of the X;18 Translocation by Fluorescence In Situ Hybridization

“…The distinction has therapeutic implications as well. Synovial sarcoma may respond to adjuvant chemotherapy with regimens including high-dose ifosfamide (35,36).…”

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas

“…[7][8][9] For ifosfamide a dose response has been documented. [10][11][12][13] Another active single agent in the therapy of STS is cisplatin with a 15% response rate using high doses (200 mg/m 2 ). 14,15 In phase-II studies different combination chemotherapy regimens based on high doses of ifosfamide, doxorubicin or cisplatin demonstrated response rates of up to 60%.…”

Chemotherapy for adult soft tissue sarcoma

“…Other agents, including cyclophosphamide, DTIC and dactinomycin, have single agent response rates in the H>-20% range [3]. Ifosfamide is a particularly valuable agent due to its non-cross resistance with doxorubicin and cyclophosphamide [3,4].…”

“…There are indications that some cytostatic agents may have higher activity for certain histological types, including ifosfamide and doxorubicin for synovial sarcomas [4,10], and OTIC-containing combinations for leiomyosarcomas [II,12].…”

“…A positive relationship is indicated in both phase II and randomized studies with other primary end points, with response rates for doxorubicin increasing with dose to approximately 25% at 75 mg/m 2 /course [19]. For ifosfamide, a dose-response relationship is suggested by several phase II studies [19,22], and with high-dose treatment ( 14-18 g/m 2 ) including haematopoietic growth factor support, response rates of 33-l 00% have been reported in heavily pretreated patients [4,23,24]. Also, several preliminary communications have reported objective responses in patients who have previously failed on lower dose levels of ifosfamide, which is supportive of a dose-response relationship [23,25].…”