Chemotherapy for uterine sarcoma – pro
Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2% to 5% of all uterine malignancies. Surgery alone can be curative if the malignancy is contained within the uterus. The value of pelvic radiation therapy is not established. Current studies consist primarily of Phase II chemotherapy trials for advanced disease. Adjuvant chemotherapy following complete resection (stage I and II) has not been established to be effective in a randomized trial. Yet, other nonrandomized trials have reported improved survival following adjuvant chemotherapy with or without radiation therapy.
For metastatic disease, Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for advanced disease. Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas (mixed mesodermal tumors), but is inactive as first- or second-line therapy of leiomyosarcoma. Patients who present with measurable disease have been treated on a series of Phase II studies by the Gynecologic Oncology Group (GOG). In separate studies of patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in mixed mesodermal tumors , a 33% response rate in endometrial stromal cell sarcomas, and a 17.2% partial response rate in leiomyosarcomas. The GOG has also completed a randomized comparison of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcoma (mixed mesodermal tumor). The study demonstrated a higher response rate and longer progression-free survival on the combination arm. Survival, however, was not improved by the addition of cisplatin, and the authors concluded that use of the combination was not justified because of increased toxic effects. However, about one-third of patients with metastatic gynecological sarcomas may derive some palliative benefit from chemotherapy, especially in stromal tumors which appear to respons better.
For metastatic disease, Doxorubicin(Adriamycin) in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for advanced disease. Patients who present with measurable disease have been treated on a series of Phase II studies by the Gynecologic Oncology Group (GOG). In separate studies of patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in mixed mesodermal tumors , a 33% response rate in endometrial stromal cell sarcomas, and a 17.2% partial response rate in leiomyosarcomas. The GOG has also completed a randomized comparison of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcoma (mixed mesodermal tumor). The study demonstrated a higher response rate and longer progression-free survival on the combination arm. About one-third of patients with metastatic gynecological sarcomas may derive some palliative benefit from chemotherapy, especially in stromal tumors which appear to respond better. However, NCCN does not recommend this particular combination for uterine sarcoma or soft tissue sarcoma. A recent guideline(Verma et al) says: “In patients with metastatic sts, the addition of ifosfamide to standard first-line doxorubicin-containing regimens is not recommended over single-agent doxorubicin.However, in patients with symptomatic, locally advanced, or inoperable sts, in whom tumour response might potentially result in reduced symptomatology or render a tumour resectable, use of ifosfamide in combination with doxorubicin is reasonable.”
The NCCN cites cisplatin and Taxol separately but also states that the options they list can be used in combination, when appropriate. This is so stated probably because NCCN supports the use of chemotherapy for metastatic uterine sarcoma but there is a paucity of randomized trials to enable a recommendation of specific regimens. For us this presents a probelm in determining necessity. On the balance, I consider the proposed regimen to yes be med. necessary.
nccn.org, uterine
S. Kanjeeka et al Metastatic uterine sarcoma: A systematic review of the literature. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 5105
Sindu Kanjeekal, Alexandra Chambers, Michael Fung Kee Fung, Shailendra Verma and Program in Evidence-based Care, Cancer Care Ontario, Canada on behalf of the Cancer Care Ontario Practice Guidelines Initiative Gynecology Cancer Disease Site Group
Systemic therapy for advanced uterine sarcoma: A systematic review of the literature
Gynecologic Oncology, Volume 97, Issue 2, May 2005, Pages 624-637