Table of Contents Purpose of This PDQ Summary General Information About Uterine Sarcoma
Cellular Classification of Uterine Sarcoma Stage Information for Uterine Sarcoma Treatment Option Overview Stage I Uterine Sarcoma Stage II Uterine Sarcoma Stage III Uterine Sarcoma Stage IV Uterine Sarcoma Recurrent Uterine Sarcoma Get More Information From NCI Changes to This Summary (05/22/2008) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of uterine sarcoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Risk factors.
- Prognosis.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information About Uterine Sarcoma
Related Summaries
Other PDQ summaries containing information related to uterine sarcoma include:
Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2% to 5%
of all uterine malignancies.[1] The following tumors arise primarily from three distinct
tissues:
- Carcinosarcomas arising in the endometrium, in other organs of mullerian origin, and accounting for 40% to 50% of all uterine sarcomas.
- Leiomyosarcomas arising from myometrial muscle, with a peak incidence occurring at age 50, and accounting for 30% of all uterine sarcomas.
- Sarcomas arising in the endometrial stroma, with a peak incidence occurring before menopause for the low-grade tumors and after menopause for the high-grade tumors, and accounting for 15% of all uterine sarcomas.
The three distinct entities are often grouped under uterine sarcomas; however, each type of tumor is currently being studied in separate clinical trials.
Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal sarcomas or mullerian tumors. Controversy exists about the following issues:
- Whether they are true sarcomas.
- Whether the sarcomatous elements are actually derived from a common epithelial cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.
The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements (such as malignant mesenchymal tissue considered possibly native to the uterus) or heterologous elements (such as striated muscle, cartilage, or bone, which are foreign to the uterus). Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.
Other rare forms of uterine sarcomas also fall under the WHO classification of mesenchymal and mixed tumors of the uterus. These include mixed endometrial stromal and smooth muscle tumors, adenosarcomas (where the epithelial elements appear benign within a malignant mesenchymal background), embryonal botroydes or rhabdomyosarcomas (found almost exclusively in infants), and the latest addition, PEComa—a perivascular epithelial-cell tumor that may behave in a malignant fashion.[2,3] (Refer to the PDQ summary on Childhood Rhabdomyosarcoma for more information.)
Risk Factors
The only documented
etiologic factor in 10% to 25% of these malignancies is prior pelvic radiation therapy,
which is often administered for benign uterine bleeding that began 5 to 25 years earlier.
An increased incidence of uterine sarcoma has been associated with tamoxifen in the treatment of breast cancer. Subsequently, increases have also been noted when tamoxifen was given to prevent breast cancer in women at increased risk—a possible result of the estrogenic effect of tamoxifen on the uterus. Because of this increase, patients on tamoxifen should have follow-up pelvic examinations and should undergo endometrial biopsy if there is any abnormal uterine bleeding.[4-6]
Prognosis
The prognosis for women with uterine sarcoma is primarily dependent on the extent of
disease at the time of diagnosis.[7] For women with carcinosarcomas, significant
predictors of metastatic disease at initial surgery include isthmic or cervical location, lymphatic vascular space invasion,
serous and clear cell histology, and grade 2 or 3 carcinoma.[7] These factors, along
with adnexal spread, lymph node metastases, tumor size, peritoneal cytologic
findings, and depth of myometrial invasion correlate with progression-free
interval.[7] The presence or absence of stromal heterologous elements, the
types of such elements, the grade of the stromal components, and the mitotic
activity of the stromal components bear no relationship to the presence or
absence of metastases at surgical exploration. However, in one study, women
with a well-differentiated sarcomatous component or carcinosarcomas had
significantly longer progression-free intervals than those with moderately to
poorly differentiated sarcomas for the homologous and heterologous types.
The recurrence rate was 44% for homologous tumors and 63% for heterologous
tumors. The type of heterologous sarcoma had no effect on the progression-free
interval.
For women with leiomyosarcomas, some investigators consider tumor size to be the most
important prognostic factor; women with tumors greater than 5.0 cm in maximum
diameter have a poor prognosis.[8] However, in a Gynecologic Oncology Group
study, the mitotic index was the only factor significantly related to
progression-free interval.[7] Leiomyosarcomas matched for other known
prognostic factors may be more aggressive than their carcinosarcoma
counterparts.[9] The 5-year survival rate for women with stage I disease, which is
confined to the corpus, is approximately 50% versus 0% to 20% for the remaining
stages.
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 patients with advanced disease. Adjuvant
chemotherapy following complete resection for patients with stage I or II disease was not established to be effective in a randomized trial.[10] Yet, other nonrandomized
trials have reported improved survival following adjuvant chemotherapy with or
without radiation therapy.[11-13]
References
-
Forney JP, Buschbaum HJ: Classifying, staging, and treating uterine sarcomas. Contemp Ob Gyn 18(3):47, 50, 55-56, 61-62, 64, 69, 1981.
-
Gershenson D, McGuire W, Gore Martin, et al.: Gynecologic Cancer: Controversies in Management. 3rd ed. New York, NY: Churchill Livingstone, 2004.
-
Tavassoéli F, Devilee P, et al.: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: International Agency for Research on Cancer, 2004.
-
Bergman L, Beelen ML, Gallee MP, et al.: Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 356 (9233): 881-7, 2000.
[PUBMED Abstract]
-
Cohen I: Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 94 (2): 256-66, 2004.
[PUBMED Abstract]
-
Wickerham DL, Fisher B, Wolmark N, et al.: Association of tamoxifen and uterine sarcoma. J Clin Oncol 20 (11): 2758-60, 2002.
[PUBMED Abstract]
-
Major FJ, Blessing JA, Silverberg SG, et al.: Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 71 (4 Suppl): 1702-9, 1993.
[PUBMED Abstract]
-
Evans HL, Chawla SP, Simpson C, et al.: Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer 62 (10): 2239-47, 1988.
[PUBMED Abstract]
-
Oláh KS, Dunn JA, Gee H: Leiomyosarcomas have a poorer prognosis than mixed mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynaecol 99 (7): 590-4, 1992.
[PUBMED Abstract]
-
Omura GA, Blessing JA, Major F, et al.: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 3 (9): 1240-5, 1985.
[PUBMED Abstract]
-
Piver MS, Lele SB, Marchetti DL, et al.: Effect of adjuvant chemotherapy on time to recurrence and survival of stage I uterine sarcomas. J Surg Oncol 38 (4): 233-9, 1988.
[PUBMED Abstract]
-
van Nagell JR Jr, Hanson MB, Donaldson ES, et al.: Adjuvant vincristine, dactinomycin, and cyclophosphamide therapy in stage I uterine sarcomas. A pilot study. Cancer 57 (8): 1451-4, 1986.
[PUBMED Abstract]
-
Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989.
[PUBMED Abstract]
Back to Top Cellular Classification of Uterine Sarcoma
The most common histologic types of uterine sarcomas are:
- Carcinosarcomas (mixed
mesodermal sarcomas [40%–50%]).
- Leiomyosarcomas (30%).
- Endometrial stromal
sarcomas (15%).
The uterine neoplasm classification of the International Society of
Gynecologic Pathologists and the World Health Organization uses the term carcinosarcomas for all primary uterine
neoplasms containing malignant elements of both epithelial and stromal light
microscopic appearances, regardless of whether malignant heterologous
elements are present.[1]
References
-
Silverberg SG, Major FJ, Blessing JA, et al.: Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 9 (1): 1-19, 1990.
[PUBMED Abstract]
Back to Top Stage Information for Uterine Sarcoma
The FIGO staging for carcinoma of the corpus uteri has been applied to uterine
sarcoma.[1]
Stage I
Stage I sarcoma is confined to the corpus uteri. This stage accounts for 50%
of all presentations.
- Stage IA: tumor limited to endometrium.
- Stage IB: invasion to less than 50% of the myometrium.
- Stage IC: invasion to more than 50% of the myometrium.
Stage II
Stage II uterine sarcoma means the cancer has involved the corpus and the
cervix but has not extended outside the uterus.
- Stage IIA: endocervical glandular involvement only.
- Stage IIB: cervical stromal invasion.
Stage III
Stage III uterine sarcoma means extension outside of the uterus but confined to
the true pelvis.
- Stage IIIA: tumor invades serosa and/or adnexae and/or positive peritoneal
cytology.
- Stage IIIB: metastases to pelvic and/or para-aortic lymph nodes.
Stage IV
Stage IV uterine sarcoma means involvement of the bladder or bowel mucosa or
metastasis to distant sites.
- Stage IVA: tumor invasion of bladder and/or bowel mucosa.
- Stage IVB: distant metastases, including intra-abdominal and/or inguinal
lymph nodes.
References
-
Shepherd JH: Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 96 (8): 889-92, 1989.
[PUBMED Abstract]
Back to Top Treatment Option Overview
Surgery is often the principal means of diagnosis and is the primary treatment for all patients with uterine sarcoma. If the diagnosis is known, the extent of surgery is planned according to the stage of the tumor. Hysterectomy is usually performed when a uterine malignancy is suspected, except for rare instances when preservation of the uterus in a young patient is deemed safe for the type of cancer (e.g., a totally confined low-grade leiomyosarcoma in a woman who desires to retain childbearing potential). Medically suitable patients with the preoperative diagnosis of uterine sarcoma
are considered candidates for abdominal hysterectomy, bilateral
salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy.
Cytologic washings are obtained from the pelvis and abdomen. Thorough
examination of the diaphragm, omentum, and upper abdomen is performed.
There is no firm evidence from a prospective study that adjuvant chemotherapy
or radiation therapy is of benefit for patients with uterine sarcoma.[1]
In one Gynecologic Oncology Group (GOG) study, the use of adjuvant doxorubicin did not alter the survival rate of patients with resected stage I or stage II uterine sarcomas; however, interpretation of these results is difficult because this study included some patients who received radiation and three types of uterine sarcomas that have variable responses to doxorubicin.[1][Level of evidence: 1iiA] However, because the risk of disease recurrence is high even with localized
presentations, many physicians have considered the use of adjuvant chemotherapy
or radiation therapy.[2]
A report of a study (GOG-150) that addressed radiation therapy versus adjuvant chemotherapy is awaited.[3]
References
-
Omura GA, Blessing JA, Major F, et al.: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 3 (9): 1240-5, 1985.
[PUBMED Abstract]
-
Kohorn EI, Schwartz PE, Chambers JT, et al.: Adjuvant therapy in mixed mullerian tumors of the uterus. Gynecol Oncol 23 (2): 212-21, 1986.
[PUBMED Abstract]
-
Wolfson AH, Brady MF, Mannel RS, et al.: A Gynecologic Oncology Group randomized trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide+mesna (CIM) in optimally debulked stage I-IV carcinosarcoma (CS) of the uterus. [Abstract] J Clin Oncol 24 (Suppl 18): A-5001, 256s, 2006.
Back to Top Stage I Uterine Sarcoma
Standard treatment options:
- Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
pelvic and periaortic selective lymphadenectomy).
- Surgery plus pelvic radiation therapy.
- Surgery plus adjuvant chemotherapy.
- Surgery plus adjuvant radiation therapy as seen in the EORTC-55874 trial, for example.
In a nonrandomized Gynecologic Oncology Group study in patients with stage I
and II carcinosarcomas, those who had pelvic radiation therapy had a significant
reduction of recurrences within the radiation treatment field but no alteration
in survival.[1] A large nonrandomized study demonstrated improved survival and
a lower local failure rate in patients with mixed mullerian tumors following
postoperative external and intracavitary radiation therapy.[2] One
nonrandomized study that predominantly included patients with carcinosarcomas appeared to show benefit for adjuvant therapy with cisplatin
and doxorubicin.[3]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I uterine sarcoma. 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
-
Hornback NB, Omura G, Major FJ: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int J Radiat Oncol Biol Phys 12 (12): 2127-30, 1986.
[PUBMED Abstract]
-
Larson B, Silfverswärd C, Nilsson B, et al.: Mixed müllerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases. Radiother Oncol 17 (2): 123-32, 1990.
[PUBMED Abstract]
-
Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989.
[PUBMED Abstract]
Back to Top Stage II Uterine Sarcoma
Standard treatment options:
- Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
pelvic and periaortic selective lymphadenectomy).
- Surgery plus pelvic radiation therapy.
- Surgery plus adjuvant chemotherapy.
- Surgery plus adjuvant radiation therapy (EORTC-55874).
In a nonrandomized Gynecologic Oncology Group study in patients with stage I
and II carcinosarcomas, those who had pelvic radiation therapy had a significant
reduction of recurrences within the radiation treatment field but no alteration
in survival.[1] One nonrandomized study that predominantly included patients with carcinosarcomas appeared to show benefit for adjuvant
therapy with cisplatin and doxorubicin.[2]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II uterine sarcoma. 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
-
Hornback NB, Omura G, Major FJ: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int J Radiat Oncol Biol Phys 12 (12): 2127-30, 1986.
[PUBMED Abstract]
-
Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989.
[PUBMED Abstract]
Back to Top Stage III Uterine Sarcoma
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Standard treatment options:
- Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy,
pelvic and periaortic selective lymphadenectomy, and resection of all gross
tumor).
Treatment options under clinical evaluation:
- Surgery plus pelvic radiation therapy.
- Surgery plus adjuvant chemotherapy.
Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal or mullerian tumors. Controversy exists about the following issues:
- Whether they are true sarcomas.
- Whether the sarcomatous elements are actually derived from a common epithelial cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.
The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements (such as malignant mesenchymal tissue considered possibly native to the uterus) or heterologous elements (such as striated muscle, cartilage, or bone, which are foreign to the uterus). Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.
Patients who present with uterine sarcoma have been treated on a series of
phase II studies by the Gynecologic Oncology Group including the GOG-87B trial, for example.[1,2]
These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy,
ifosfamide had a 32.2% response rate in patients with carcinosarcomas [3] and a 17.2%
partial response rate in patients with leiomyosarcomas.[2]
A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[4][Level of evidence: 1iiA] The follow-up GOG-161
study
utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4).[5] The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.49–0.97).[5][Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.
A role for chemotherapy as adjuvant to surgery has not yet been established.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III uterine sarcoma. 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
-
Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991.
[PUBMED Abstract]
-
Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992.
[PUBMED Abstract]
-
Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989.
[PUBMED Abstract]
-
Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000.
[PUBMED Abstract]
-
Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007.
[PUBMED Abstract]
Back to Top Stage IV Uterine Sarcoma
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
There is currently no standard therapy for patients with stage IV disease.
These patients should be entered into an ongoing clinical trial.
Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal or mullerian tumors. Controversy exists about the following issues:
- Whether they are true sarcomas.
- Whether the sarcomatous elements are actually derived from a common epithelial cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.
The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements (such as malignant mesenchymal tissue considered possibly native to the uterus) or heterologous elements (such as striated muscle, cartilage, or bone, which is foreign to the uterus). Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.
Patients who present with
uterine sarcoma have been treated on a series of phase II studies by the
Gynecologic Oncology Group including the GOG-87B trial, for example .[1] These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients
previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in
patients with carcinosarcomas,[2] a 33% response rate in patients with endometrial stromal cell
sarcomas,[3], and a 17.2% partial response rate in patients with leiomyosarcomas.[4] Doxorubicin
in combination with dacarbazine or cyclophosphamide is no more active than
doxorubicin alone for advanced disease.[5,6] Cisplatin has activity as
first-line therapy and minimal activity as second-line therapy for patients
with carcinosarcomas, but cisplatin is inactive as first- or
second-line therapy for patients with leiomyosarcomas.[1,7]
A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[8][Level of evidence: 1iiA] The follow-up GOG-161 study
utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4).[9] The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.49–0.97).[9][Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV uterine sarcoma. 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
-
Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991.
[PUBMED Abstract]
-
Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989.
[PUBMED Abstract]
-
Sutton G, Blessing JA, Park R, et al.: Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: a study of the Gynecologic Oncology Group. Obstet Gynecol 87 (5 Pt 1): 747-50, 1996.
[PUBMED Abstract]
-
Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992.
[PUBMED Abstract]
-
Omura GA, Major FJ, Blessing JA, et al.: A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52 (4): 626-32, 1983.
[PUBMED Abstract]
-
Muss HB, Bundy B, DiSaia PJ, et al.: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 55 (8): 1648-53, 1985.
[PUBMED Abstract]
-
Thigpen JT, Blessing JA, Wilbanks GD: Cisplatin as second-line chemotherapy in the treatment of advanced or recurrent leiomyosarcoma of the uterus. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol 9 (1): 18-20, 1986.
[PUBMED Abstract]
-
Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000.
[PUBMED Abstract]
-
Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007.
[PUBMED Abstract]
Back to Top Recurrent Uterine Sarcoma
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
There is currently no standard therapy for patients with recurrent disease.
These patients should be entered into an ongoing clinical trial.
Patients who present with
uterine sarcoma have been treated on a series of phase II studies by the
Gynecologic Oncology Group including the GOG-87B trial, for example. These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in
patients with carcinosarcomas,[1] a 33% response rate in patients with endometrial stromal cell sarcomas,[2] and a 17.2% partial response rate in patients with leiomyosarcomas.[3] Doxorubicin
in combination with dacarbazine or cyclophosphamide is no more active than
doxorubicin alone for recurrent disease.[4,5] Cisplatin has activity as
first-line therapy and minimal activity as second-line therapy for patients
with carcinosarcomas, but cisplatin is inactive as first- or
second-line therapy for patients with leiomyosarcomas.[6,7] A regimen of gemcitabine plus docetaxel had a 53% response rate in patients with unresectable leiomyosarcomas and is undergoing further study.[8]
A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[9][Level of evidence: 1iiA] The follow-up GOG-161 study
utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4).[10] The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.49–0.97).[10][Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.
For patients with carcinosarcomas who have localized recurrence to the pelvis
confirmed by computed tomographic scanning, radiation therapy may be effective
palliation. Phase I and II clinical trials are appropriate for patients who
recur with distant metastasis and are unresponsive to first-line phase II
trials. High-dose progesterone hormone therapy may be of some benefit to
patients with low-grade stromal sarcoma.[11]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent uterine sarcoma. 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
-
Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989.
[PUBMED Abstract]
-
Sutton G, Blessing JA, Park R, et al.: Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: a study of the Gynecologic Oncology Group. Obstet Gynecol 87 (5 Pt 1): 747-50, 1996.
[PUBMED Abstract]
-
Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992.
[PUBMED Abstract]
-
Omura GA, Major FJ, Blessing JA, et al.: A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52 (4): 626-32, 1983.
[PUBMED Abstract]
-
Muss HB, Bundy B, DiSaia PJ, et al.: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 55 (8): 1648-53, 1985.
[PUBMED Abstract]
-
Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991.
[PUBMED Abstract]
-
Thigpen JT, Blessing JA, Wilbanks GD: Cisplatin as second-line chemotherapy in the treatment of advanced or recurrent leiomyosarcoma of the uterus. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol 9 (1): 18-20, 1986.
[PUBMED Abstract]
-
Hensley ML, Maki R, Venkatraman E, et al.: Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 20 (12): 2824-31, 2002.
[PUBMED Abstract]
-
Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000.
[PUBMED Abstract]
-
Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007.
[PUBMED Abstract]
-
Katz L, Merino MJ, Sakamoto H, et al.: Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors. Gynecol Oncol 26 (1): 87-97, 1987.
[PUBMED Abstract]
Back to Top Get More Information From NCI
Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.
Chat online
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:
- NCI Public Inquiries Office
- Suite 3036A
- 6116 Executive Boulevard, MSC8322
- Bethesda, MD 20892-8322
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.
Back to Top Changes to This Summary (05/22/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Back to Top |