The role of chemotherapy in malignant mixed mullerian tumors of the female genital tract

Thirteen patients with malignant mixed mullerian tumor of the female genital tract, treated and followed in our clinic from 1989 to 1999 were retrospectively evaluated. Seven patients (53.8%) with advanced disease or postoperative residual tumor were treated with adjuvant chemotherapy. The median age at diagnosis was 64 years (range: 26-79). All patients underwent primary surgical cytoreduction. Tumors were localized to the endometrium in five (62.5%), to the ovaries in two (25%) and to the fallopian tube in one (12.5%) patient. One patient with endometrial carcinosarcoma had a simultaneous second primary ovarian epithelial carcinoma. Two patients (25%) had a heterologous sarcomatous component. Myometrial involvement included less than half the thickness in one patient, while there was no myometrial invasion encountered in two patients. Five patients (38.5%) had more than 50% of the myometrium invaded. Two patients received additional radiotherapy. Six patients received cisplatinum-based chemotherapy (4 had doxorubicin including combinations), while one patient was treated with a doxorubicin+ifosphamide combination. Five patients (71.4%) had a complete response (CR) to chemotherapy. Response duration in patients with a CR was +13, +67, +10, +14 and +2 months, respectively. After a median follow-up period of 20 months (3-115 months), six patients have died, five are being followed-up with no evidence of disease, one is alive with metastatic disease and one patient is under treatment. Malignant mixed mullerian tumor of the female genital tract is highly responsive to multimodality treatment strategies. Further prospective studies are required to identify distinct prognostic groups that may benefit from various treatment modalities.

Malignant mixed mullerian tumor; Gynecologic; Chemotherapy

[1] Blom R., Guerrieri C., Stal O. et al.: "Malignant mixed mullenan tumors of the uterus : a clinicopathologic, DNA flow cytometric, p53, and rndm-2 analysis of 44 cases". Gynecol. Oncol., 1998, 68,18.

[2] Iwasa Y., Haga H., Konishi I. et al.: "Prognostic factors in utenne carcinosarcoma". Cancer, 1998, 82, 512.

[3] Urtin J.P., Silverberg S. G.,T higpen J. T.,S panos W. J.: "Corpus mesenchyrnal tumors". In: Principles and Practice of Gynecologic Oncology (eds.) Hoskins WJ,P erez CA, Young RC. 2"" Edition. Philadelphia: Lippincott-Raven Publishers, 1997, 897.

[4] Gerszten K., Faul C., Kounelis S., Huang Q., Kelley J., Jones M.W.: "The impact of adjuvant radiotherapy on carcinosarcoma of the uterus". Gyn. Oncol., 1998, 68, 8.

[5] Knocke T. H.,W eitmann H. D.,K ucera H.,K i:ilbl H.,P okrajac B., Potter R.: "Results of primary and adjuvant radiotherapy in the treatment of mixed mullerian tumors of the corpus uteri". Gynecol. Oneal., 1999, 73, 389.

[6] Bieber A., Levenback C., Silva E. G.,B urke T. W.,M orris M., Gershenson D. M.: "Ovarian malignant mixed mullerian tumors treated with platinum-based chemotherapy". Obstet. Gynecol., 1995, 85,735.

[7] Krishnan E.,C oleman R. E.: "Malignant mixed mullerian tumors of gynaecological origin: chemosensitive but aggressive tumors" Clin. Oneal. (R. Coll. Radiol.), 1998, 10(4), 246.

[8] Nordal R.R.,K ristensen G. B.,S tenwigA . E.,N esland J.M.,P ettersen E. O., Trope C. G.: "An evaluation of prognostic factors in uterine carcinosarcoma". Gynecol. Oncol., 1997, 67, 316.

[9] Barakat R. R.,R ubin S. C., Wong G., Saipo P. E., Hoskins W. J "Mixed mesodermal tumors of the ovary: Analysis of prognostic factors in 31 cases". Obstet. Gynecol., 1992, 80, 660.

[10] Muntz H. G., Jones M.A., Goff B. A. et al.: "Malignant mixed mullerian tumors of the ovary: experience with surgical cytoreduction and combination chemotherapy". Cancer, 1995, 76, 1209.

[11] Nielsen S. N.,P odratz K. C., Scheithauer B. W.,O 'Brien P. C.: "Clinicopathologic analysis of uterine malignant mixed mullerian tumors". Gynecol. Oncol., 1989, 34, 372.

[12] Thigpen J. T.,B lessing J.A .,O rr J. W.,D iSaia P. J.: "Phase II trial of cisplatin in the treatment of patients with advanced or recurrent mixed mesodermal sarcomas of the uterus: a Gynecologic Oncology Group Study". Cancer Treat. Rep., 1986, 70, 271.

[13] Gershenson D. M.,K avanagh J. J.,C opeland L. J.,E dwards C. L.. Stringer C. A., W harton J. T.: "Cisplatin therapy for mixed mesodermal sarcomas of the uterus". J. Clin. Oneal., 1987, 59, 1264.

[14] Sutton G. P.,B lessing J. A.,R osenheim N.,P hotopulos G.,D iSaia P. J.: "Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group Study)" Am. J. Obstet. Gynecol., 1989, 161, 309.

[15] Omura G. A.,M ajor F. J.,B lessing J.A . et al.: "A randomized study of adriamycin with or without dimethyl triazinoimidazole carboxa mide in advanced uterine sarcomas". Cancer, 1983, 52, 626.

[16] Muss H.B.,B undy B.,D iSaia P. J. et al.:'Treatment of recurrent or advanced uterine sarcoma". Cancer, 1985, 55, 1648.

[17] Sutton G.,B runetto V. L., Kilgore L. et al.: "A phase Ill trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study". Gynecol. Oncol., 2000, 79, 147.

[18] Plaxe S. C., Dottino P.R., Goodman H. M., Deligdish L., ldel son M., Cohen C. J.: "Clinical features of advanced ovarian mixed mesodermal tumors and treatment with doxorubicin- and cisplatinum- based chemotherapy". Gynecol. Oncol., 1990, 37, 244.

[19] Sutton G.,B lessing J., Homesley H.,M alfetano J.: "A phase II trial of ifosfamide and mesna in patients with advanced or recurrent mixed mesodermal tumors of the ovary previously treated with platinum-based chemotherapy: a Gynecologic Oncology Group Study". Gynecol. Oncol., 1994, 53, 24.

[20] Sood A. K., Sorosky J. I., Gelder M. S. et al.: "Primary ovanan sarcoma". Cancer, 1998, 82, 1731.

[21] Baker T.,P iver M.,C aglar H.,P iedmonte M.: "Prospective trial or cisplatin, adriamycin and dacarbazine in metastatic mixed meso-dermal sarcomas of the uterus and ovary". Am. J. Clin. Oncol., 1991, 9, 246.

[22] Sit A. S. Y.,P rice F. V., Kelley J. L. et al.: "Chemotherapy for malignant mixed mesodermal tumors of the ovary". Gynecol Oncol., 2000, 79, 196.