mesna and Mixed-Tumor--Mullerian

The aim of this study was to determine the efficacy of cisplatin, ifosfamide, and mesna in uterine malignant mixed müllerian tumor (MMMT) and to evaluate the expression of clinically relevant molecular markers.. Women with advanced or recurrent MMMT were treated every 28 days with cisplatin (75 mg/m(2)), ifosfamide (1.2 gm/m(2)), and mesna (240 mg/m(2)). Treatment continued until disease progression or for six courses in the case of nonmeasurable disease. Immunohistochemical analysis for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, C-kit, Abl, and PDGFR-beta expression were performed.. Sixteen patients received 1-10 cycles; 2 died of disease progression after 1 cycle; 3 stopped after 1 cycle because of toxicity. Of 6 with measurable disease, 2 had a partial response, 1 had stable disease (SD), and 3 had progression (RR 33%). Partial response durations were 6 and 9 months; SD duration was 6 months. Of 5 patients without measurable disease, 4 received 6 cycles; 1 received 4 cycles. Four died of recurrent disease and 1 was without disease 6.5 years after treatment. Thirty-six percent experienced at least one neutropenic G3 or G4 event. All experienced G1 gastrointestinal toxicity. Four required dose reductions. At 7.5 months, only 1 with measurable disease was still living. Immunohistochemical analyses revealed that 24% expressed ER or PR, 19% expressed HER-2/neu, and none expressed C-kit. However, 45% expressed Abl and 100% expressed PDGFR-beta.. Although the combination of cisplatin, ifosfamide, and mesna in patients with MMMT had moderate activity, the high toxicity and short response duration in this uncommon, aggressive malignancy suggest that this regiment continues to be a disappointing treatment choice for uterine MMMT. HER-2/Neu, Abl, or PDGFR-beta expression may be of value in order to investigate novel multimodality treatment strategies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Ifosfamide; Immunohistochemistry; Mesna; Middle Aged; Mixed Tumor, Mullerian; Receptor, ErbB-2; Receptor, Platelet-Derived Growth Factor beta; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms

The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas.. Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion.. The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction.. Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Adjuvant; Female; Humans; Ifosfamide; Infusions, Intravenous; Leiomyosarcoma; Mesna; Middle Aged; Mixed Tumor, Mullerian; Neoplasm Staging; Protective Agents; Rhabdomyosarcoma; Sarcoma; Survival Analysis; Uterine Neoplasms

Malignant mixed müllerian tumors (MMMT) of the ovary are rare, aggressive and rapidly progressive tumors. According to the available literature, the presence of metastatic disease rarely permits long term survival. We report on a 64-year old patient with stage IV ovarian MMMT who achieved a surgically-documented complete response (CR) after 6 cycles of carboplatin, mesna, ifosfamide, cis-platin. Pelvic recurrence was diagnosed 14 months later; the patient received 6 cycles of the same regimen used as first-line chemotherapy which resulted in a second complete response lasting for 4 months. The patient died 37 months after initial diagnosis due to intestinal occlusion. In the current case Ca 125 was significantly increased at clinical presentation of disease but not at the time of recurrence.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Combined Modality Therapy; Female; Humans; Ifosfamide; Mesna; Mice; Middle Aged; Mixed Tumor, Mullerian; Neoplasm Staging; Ovarian Neoplasms

Four patients with metastatic ovarian mixed Müllerian sarcoma (2 homologous, 2 heterologous) were treated with mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy. Two of four patients had optimal debulking. Three of four patients responded to chemotherapy, with two complete responses of 34- and 46-month duration. The MAID regimen appears to be active in patients with ovarian sarcoma.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Mixed Tumor, Mullerian; Ovarian Neoplasms; Sarcoma; Treatment Outcome