A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed müllerian tumors with evaluation of potential molecular targets.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007150:Immunohistochemistry; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000188:drug therapy* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D002945:Cisplatin; D007069:Ifosfamide; D015080:Mesna; D018719:Erb-b2 Receptor Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone