mesna and Carcinosarcoma

After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies.. Eligible, consenting women with stage I-IV uterine CS, no more than 1 cm postsurgical residuum and/or no extra-abdominal spread had their treatments randomly assigned as either WAI or three cycles of cisplatin (C), ifosfamide (I), and mesna (M).. 232 patients were enrolled, of whom 206 (WAI=105; CIM=101) were deemed eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I=64 (31%); II=26 (13%); III=92 (45%); IV=24 (12%). The estimated crude probability of recurring within 5 years was 58% (WAI) and 52% (CIM). Adjusting for stage and age, the recurrence rate was 21% lower for CIM patients than for WAI patients (relative hazard [RH]=0.789, 95% confidence interval [CI]: (0.530-1.176), p=0.245, 2-tail test). The estimated death rate was 29% lower among the CIM group (RH=0.712, 95% CI: 0.484-1.048, p=0.085, two-tail test).. We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS. However, the observed differences favor the use of combination chemotherapy in future trials.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinosarcoma; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Female; Humans; Hysterectomy; Ifosfamide; Incidence; Mesna; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Protective Agents; Radiotherapy, Adjuvant; Risk Factors; Survival Analysis; Treatment Failure; Treatment Outcome; Uterine Neoplasms

A retrospective study to evaluate six cycles of cisplatin 40 mg/m2 on day 1 and ifosfamide 1,200 mg/m2 daily on days 1 to 4 with Mesna every four weeks as first line treatment for 29 patients with a diagnosis of uterine carcinosarcoma.. A total of 23 of 29 patients received high dose rate intracavitary vaginal cuff brachytherapy (VCBT) with two fractions of seven Gy each. Median age was 65 years (range 40-82); 13 (44.8%) had Stage I disease, three (10.3%) had Stage II, eight (27.6%) had Stage III, and five (17.2%) patients had Stage IV disease.. Most common toxicities were anemia grade 1 (35%)/grade 2 (45%), and neutropenia grade 3 (17%)/grade 4 (6.9%). Eleven dose modifications, four treatment discontinuations, and one patient withdrawal occurred. At a median follow up of 45 months (range 9 to 144), Progression free survival (PFS) was 20% and overall survival (OS) was 40% for Stage IV, PFS 75% and OS 62.5% for Stage III, compared to a PFS 75% and OS 72.2% for Stages I-II. Median OS for the entire group was 12.43 years (95% CI 3.69 to inf); for Stage I-III 12.4 years (6.1 to inf), and for Stage IV 15.6 months (95% CI 9.4 to inf).. Cisplatin and ifosfamide chemotherapy with VCBT was well tolerated and has promising activity in uterine carcinosarcoma.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinosarcoma; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Protective Agents; Retrospective Studies; Treatment Outcome; Uterine Neoplasms

Uterine carcinosarcomas (UCSs) are highly aggressive, rare, biphasic tumors composed of epithelial and mesenchymal elements. Surgery remains the mainstay of treatment in early-stage disease. Adjuvant pelvic radiotherapy improves locoregional control without proven overall survival (OS) benefit. Although adjuvant ifosfamide-based combination chemotherapy with cisplatin or paclitaxel has shown superiority to radiotherapy or single-agent chemotherapy in randomized controlled trials, there is no consensus on a standard regimen due to toxicities. The aim of this retrospective study was to assess the efficacy and toxicity of a novel combination chemotherapy using carboplatin, ifosfamide and mesna (CIM) and compare with other regimens for patients with UCSs in both the adjuvant and palliative setting.. Between 1997 and 2010, 60 patients with UCS, 70% of whom with international federation of gynecology and obstetrics (FIGO) stage III/IV disease, were treated with adjuvant or palliative chemotherapy. Two groups were identified: Group1 (n=22) included patients receiving CIM chemotherapy; and group 2 (n=38) receiving other regimens (carboplatin/paclitaxel/cisplatin/doxorubicin/epirubicin).. After a median follow-up of 60 months, disease in seven patients in group 1 (CIM) and 20 patients in group 2 had progressed/relapsed. Out of these, six patients in group 1 and 13 patients in group 2 had died. The progression-free survival (PFS) and OS for patients treated with adjuvant or palliative CIM was 35 months [95% confidence interval (CI) =0.26-0.43] and 47 months (95% CI=0.38-0.56; log-rank, p=0.001) respectively, whereas for group 2 patients treated with other regimens, PFS was 27.48 months (95% CI=0.20-0.33) and OS was 30 months (95% CI=0.21-0.38; log-rank, p=0.001). While none of the patients in group 1 experienced neurotoxicity or other grade 3 or 4 toxicities, 3/38 patients in group 2 experienced grade 3 neutropenia, 4/38 had peripheral sensory neuropathy, 6/38 patients had treatment deferred due to toxicities or allergic reaction to paclitaxel.. In the phase III randomized controlled trial combination of ifosfamide and taxanes has shown PFS and OS benefit when compared to single-agent ifosfamide at the expense of significant toxicities. Results from our study show that the combination of CIM is an effective and safe alternative regimen for patients with advanced UCSs. In addition to improved OS and PFS, the main advantage of this regimen over taxane-based regimens includes minimal neuropathy, less use of steroids, and low risk of allergic reaction. CIM should be considered in future prospective studies looking at the treatment of UCS.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinosarcoma; Demography; Disease-Free Survival; Female; Humans; Ifosfamide; Mesna; Middle Aged; Retrospective Studies; Treatment Outcome; Uterine Neoplasms

Topics: Animals; Antidotes; Carcinosarcoma; Cyclophosphamide; Ifosfamide; Mercaptoethanol; Mesna; Phosphoramide Mustards; Rats; Urine