mesna and Uterine-Neoplasms

Topics: Adenocarcinoma, Clear Cell; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Papillary; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Lymphatic Metastasis; Mesna; Neoplasms, Second Primary; Radiotherapy, Adjuvant; Thyroid Neoplasms; Thyroidectomy; Uterine Neoplasms; Vincristine

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

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 aim of this study was to verify the efficacy of sodium-2-mercaptoethanesulfonate (mesna) in the chemical separation of tissues in abdominal myomectomies when used with the traditional mechanical separation techniques.. In a prospective, randomized study, 58 women underwent abdominal myomectomy. In 29 of these, we used mesna for highlighting and separating tissues, and in the other 29 we used saline solution for the same purposes. The variables evaluated included the number of myomas removed, the volume of the biggest myoma, and the total volume of the myomas removed in every intervention. We also recorded operating time, the length of hospital stay, the degree of procedure difficulty, perioperative blood loss, operative complications, and cost.. The operation was significantly shorter in the mesna group (p < 0.05) even though the volume and the number of myomas were larger. The degree of difficulty evaluated by the surgeon at the end of every operation was not significantly different in the two groups. The reduction in hemoglobin 24 hours after operation was significantly less in the patients treated with mesna (p = 0.006), but this difference was probably altered by the increase in hematocrit levels.. Because of its ability as a chemical dissector, mesna may be a useful aid in this type of benign gynecologic operation. Larger studies to confirm this are needed.

Topics: Adult; Blood Loss, Surgical; Female; Gynecologic Surgical Procedures; Hematocrit; Humans; Leiomyoma; Length of Stay; Mesna; Prospective Studies; Protective Agents; Uterine Neoplasms

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Multicenter Studies as Topic; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Remission Induction; Uterine Cervical Neoplasms; 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

The prognosis of uterine leiomyosarcoma (LMS) is notoriously poor and a standard chemotherapy for patients with uterine LMS has not yet been established. Here, we describe two patients with recurrent LMS of the uterus who were treated with mesna, doxorubicin, ifosfamide and dacarbazine chemotherapy; one achieved complete and the other partial remission.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Uterine Neoplasms

To report the experience of a single institution in the south of Israel with doxorubicin and ifosfamide-mesna in patients with advanced/recurrent uterine sarcomas.. The hospital records of five patients with advanced/recurrent uterine sarcomas who had combination chemotherapy with doxorubicin and ifosfamide-mesna were retrospectively reviewed. Doxorubicin 30 mg/m2 was given on days 1 and 2 and ifosfamide 2000 mg/m2 (+ mesna, W/W 60%) was given on days 1, 2 and 3 of every 21 days. Dose intensity, relative dose intensity and average relative dose intensity (ARDI) of chemotherapy were calculated. Response was determined using clinical evaluation and radiological reports. Toxicity was graded using the National Cancer Institute (NCI) criteria.. The median ARDI of the combination of doxorubicin and ifosfamide received by the patients was 0.68 (range, 0.53-0.74). One (20%) patient had disease complete response lasting three months and four (80%) patients had progressive disease. Toxicity was mainly hematological with grade 3 or 4 leukopenia--four (80%) patients, neutropenia--four (80%), thrombocytopenia--one (20%) and anemia--one (20%). Non-hematological toxicity was negligible. At follow-up, four (80%) patients had died of disease and one (20%) was alive with disease.. Although the combination of doxorubicin and ifosfamide has certain activity in advanced/recurrent uterine sarcomas, the toxicity is of much concern and the results of treatment in terms of response duration and survival are poor.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Protective Agents; Retrospective Studies; Sarcoma; Treatment Outcome; 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

The purpose of this study was to evaluate the activity of ifosfamide (isophosphamide) in patients with advanced or recurrent leiomyosarcoma not previously exposed to chemotherapy.. This is a phase II groupwide study of the Gynecologic Oncology Group. Thirty-five patients were treated with ifosfamide 1.5 gm/m2 daily intravenously for 5 days with mesna (mercaptoethane sodium sulfonate). Fifty-six patients had received prior abdominal hysterectomy and 15 prior radiotherapy. The dose was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy.. Gynecologic Oncology Group grade III or IV granulocytopenia occurred in 4 (11%) patients, and none had grade IV thrombocytopenia. One (2.8%) patient had grade IV neurotoxicity. Partial responses were observed in 6 of 35 (17.2%) patients. The 95% confidence interval for response was 6.6% to 33.7%.. These results indicate that ifosfamide has modest activity in patients with advanced or recurrent leiomyosarcomas of the uterus.

Topics: Adult; Aged; Agranulocytosis; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Remission Induction; Uterine Neoplasms

Uterine papillary serous carcinoma (UPSC) is a recently recognized histologic variant of endometrial carcinoma with an aggressive clinical course. This study reviews 7 patients with the diagnosis of UPSC treated at the National Kokura Hospital between 1987 and 1989. The mean age was 60 years. Clinically, 4 patients presented as Stage I, one as Stage II, one as Stage III, and one as Stage IV. Surgery upstaged 28.7% (2/7) of these patients. All 7 patients underwent a staging laparotomy followed by chemotherapy. Deep myometrial invasion was found in 5/7 (72%) of the specimens. Four of these 5 specimens demonstrated up to the uterine serosa. Lymph nodal involvement was observed in 1/4 (25%) of the specimens. Furthermore, positive peritoneal washings were obtained in 4/7 (57%) of the specimens. All patients received an adjuvant combination chemotherapy with cisplatin 50 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1, and ifosfamide 1.0 g/m2 on day 1 to day 5 (PAI). Recurrence and relapse of the disease developed in the 2 patients within 6 months. Two patients had a negative second look operation with no evidence of disease (NED) at 18 months after the initial treatment. Serial determination of the serum CA125 was seen to have great value in monitoring treatment in 4 patients. However, additional accrual and follow-up are needed to determine whether or not PAI therapy has an impact on this disease.

Topics: Aged; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Peptides; Tissue Polypeptide Antigen; Uterine Neoplasms

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Drug Evaluation; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Middle Aged; Neoplasms, Germ Cell and Embryonal; Organoplatinum Compounds; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Female; Humans; Ifosfamide; Leukocyte Count; Mesna; Middle Aged; Neoplasms, Germ Cell and Embryonal; Platelet Count; Time Factors; Uterine Neoplasms

Ifosfamide and mesna were administered to 77 patients with advanced malignancies. Seven (9%) experienced a severe but reversible encephalopathy. In 56% of patients in whom EEG data was available, characteristic changes were seen with or without mild clinical toxicity. Discriminant analysis identified low serum albumin concentration, high serum creatinine concentration and the presence of pelvic disease as variables which predispose patients to the development of severe encephalopathy. A nomogram has been constructed which can be used to determine the probability that an individual patient may be given ifosfamide and mesna safely. This has important implications for the clinical use of a highly active chemotherapy regimen.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Electroencephalography; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Soft Tissue Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Cyclophosphamide; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Uterine Neoplasms