mesna and Ovarian-Neoplasms

The patient presented in this case report was a 45-year-old female, with a Stage IIIA ovarian angiosarcoma combined with mature teratoma, that underwent debulking surgery and achieved complete remission for 11 months after six cycles of MAID chemotherapy (mesna, adriamycin/doxorubicin, ifosfamide, and dacarbazine). Thereafter, she had tumor recurrence with peritoneal seeding and massive pleural effusion; hence she received chemotherapy again. Although she had been undergoing a series of chemotherapies, the tumor continued to progress. Hence, she refused further chemotherapy since September 2012. Unfortunately, she passed away in January 2013 due to severe dyspnea with wide spread tumor progression. She had the longest survival period (31 months) and complete remission period than the other advanced primary ovarian angiosarcoma cases ever reported in the literature.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Hemangiosarcoma; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms

Ifosfamide is a cyclophosphamide analogue synthesized in the 1960s with antineoplastic activity demonstrated in early broad-ranging phase I studies conducted in Germany in the 1970s. Because of significant urothelial toxicity, phase II studies in ovarian cancer in this country were delayed until the urinary epithelial protector mesna became available in 1985. Since that time, two well-executed prospective trials have shown that this agent produces measurable responses in about 20% of women with ovarian epithelial cancer recurring after primary chemotherapy and in 12% of those with tumors refractory to first-line therapy with regimens including cisplatin. Toxicity includes moderate to severe hematologic toxicity, renal dysfunction which is usually reversible, and CNS abnormalities including lethargy, somnolence, and disorientation. The risk of toxicity may be increased in patients with compromised hepatic or renal function and in those with hydronephrosis or hypoalbuminemia.

Topics: Carcinoma; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Ifosfamide; Mesna; Ovarian Neoplasms; Urologic Diseases

To evaluate the efficacy and toxicity of cisplatin and ifosfamide in the treatment of patients with malignant mixed mesodermal tumor (MMMT) of the ovary.. Ten patients with histologically confirmed primary MMMT of the ovary diagnosed between 1993 and 2001 were enrolled in the study. Treatment consisted of cisplatin 75 mg/m2 on day 1, followed by ifosfamide 2.0 g/m2 over 24 h on days 1, 2 and 3. Mesna, 400 mg/m2, was given IV immediately prior to and 4 and 8 h after the start of each ifosfamide infusion. Chemotherapy was repeated on a 28-day cycle if blood counts permitted. Standard response criteria were used. Nine patients were evaluable for response.. Eight of the nine patients responded to therapy, with 7 complete responses (78%) and 1 partial response. Seven of the eight responders (87.5%) eventually recurred. The median progression-free survival was 10 months (range 0-94.4 months). The median overall survival was 17.1 months (range 8-125.5 months). One patient remained free of disease 94.4 months after diagnosis, and one patient remained alive with recurrence 125.5 months following diagnosis. There were 13 grade 3 toxicities and 4 grade 4 toxicities. Four patients had grade 4 and three had grade 3 neutropenia, all of which required dose reductions.. The combination of cisplatin and ifosfamide/mesna demonstrated activity against MMMT of the ovary. Response durations were short, however, and the regimen was associated with significant toxicity. Novel agents with activity against MMMT of the ovary and acceptable toxicity are needed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Humans; Ifosfamide; Mesna; Middle Aged; Mixed Tumor, Mesodermal; Neoplasm Staging; Ovarian Neoplasms; Pilot Projects

Salvage chemotherapy in advanced ovarian cancer is not yet standardized.. Twenty-one consecutive patients progressing on or relapsing after previous platinum-containing treatment were eligible for treatment with ifosfamide 5 g/m(2) infused over a 24-hour period every 3 weeks in a Phase II trial. After an initial bolus of 1 g/m(2) of mesna, mesna was applied at a dosage of 5 g/m(2) concomitantly with ifosfamide followed by additional dosages of 200 mg 3 times at 4-hour intervals after termination of the ifosfamide infusion.. The rate of objective responses was 19 percent, with a 95%CI [5.45-41.91 percent]. One patient achieved a pathologic complete remission (pCR) and 3 patients a clinical partial remission (PR). Median time-to-progression was 3 months. One patient was a long-term survivor. Main toxicities according to NCI-CTC included Grade 4 neurotoxicity in one patient, Grade 3 gastrointestinal toxicity in 5 patients, Grade 3 infection in one patient, and Grade 3 and 4 leucopenia in 6 and 2 patients, respectively.. Monotherapy with ifosfamide represents an active regimen for salvage chemotherapy in advanced ovarian cancer patients progressing on or relapsing after previous platinum-pretreatment, even yielding a long-term surivor.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Platinum Compounds; Protective Agents; Salvage Therapy; Survival Analysis; Treatment Outcome

From August 1995 to December 1997, 15 patients with stage III-IV ovarian cancer were treated with outpatient intensive chemotherapy with G-CSF and stem cell support. The first cycle consisted of cyclophophamide IV 6 g/m(2); second, third, fourth and fifth paclitaxel 250 mg/m(2) and the sixth and seventh carboplatin AUC 18. CD34(+) cells were collected after the first cycle and reinfused after completion of cycles 6 and 7. Fourteen patients had stage IIIc and one patient had stage IV disease with liver metastases. All patients underwent laparotomy to maximize tumor debulking. This was optimal in eight patients and suboptimal in seven patients. Second-look surgery was performed in 14 patients. All patients had macroscopic complete responses and 10 patients had complete histologic response. Median follow-up was 48 months (range, 20 to 62). Twelve patients had further progression at a median of 27 months (range, 9 to 42) and nine are alive, three without evidence of disease progression. This pilot study shows that dose-dense chemotherapy with paclitaxel and carboplatin is associated with low toxicity and may improve the outcome of patients with poor prognosis ovarian cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Disease-Free Survival; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Life Tables; Mesna; Middle Aged; Ovarian Neoplasms; Paclitaxel; Peripheral Blood Stem Cell Transplantation; Peripheral Nervous System Diseases; Pilot Projects; Prognosis; Recombinant Proteins; Remission Induction; Survival Analysis; Treatment Outcome

The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer.. Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for the first 14 patients.. Between February 1997 and December 1998, 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed.. This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Diseases; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neutropenia; Organoplatinum Compounds; Ovarian Neoplasms; Paclitaxel; Vinblastine; Vinorelbine

The combination of paclitaxel with a platinum analogue is the preferred chemotherapy regimen in the treatment of advanced epithelial ovarian carcinoma. The alkylating agent ifosfamide has shown activity in refractory or recurrent ovarian cancer. We conducted a Phase II study with the combination of ifosfamide, paclitaxel, and cisplatin for the treatment of newly diagnosed patients with advanced, suboptimally debulked ovarian carcinoma.. Thirty-five consecutive patients with advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage III or IV) and residual disease larger than 2 cm after staging laparotomy and cytoreductive surgery were treated with paclitaxel, 175 mg/m(2), as a 3-hour intravenous infusion on Day 1, cisplatin 75 mg/m(2) intravenously over 2 hours on Day 2, and ifosfamide 1500 mg/m(2) intravenously over 1 hour on Days 1-3 (with sodium 2-mercaptoethane sulfonate [MESNA] uroprotection). Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was given at a dose of 5 microg/kg/day on Days 7-11.. Among 26 patients with measurable disease, 22 (85%) achieved an objective response including 15 complete and 7 partial responses. With a minimum follow-up of 46 months, the median overall survival was 52.8 months (range, 5.3-56.6+ mos), whereas the median time to progression for all patients was 22.2 months. The median remission duration for women with measurable disease who responded to treatment was 12.6 months. The treatment was tolerated relatively well without toxic deaths; the most common toxicity was Grade 3 or 4 neutropenia that occurred in 42% of patients. Significant peripheral neuropathy (Grade 2 or higher) developed in 35% of patients.. The combination of ifosfamide, paclitaxel, and cisplatin is a well-tolerated outpatient regimen with significant activity in the treatment of newly diagnosed FIGO Stage III or IV epithelial ovarian carcinoma. Further evaluation is justified to clearly define the role of ifosfamide as an additional agent to the current platinum and paclitaxel regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Cisplatin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Survival Analysis

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Component Removal; Carcinoma; Combined Modality Therapy; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Transplantation, Autologous

In an effort to use antineoplastic drug combinations which are active in platinum resistant ovarian cancer or which can induce a second response after a platinum first-line treatment, we conducted a study on 30 ovarian cancer patients previously treated with carboplatin plus cyclophosphamide who were given ifosfamide 5 g/m2 i.v. divided over days 1 to 3 plus mesma combined with cisplatin 100 mg/m2 i.v. divided over days 1 to 3 every 4 weeks as second-line treatment. Eight patients had never entered remission with first-line chemotherapy while 22 patients had tumor recurrence within 6 to 18 months after the end of chemotherapy and their tumors were considered potentially platinum sensitive. Responding patients received 6 courses while palliative treatment for nonresponders was provided. Of the 22 patients with tumor recurrence, 8 patients responded with one partial response (PR) and 7 complete clinical responses (CCR). Two out of the 8 patients with platinum resistant disease demonstrated short lasting PR. Seven patients with CCR underwent second-look operation and in two a pathological CR was documented. Median time to progression was 6 mo (4-12). The median overall survival was 12 mo (4-20). Myelotoxicity despite G-CSF administration was significant with grade 4 leukopenia in 40% and grade 3 thrombocytopenia in 20% of patients. Central nervous system (CNS) toxicity was significant with 30% somnolence, 20% disorientation and an episode of grand-mal epilepsy ascribed to ifosfamide. With a 33% response rate the combination is as effective as new agents employed in relapsed ovarian cancer. Platinum-refractory disease may respond to a lesser degree. The most important determinant of response was the progression-free interval from first-line chemotherapy. Whether patients recurring after carboplatin plus cyclophosphamide have a greater chance to respond to cisplatin plus ifosfamide or vice-versa cannot be supported by the current data and therefore randomized studies should be performed to this end.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Cyclophosphamide; Disease Progression; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Palliative Care; Prognosis; Survival Analysis

Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination.. Patients with refractory, incurable solid tumors were entered on a 5-step Phase I trial of ifosfamide, given in doses of 2-3 g/m2 intravenous (i.v.) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m2 i.v. by continuous infusion over 24 hours. Paclitaxel was given after the first dose of ifosfamide on Day 1.. Twenty-three patients were treated, and the maximum tolerated dose was the highest planned dose level of the trial: ifosfamide, 3 g/m2/day i.v. for 3 days, and paclitaxel, 190 mg/m2 i.v. over 24 hours. Hematologic toxicity was not dose-limiting, and although neutropenia occurred, it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patients treated at the highest dose level, only 1 of 50 courses of therapy resulted in hospitalization for neutropenia and fever. Nonhematologic toxicity also was not severe and no significant neuropathy occurred. Although patients entered into the study were heavily pretreated, responses were observed, particularly in patients with breast or ovarian carcinoma.. Ifosfamide and paclitaxel can be administered safely in the doses used in this study and there are indications of significant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients with breast and ovarian carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colonic Neoplasms; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasms; Neutropenia; Ovarian Neoplasms; Paclitaxel

The addition of stem cell factor (SCF) to G-CSF and chemotherapy results in a dose-dependent, significantly increased mobilisation of peripheral blood progenitor cells compared with the use of chemotherapy and G-CSF alone. The enhanced mobilisation may benefit patients in several ways. Firstly, in clinical settings where currently multiple aphereses are having to be performed to obtain a specified target number of cells, the addition of SCF may lead to a reduction in this number. Alternatively, when only a single apheresis is currently being performed to obtain sufficient cells then the addition of SCF to the mobilisation regimen would allow between 5- and 8-fold reduction in the volume of blood required to be processed during the apheresis procedure to obtain a specified target of GM-CFC, CD34+ cells and LTC-IC for those receiving the highest dose of SCF (20 microg/kg) plus G-CSF following chemotherapy compared with those patients receiving G-CSF alone following chemotherapy. The increased mobilisation resulting from the addition of SCF to the regimen makes feasible the use of whole blood aliquots to support dose-intensive therapy. We have calculated that in patients mobilised using cyclophosphamide 3 g/m2, SCF 20 microg/kg and G-CSF 5 microg/kg a median 512 ml aliquot of whole blood would contain 2 x 10(6)/kg CD34+ cells and over 3.7 x 10(5)/kg GM-CFC. This aliquot would be sufficient to rescue the patient following a myeloablative therapy. Significantly, because less individual variation was seen after the administration of SCF the patient who showed the worst mobilisation in that group would have the usually required content of 2 x 10(6) CD34+ cells/kg and 1 x 10(5) GM-CFC/kg in only 731 ml of blood.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Blood Component Removal; Cyclophosphamide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Mesna; Middle Aged; Ovarian Neoplasms; Stem Cell Factor

Ifosfamide (IFX) and mitoxantrone (MXN) have been found to be effective against advanced epithelial ovarian cancer. The combination of these two agents has not yet been tested in this setting but seems to be rational, given the different action mechanisms of these drugs and their not completely overlapping side effects. Between June 1987 and November 1991, 37 patients with advanced ovarian carcinoma recurrent or refractory to primary cisplatin-based chemotherapy entered the study. Therapy consisted of MXN, given i.v. at 10 mg/m2 on day 1 and IFX given i.v. at 2,000 mg/m2 per day on days 1-3 with mesna. The cycles were repeated every 3 weeks. Four patients achieved a complete remission and three achieved a partial remission, for response rates of 18.9% [95% confidence interval (CI) 6.3-31.5%] in the whole sample and 38.8% (95% CI 16.3-61.3%) in the subset of 18 patients responding to first-line cisplatin. No response was obtained in the remaining patients, whose disease was refractory to primary platinum-based chemotherapy. Clinically significant toxicity (WHO grades 3-4) included leukopenia in 46% of the patients and anemia in 32.5%. The non-hematologic toxicity was mild, except for reversible alopecia (57%) and nausea and vomiting (48.5%). This regimen seems attractive for patients who have either failed or not received platinum retreatment, especially when limiting neurotoxicity occurs. Further studies are warranted to establish the relative impact of both of these agents.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Expectorants; Female; Humans; Ifosfamide; Infusions, Intravenous; Longitudinal Studies; Mesna; Middle Aged; Mitoxantrone; Ovarian Neoplasms; Salvage Therapy; World Health Organization

Long-term culture-initiating cells (LTC-IC) are arguably the most primitive human hematopoietic cells detectable by in vitro functional assays. We have investigated the mobilization of these cells into the blood of patients with ovarian carcinoma randomized to receive granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg) plus different doses of stem cell factor (SCF; c-kit ligand) after chemotherapy or G-CSF alone after chemotherapy. We have shown a significant SCF dose response for the mobilization of LTC-IC, with a 5.8-fold increase in LTC-IC mobilization in those patients receiving chemotherapy, G-CSF, and 20 micrograms/kg of SCF, the highest dose used, compared with the patients receiving chemotherapy and G-CSF alone. We have shown a threefold increase in CD34+ cells and up to a 64-fold increase in CD34+/33- cells was seen in patients treated with chemotherapy, G-CSF, and 20 micrograms/kg of SCF compared with those patients treated with chemotherapy and G-CSF alone. However, significant numbers of CD34+/38- cells were only found in the patients receiving 20 micrograms/kg of SCF as part of their mobilization regimen. Patients receiving chemotherapy plus G-CSF and SCF have enhanced mobilization of primitive cells and of the more committed progenitor cells compared with those patients receiving chemotherapy followed by G-CSF alone.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Component Removal; Carcinoma; Cell Count; Clone Cells; Cohort Studies; Cyclophosphamide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Infusions, Intravenous; Mesna; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Stem Cell Factor; Time Factors

Continuous 24-hr infusion of ifosfamide (IFX) with mesna was studied in 19 patients with advanced epithelial ovarian cancer refractory to or recurrent after platinum-containing chemotherapy. The patients received IFX 5 g/m2 as a 24-hr i.v. infusion. Mesna (total dose 8 g/m2) was given i.v. 3 hr before, together with, and 0 and 6 hr after IFX infusion, respectively. Cytotoxic therapy was repeated every 4 weeks. Of 19 evaluable patients, none achieved a complete response, 2 showed a partial response, and 8 had stable disease. Median survival for all patients was 6 months, and median time to progression was 4 months. Toxicity was moderate. Leucopenia WHO grade III-IV was observed in 3 patients. Thrombocytopenia WHO grade III-IV was not observed. Nausea/vomiting WHO grade III-IV occurred in 8 patients. One patient experienced mild reversible confusion. No patients had macro-or microscopic hematuria and there was no deterioration of renal function. We conclude that IFX given as a 24-hr infusion is moderately well tolerated, but has only limited activity in patients with ovarian cancer refractory to or relapsing after prior platinum-containing chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Ifosfamide; Infusions, Intravenous; Mesna; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Platinum Compounds; Remission Induction; Salvage Therapy; Survival Analysis

A phase II trial of ifosfamide and mesna in women with mixed mesodermal tumors of the ovary who had previously received platinum-containing chemotherapy was conducted by the Gynecologic Oncology Group (GOG). The starting dose of ifosfamide was 1.2 g/m2 daily iv for 5 days. Mesna was given intravenously with and at 4 and 8 hr following the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. Thirty-two patients were placed on the study; 31 were evaluable for toxicity and 28 for response. Twenty-seven patients (87.1%) had previously undergone surgery and three (9.3%) had received radiotherapy before this trial. GOG grade 3 or 4 granulocytopenia occurred in 11 (35.5%) patients, and one (3.2%) developed grade 4 thrombocytopenia. Two patients (6.4%) had grade 3 neurotoxicity. A complete response was observed in one patient (3.6%) and partial responses in four patients (14.3%) for a total response rate of 17.9% (95% confidence interval = 6.1-36.9%). In conclusion, ifosfamide has activity in previously mixed mesodermal tumors of the ovary.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Ifosfamide; Mesna; Middle Aged; Mixed Tumor, Mesodermal; Organoplatinum Compounds; Ovarian Neoplasms; Time Factors

Forty-five patients with progressive or recurrent ovarian carcinoma received cisplatin, etoposide, and ifosfamide as salvage chemotherapy. The primary purpose of this trial was to evaluate if etoposide and ifosfamide added to cisplatin was effective second line therapy in the 20 patients with progressive or recurrent ovarian cancer after first line cisplatin-based chemotherapy. The overall response in the 20 patients was 20%, all of which were complete responses. However, responses were seen only in patients who had previously responded to first line cisplatin-based chemotherapy and then developed recurrent cancer, whereas none of the patients whose cancer progressed during first line cisplatin-based chemotherapy responded. The addition of etoposide and ifosfamide to cisplatin as second line therapy does not potentiate cisplatin in patients demonstrating first line cisplatin resistance and most likely does not contribute to the second line responses in those patients who demonstrated first line cisplatin sensitivity. This combination is also ineffective as third, forth, fifth or sixth line salvage chemotherapy with a response rate of only 8%.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Infusions, Intravenous; Mesna; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Salvage Therapy; Treatment Outcome

There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting.. Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities.. Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program.. Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Topics: Acute Kidney Injury; Adult; Aged; Carcinoma; Drug Evaluation; Drug Resistance; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Platinum

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

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.

Topics: Carcinoma; Drug Evaluation; Female; Humans; Ifosfamide; Leukocyte Count; Mercaptoethanol; Mesna; Multicenter Studies as Topic; Ovarian Neoplasms; Platelet Count

High-dose alkylating chemotherapy with cyclophosphamide (4000 or 6000 mg/m2) and thiotepa (320 or 480 mg/m2) has commonly been administered in a fractionated regimen over 4 days. A simplified unfractionated regimen would be preferable, especially because cyclophosphamide and thiotepa have been shown to influence the metabolism of each other. However, altering a dose regimen can have a profound effect on the pharmacokinetics of the compounds involved. The aim of this study was to investigate the effect of altering the fractionated administration schedule of the CTC regimen on cyclophosphamide and thiotepa pharmacokinetics. Plasma samples were collected from 124 patients who received a fractionated tiny CTC or CTC regimen of cyclophosphamide (1000 or 1500 mg m(-2) d(-1)), thiotepa (40 or 60 mg/m2 twice daily), and carboplatin (267 or 400 mg m(-2) day(-1)) for 4 days, and 16 patients who received an unfractionated mini CTC regimen of cyclophosphamide (3000 mg/m2 at day 1), carboplatin (400 mg/m2 at days 1 and 2), and thiotepa (250 mg/m2 at day 2). Plasma concentrations of cyclophosphamide and 4-hydroxycyclophosphamide were determined using high-performance liquid chromatography coupled with tandem mass spectrometric detection; plasma concentrations of thiotepa and tepa were determined using gas chromatography. Pharmacokinetics of cyclophosphamide and thiotepa were assessed using nonlinear mixed-effect modeling. The study showed that alteration of a fractionated high-dose regimen into a simplified unfractionated regimen resulted in saturation of thiotepa elimination, with a Vmax of 212 (+/-58) micromol/h and a Km of 13.7 (+/-5.9) microM. This resulted in an increased dose-corrected exposure to thiotepa (13%) and decreased dose-corrected exposure to its metabolite tepa (21%). Elimination of cyclophosphamide was not shown to be saturable. Dose-corrected exposures to cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide were comparable in both regimens. Because the simplified unfractionated mini CTC regimen was more patient-friendly and because overall dose-corrected exposures to cyclophosphamide and thiotepa were not affected to a relevant extent, our data suggest that this unfractionated regimen can be used safely in future studies.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biotransformation; Breast Neoplasms; Chromatography, Gas; Chromatography, High Pressure Liquid; Cyclophosphamide; Expectorants; Female; Forecasting; Humans; Infusions, Intravenous; Male; Mesna; Models, Statistical; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Testicular Neoplasms; Thiotepa

There are 20 documented cases of primary ovarian angiosarcoma. Most patients present with metastatic disease and respond poorly to chemotherapy. There is little information available to counsel early-staged patients on the need for or efficacy of adjuvant chemotherapy.. We present a case of Stage Ic primary ovarian angiosarcoma treated with 3 cycles of adjuvant MAID chemotherapy. The patient is without evidence of disease 10 months post-operatively.. A review of the literature indicates a potential role for MAID chemotherapy in the treatment of ovarian angiosarcomas. Detection of Stage I disease appears to confer a better prognosis regardless of the utilization of adjuvant chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dacarbazine; Doxorubicin; Female; Hemangiosarcoma; Humans; Ifosfamide; Mesna; Neoplasm Staging; Ovarian Neoplasms

BNP7787 (2',2'-dithio-bis-ethane sulphonate sodium), a water-soluble disulphide, is chemically and mechanistically different from other sulphur-containing chemoprotective agents. Presently, BNP7787 is under investigation for its protective properties with regard to the side-effects of platinum compounds. In this study, we evaluated BNP7787, mesna and amifostine for their effects on the antitumour activity of platinum compounds. Continuous exposure to BNP7787 did not affect the antiproliferative effects of cisplatin or carboplatin, but the efficacy of both compounds was reduced in the presence of mesna in vitro in two human ovarian cancer cell lines. BNP7787 or amifostine combined with cisplatin or carboplatin given in standard schedules for the treatment of nude mice bearing well-established OVCAR-3 xenografts did not interfere with platinum-induced inhibition of tumour growth. Of interest, BNP7787 or amifostine co-administered with carboplatin was significantly more effective than carboplatin alone (P<0.01). In the presence of amifostine, doses of cisplatin and carboplatin could be safely increased by factors of 1.6 and 1.5, respectively. Unlike in a previous study of BNP7787 in tumour-bearing rats, BNP7787 did not protect against additional weight loss following treatment with higher doses of cisplatin in OVCAR-3-bearing mice. Pharmacokinetics of (mixed) disulphides including BNP7787 and extractable mesna in deproteinised plasma revealed a rapid disappearance of BNP7787 and an AUC(5-60) value of mesna 9-fold lower than that calculated after an equivalent dose of mesna by weight. We can conclude that BNP7787 does not interfere with the antitumour activity of platinum compounds in vitro and in vivo. Clinical trials are underway to evaluate the protection of normal tissues by BNP7787 when combined with cisplatin.

Topics: Amifostine; Animals; Antineoplastic Agents; Carboplatin; Cell Division; Cisplatin; Drug Interactions; Female; Humans; Lethal Dose 50; Mesna; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Protective Agents; Radiation-Protective Agents; Transplantation, Heterologous; Weight Loss

Topics: Antineoplastic Agents; Brenner Tumor; Carcinoma, Transitional Cell; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian 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

To evaluate the activity of two cycles of high-dose ifosfamide, carboplatin, and etoposide (ICE) with autologous hematopoietic progenitor cell support (aHPCS) in patients with poor-prognosis, chemotherapeutically sensitive germ cell cancer.. Twenty patients with germ cell tumor who had persistent disease or relapse from standard-risk or high-risk presentation were entered on this pilot study. The entry criteria included relapsed gonadal and extragonadal germ cell cancer unlikely to be cured by standard salvage therapy but without proven refractoriness to chemotherapy. Treatment consisted of two cycles of ICE chemotherapy with mesna uroprotection and aHPCS. On the first cycle, ifosfamide (IFX), 2 gm/m2; carboplatin, 400 mg/m2; and etoposide, 20 mg/kg, were administered on days -6, -5, and -4. On the second cycle, the doses and schedule of carboplatin and etoposide were identical, and patients with normal renal function received additional IFX, 2 g/m2 on day -3 and 1 g/ m2 on day -2. Mesna, 600 mg/m2 every 6 hours, was given until 24 hours following the final dose of IFX on each cycle, and autologous bone marrow and/or peripheral stem-cells were infused on day 0.. All twenty patients are assessable for toxicity and current disease status. Two patients received only one cycle of therapy, one because of the development of active hepatitis C following cycle 1, and one because of renal insufficiency. No patient died as a result of protocol therapy, and no patient developed debilitating peripheral neuropathy, symptomatic hearing loss, or severe renal insufficiency requiring dialysis. The median time to recovery of > or = 500 neutrophils/microL and platelets > or = 50,000/microL was day +11 and day +15, respectively. The median maximum creatinine was 1.6 mg/dL on each treatment cycle, and there was no other significant organ toxicity. With a median follow-up of 45 months, nine patients are alive and disease-free following protocol chemotherapy. One patient with embryonal cancer developed progressive pulmonary metastases 3 months after completing high-dose therapy, underwent complete resection of lung metastases, and remains disease-free at 63+ months. Eight patients are continuously disease free at 23+ to 70+ months after protocol therapy. Eleven patients died of progressive disease between 4 and 23 months following completion of treatment.. These results compare favorably to other studies in similarly selected patients undergoing salvage therapy with one or two cycles of chemotherapy containing high-dose carboplatin and etoposide with or without cyclophosphamide (CTX) or IFX. The excellent safety and tolerability profile of this regimen and its encouraging activity in poor-prognosis patients make it worthy of further study as part of initial therapy in randomized protocols for high-risk disease and early in the treatment of relapsed germ cell cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Etoposide; Female; Follow-Up Studies; Germinoma; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Male; Mediastinal Neoplasms; Mesna; Middle Aged; Ovarian Neoplasms; Pilot Projects; Retroperitoneal Neoplasms; Testicular 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

20 patients with ovarian carcinoma whose disease had relapsed (1-42 months, median 4 months) after showing either response or stable disease to carboplatin, were treated with ifosfamide (5 g/m2 intravenously over 24 h, day 1) and carboplatin (200 mg/m2 intravenously day 2) as second-line treatment. The mean number of treatment cycles was 3.5 (range 1-6). The major toxicities were thrombocytopenia (WHO grade 3/4, 25%), neutropenia (WHO grade 3/4, 40%) and encephalopathy (WHO grade 3/4, 15%). Overall response rate was 15% [complete response, 0; partial response, 3 (15%); no change, 5 (25%) and progressive disease, 12 (60%)]. The median survival from the date of second-line treatment was 7 months. This combination offers no advantage over either agent used alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Palliative Care

Twenty-one evaluable patients with FIGO stages II-IV epithelial ovarian cancer, median age 57 (range 47-75 years), were treated with ifosfamide (IF), 3 g/m2 diluted in 500 ml saline solution, 8 hour intravenous (i.v.) infusion on days 1-5; mesna 20% of IF dose, i.v. bolus injection, was given at hours 0 and 4; mesna 40% of IF dose by oral route at hours 8 and 12, days 1-5; plus cisplatin 20 mg/m2 diluted in 500 ml saline solution, 2 hour i.v. infusion, days 1-5. Cycles were repeated every 4 weeks. All patients had metastatic lesions (mesentery, pleura, colon, cervix, abdominal wall, lung, liver, bladder, and nodes). Toxicity ranged from mild to moderate. All patients experienced alopecia, nausea, and vomiting. Neutropenia and anemia ranged from mild to moderate. One patient experienced mild brain confusion and two patients microscopic hematuria. Ten clinically complete responses (47%) and five clinically partial responses (23%) were registered, for an overall 70% objective response. However, after a second look performance in 10 patients with clinically complete response, six of 10 patients showed a pathological complete response and four showed pathological partial response. The median duration of complete response is about 33 months, and median partial response duration is 14 months. Although the numbers are small, these data indicate that combination chemotherapy with high dose ifosfamide/mesna plus cisplatin may be an active treatment for advanced ovarian carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Survival Rate

The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapy-resistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5-41 months). No patients who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4-12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2-13+ months) and that in the remaining group was 13 months (ranges 3(+)-24 months) (P less than 0.05). This treatment was moderately well tolerated. Grade 3 nausea and vomiting occurred in 27% of cycles and grade 3-4 leukopenia was observed in 47%, but thrombocytopenia was hardly ever found. In eight patients there was a deterioration of renal function. Among a total of 131 cycles, the dose was reduced for only 9 due to myelotoxicity and for 3 due to nephrotoxicity. IFX seems to be active only in patients who have relapsed after responding to previous cytotoxic treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Ifosfamide; Infusions, Intravenous; Mercaptoethanol; Mesna; Neoplasm Recurrence, Local; Ovarian Neoplasms

Starting in July 1985, the Gynecologic Oncology Group conducted a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received 1.5 g/m2 i.v. ifosfamide daily for 5 days. Mesna was given i.v. q4h x 3 following ifosfamide; each dose was 20% of the daily ifosfamide dose. All patients with ovarian and 87% of those with cervical cancer had previously undergone 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 daily in all patients who had received prior chemo- or radiotherapy. In epithelial ovarian carcinoma, responses were observed in 8 (20.0%) of 41 evaluable patients, with 3 (7.0%) complete responses. Response duration was 2.1-20.3+ months, with a median of 6.9+ months. In squamous-cell carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients showed partial responses of 1.8, 2.2, and 3.1 months' duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) achieved complete and 3 (11.5%) showed partial responses, for an overall response rate of 30.7%. Response duration was 1.4(+)-8.6 months, with a median of 3.8 months. Toxicity included two deaths due to 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 Agents; Carcinoma; Drug Evaluation; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Middle Aged; Ovarian Neoplasms; Sarcoma; Uterine Cervical Neoplasms

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Drug Evaluation; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Ovarian Neoplasms

Fifty patients with histologically confirmed advanced malignancies were treated with ifosfamide and mesna plus other cytostatics. The other cytostatic drugs added to the treatment regimen were cisplatin (36 pts), etoposide (31 pts) and doxorubicin (20 pts). Among previously untreated patients objective response was documented in 12 of 19 pts with ovarian cancer, 9 of 14 with small cell cancer of the lung and in all 3 pts with Ewing's sarcoma. Among patients with disease refractory to prior cytostatic treatment, objective response was documented in 8 of 9 with testicular cancer, 1 of 3 with high grade lymphoma and 0 of 2 with osteosarcoma. Side-effects due to the combination of ifosfamide plus mesna and other cytostatics were acceptable. No life-threatening or lethal toxicities occurred. Most commonly encountered toxicities were leukopenia (64%), nausea and vomiting (84%), alopecia (63%), CNS toxicity (30%) and renal toxicity (12%).

Topics: Adolescent; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Etoposide; Female; Humans; Ifosfamide; Leukopenia; Lung Neoplasms; Male; Mesna; Middle Aged; Nausea; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Vomiting

A 62-year-old woman developed subacute renal failure after the repeated administration of ifosfamide (IFX), despite its combination with continuous sodium 2-mercaptoethane sulfonate (mesna) infusion. Biopsy findings, the possible underlying mechanism, and the existing literature are discussed.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma; Dose-Response Relationship, Drug; Female; Humans; Ifosfamide; Kidney; Mercaptoethanol; Mesna; Middle Aged; Ovarian 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

Topics: Adult; Aged; Carcinoma, Bronchogenic; Female; Hematuria; Humans; Ifosfamide; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Middle Aged; Neoplasms; Ovarian Neoplasms; Testicular Neoplasms

In an open multicenter phase III trial, prophylaxis of the urinary tract with sodium 2-mercaptoethanesulfonate (Mesnum) was carried out in 242 patients treated with oxazaphosphorines for various malignant tumors. Under the protection of Mesnum 29 patients were treated with cyclophosphamide (Endoxan), 195 with ifosfamide (Holoxan) and 8 with trofosfamide (Ixoten). Other cytostatics were also used (polychemotherapy) in 92 cases. On administration of Mesnum, 7 macrohematurias reappeared, only 3 of them however with correct application, and 22 microhematurias, 12 of them with correct application. Cylindrurias were re-established in 3 patients. In Mesnum we have a compound which can control the urotoxicity ("uroprotector") of oxazaphosphorines which limits their therapeutic use.

Topics: Adolescent; Adult; Aged; Bronchial Neoplasms; Child; Cyclophosphamide; Female; Gastrointestinal Diseases; Hematuria; Humans; Ifosfamide; Male; Mercaptoethanol; Mesna; Middle Aged; Ovarian Neoplasms; Phosphoramide Mustards; Testicular Neoplasms