mesna and Central-Nervous-System-Diseases

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

In a phase II trial of ifosfamide 2 g/m2 days 1 to 4 with mesna uroprotection in 124 patients who had previously failed treatment for sarcomas, 3% achieved a complete response (CR), and 18% had a CR or partial response (PR). In the subset of patients with soft-tissue sarcomas, the response rate for the 64 patients who received bolus administration was 26% compared with 9% for the 60 patients who received a continuous infusion (Cl) schedule (P = .03). When mesna was unavailable, the incidence of hematuria was significant in patients, with three of four patients affected. Microscopic hematuria was uncommon in patients receiving mesna. Hematuria in the group as a whole was not associated with prior treatment with cyclophosphamide, pelvic radiotherapy, age, or a bolus versus Cl schedule. Thus, this and other studies confirm that ifosfamide is active in failed sarcomas. In sequential phase I/II trials, 111 patients who were previously untreated for metastatic or inoperable sarcomas received doxorubicin, ifosfamide, dacarbazine at doses of 60, 7,500, and 900 mg/m2, respectively, by Cl over 72 hours; myelosuppression was dose-limiting. Eleven patients (10%) achieved CRs, with an overall response rate of 47%. Most responses (approximately 70%) were observed within two cycles, and median times to progression were 10 and 9 months for CR and PR, respectively. Following CR, two patients remained disease-free at 32 and 16 months. Of 15 additional patients rendered disease-free with surgery following at least a minor response to chemotherapy, two remained disease-free at 30 and 18 months with no further therapy. Central nervous system (CNS) metastases developed in 11 patients, all of whom had high-grade sarcomas; seven of these patients were still responding systemically (three CRs). This regimen is undergoing evaluation in a randomized trial versus doxorubicin and dacarbazine alone in untreated advanced sarcoma and is being compared with observation in the adjuvant treatment of high-grade sarcomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Central Nervous System Diseases; Child; Child, Preschool; Combined Modality Therapy; Dacarbazine; Doxorubicin; Drug Administration Schedule; Female; Heart Diseases; Humans; Ifosfamide; Lung Diseases; Male; Mesna; Middle Aged; Randomized Controlled Trials as Topic; Sarcoma; Survival Analysis; Urologic Diseases

Topics: Breast Neoplasms; Central Nervous System Diseases; Computer-Aided Design; Controlled Clinical Trials as Topic; Drug Design; Drug Interactions; Female; Humans; Mesna; Paclitaxel

Topics: Adult; Central Nervous System Diseases; Drug Administration Schedule; Drug Therapy, Combination; Humans; Ifosfamide; Infusions, Intravenous; Liver; Mesna; Middle Aged; Retrospective Studies

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Diseases; Female; Humans; Ifosfamide; Mesna; Middle Aged

Thirty patients with symptomatic, progressive squamous cell carcinoma of the uterine cervix no longer amenable to surgery or radiotherapy were entered in a phase II study of ifosfamide (IFX). Patients were treated with IFX (5 g/m2 iv given over 24 hours) and concomitant mesna (total dose, 9.2 g/m2 iv given over 36 hours) every 21 days. One complete response (duration, 10+ months) and nine partial responses were observed, with an overall median response duration of 6.5 months. The median survival of responding patients was 11 months. Objective response rates for lesions arising in previously irradiated sites (four of 22) were significantly lower than for lesions arising in nonirradiated sites (15 of 28) (P = 0.018). There were two treatment-related deaths: one due to leukopenia-associated infection in a patient with peritonitis and severe central nervous system toxicity and one due to central nervous system toxicity without complicating factors. One other patient developed severe but reversible encephalopathy. In all remaining patients hemorrhagic cystitis and hematological and gastrointestinal toxic effects were predictable and manageable. Treatment was delayed for 1 week due to toxicity on seven of 101 occasions: four of these delays were due to mild, reversible impairment of renal function and three were due to leukopenia. Complete though reversible alopecia occurred in 22 of 30 patients. The results indicate that IFX is active in cervical cancer and deserves further study in this setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Central Nervous System Diseases; Drug Evaluation; Female; Hematologic Diseases; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Nausea; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms

Ifosfamide/mesna treatment of 50 patients with pediatric malignant solid tumors was associated with the development of neurotoxic signs and symptoms in 11 of these individuals who received 29 courses of treatment. Neurologic toxicity included changes in mental status, cerebellar function, cranial nerve, and cerebellar and motor system function, including seizures. All symptoms, signs, and EEG abnormalities were transient. Some of the affected individuals failed to develop acute neurotoxic signs of symptoms when retreated with ifosfamide. A grading system for scoring these neurologic abnormalities is presented for comparison of acute neurotoxic effects of other agents. Recommendations are made regarding early termination or delay of ifosfamide/mesna treatments in the presence of significant neurotoxicity.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Diseases; Child; Child, Preschool; Electroencephalography; Female; Humans; Ifosfamide; Male; Mesna; Neoplasms; Seizures

The authors have had the opportunity to see two cases of CNS side effects of Ifosfamide-Mesna association in children. Data in the medical literature about this subject remains poor. Only a few observations are available. In the referred cases, CNS side effects (lethargy, apathy and mutism) appeared a few hours after the second day of treatment and were spontaneously reversible in a few days. After reviewing possible mechanisms of this toxicity the authors pointed out the necessity to keep this type of side effects of Ifosfamide-Mesna association in mind, and to avoid it in susceptible patients.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Central Nervous System Diseases; Child; Female; Humans; Ifosfamide; Mesna; Osteosarcoma