mesna and Drug-Hypersensitivity

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cerebellar Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Hypersensitivity; Female; Humans; Medulloblastoma; Mesna; Osteosarcoma; Protective Agents; Spinal Neoplasms

In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients.. Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v. bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration.. Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with i.v. and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels.. Paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Breast Neoplasms; Cyclophosphamide; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Equipment Failure; Erythrocyte Transfusion; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hematuria; Home Infusion Therapy; Humans; Mesna; Middle Aged; Neoplasm Metastasis; Paclitaxel

Topics: Cyclophosphamide; Drug Hypersensitivity; Humans; Mesna

Both 2-mercaptoethane sulfonate sodium (mesna) and amifostine's active metabolite WR-1065 are thiol-based cytoprotective agents that are critical components of high-dose chemotherapy regimens used to treat various cancers in both adults and children. This case report describes a patient with a supratentorial primitive neuroectodermal tumor who developed severe drug reactions to both mesna and amifostine/WR-1065, suggesting that the thiol component of these agents triggered the adverse reactions. This report highlights the clinical presentation of drug-induced hypersensitivity syndrome in the context of pediatric oncology and the supportive care measures that, if implemented rapidly, may diminish the reaction severity and allow successful completion of chemotherapy.

Topics: Amifostine; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Drug Hypersensitivity; Humans; Male; Mesna; Neuroectodermal Tumors, Primitive; Prognosis; Protective Agents; Sulfhydryl Compounds; Supratentorial Neoplasms

Nine patients (3 boys and 6 girls) with a median age of 9.5 years, with immediate type hypersensitivity reactions to chemotherapeutic agents were reviewed. The presenting symptoms were urticaria (4/9) and anaphylaxis (5/9). The causative agents were vincristine (2/9), L-asparaginase (2/9), mesna (1/9), cyclosporine (1/9), carboplatin (2/9) and cyclophosphamide (1/9). Three of the five patients with anaphylaxis were changed to alternative chemotherapeutic agents. In two cases alternative drugs were not available and the patients underwent safe and successful desensitization. Three of the 4 patients with urticaria were successfully exposed to graded challenges with cyclosporine, carboplatin and cyclophosphamide, respectively. In the other case with generalized urticaria, mesna was withdrawn due to a positive intradermal test. In patients with immediate type hypersensitivity reactions to chemotherapeutic drugs, if effective alternative chemotherapeutic agents are not available and/or the skin test is negative, a careful drug challenge and/or desensitization should be performed.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Carboplatin; Central Nervous System Neoplasms; Child; Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; Female; Glioma; Humans; Hypersensitivity, Immediate; Male; Mesna; Practice Guidelines as Topic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Skin Tests; Vincristine; Withholding Treatment

Topics: Adult; Cyclophosphamide; Cystitis; Drug Hypersensitivity; Female; Humans; Male; Mesna; Middle Aged

Topics: Cyclophosphamide; Drug Administration Schedule; Drug Hypersensitivity; Humans; Lupus Nephritis; Mesna

Topics: Adult; Drug Hypersensitivity; Female; Humans; Intradermal Tests; Mercaptoethanol; Mesna