mesna and Fever

In aggressive non-Hodgkin lymphoma (NHL), CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) regimen has been standard for decades, and rituximab has increased response rates and survival in CD20 positive patients, recently. The aim of this prospective trial was to evaluate the long-term efficacy and toxicity of MINE as a consolidation treatment in aggressive NHL patients who had achieved CR or unproven CR after six cycles of CHOP in the first line setting. The primary end-point was disease-free-survival (DFS). Thirty-eight patients were enrolled between February 1992 and May 2000. All of the patients received two cycles of MINE (mesna 1.3 g/m(2), ifosfamide 1.3 g/m(2), etoposide 65 mg/m(2) on days 1-3, and mitoxantrone 12 mg/m(2) on day 1, every 3 weeks) following response to CHOP. Initial bulky disease sites were also applied radiotherapy. Male/female ratio was 1.53(23/15). Median age was 49(30-73). Most of the patients had advanced stage (84.2% for stage >3) and high IPI score (79% for IPI score >2). Sixty percent had diffuse large cell histology. Median follow-up time was 118 months (9-195). Actual mean dose intensity was 88%. There were seven febrile neutropenia episodes. Two patients had grade two neuropathy, one had grade three mucositis and another one had non-neutropenic pneumonia. There was no early toxic death. No serious late toxicity was observed during long-term follow-up. Five- and 10-year DFS rates were both 65.3%. DFS rate in the patients with more than two poor prognostic factors according to IPI score is remarkably high (88%). Five- and 10-year OS was 62.5 and 59%, respectively. MINE regimen seems to be effective as a consolidation regimen, especially, in intermediate/high risk patients and has low early and late toxicities, and it warrants to be evaluated in phase III randomised trials with rituximab in CD20 positive aggressive NHL patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Fever; Follow-Up Studies; Humans; Ifosfamide; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Peripheral Nervous System Diseases; Prednisolone; Prospective Studies; Radiotherapy, Adjuvant; Remission Induction; Treatment Outcome; Vincristine

A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy. The patient subsequently developed fever and neutropenia and was administered 20.8 g of acetaminophen during 10 days. During this time, anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental status developed. After usual causes of high anion gap acidosis were ruled out, a screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold greater than normal values. Predisposing factors in this case included renal dysfunction and sepsis. Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N -acetylcysteine could be beneficial.

Topics: Acetaminophen; Acid-Base Equilibrium; Acidosis; Adult; Analgesics, Non-Narcotic; Antineoplastic Combined Chemotherapy Protocols; Bicarbonates; Candidiasis; Chlorides; Cytarabine; Etoposide; Fatal Outcome; Fever; Humans; Ifosfamide; Kidney Tubular Necrosis, Acute; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Male; Mesna; Neutropenia; Polycystic Kidney, Autosomal Dominant; Pyrrolidonecarboxylic Acid; Salvage Therapy; Systemic Inflammatory Response Syndrome

Our objective was to assess the efficacy of a standard dose ifosfamide and doxorubicin containing regimen in the treatment of advanced soft tissue sarcomas. Forty consecutive patients with a median age of 35.5 years were treated. Ifosfamide was administered at a dose of 2.5 g/m(2)/day as 72-hour continuous infusion with mesna at the same dosage and schedule. Doxorubicin was given at the dose of 60 mg/m(2)/day as 2-hour infusion on day 1. Six patients had a complete response (15%), and 9 (22.5%) had a partial response, fourteen patients (35%) stable disease, and 11 (27.5%) did not respond to chemotherapy. The median duration of response was 13 and 5 months for the complete and partial responders, respectively. The median survival was 37 months. Febrile neutropenia was encountered in 9 cases (22.5%). The present ifosfamide and doxorubicin combination is a moderately effective and well-tolerable regimen in the treatment of advanced soft tissue sarcomas.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Fever; Follow-Up Studies; Humans; Ifosfamide; Infusions, Intravenous; Logistic Models; Male; Mesna; Middle Aged; Neutropenia; Protective Agents; Remission Induction; Sarcoma; Survival Rate

The purpose of this study was to develop a canine experimental model for neoadjuvant chemotherapy of primary bone tumors with ifosfamide, which is safe and clinically relevant for use in human beings with bone tumors. Our study was divided into two steps, each with four dogs. In the first step ifosfamide was administered for 4 consecutive days in three cycles with 3-week intervals between each cycle. For this first step a daily dosage of 300 mg/m2 of body surface resulted in only moderate leukopenia, whereas a daily dosage of 450 mg/m2 caused severe leukopenia. Therefore, to determine the maximal dose tolerable and to verify the results from step 1, we administered the higher daily dosage of 450 mg/m2 in step 2 for four successive cycles with 3-week intervals. In each step one dog died acutely after the first cycle of chemotherapy. In addition during step 2 one dog died of overwhelming sepsis after the second cycle of ifosfamide. The remaining five dogs survived without other appreciable laboratory abnormalities. Neither hematuria nor proteinuria was observed throughout the course of study, and relevant findings were not observed at autopsy. We determined that 450 mg/m2 was the maximal tolerated dosage of ifosfamide for our regimen, with the dose-limiting factor being myelosuppression, specifically leukopenia. Using this canine model, we can estimate the effect of ifosfamide on bone graft incorporations and the fixation of biologic prostheses that is clinically the most important aspect of limb salvage surgery.

Topics: Animals; Antineoplastic Agents, Alkylating; Blood Platelets; Bone Neoplasms; Dogs; Drug Administration Schedule; Erythrocyte Count; Fever; Ifosfamide; Leukopenia; Male; Mesna; Survival Rate