mesna and Mesothelioma

Our aim was to determine the efficacy of ifosfamide, mesna, and interferon alpha combination therapy in malignant mesothelioma (MM) patients. Fourty-two patients (39 evaluable) with histologically proven MM were enrolled into this study from January 1999 to October 2002. The drug schedule consisted of a combination of ifosfamide, 3000 mg/m2 1-3 d intravenous infusion (iv), the uroprotective agent mesna, 3000 mg/m2 1-3 d iv every 3 wk, and interferon alpha2a, 4.5 MU subcutaneously (sc) 3 d/wk for 6 mo as first-line chemotherapy. Overall, 140 cycles were administered to the 39 patients (median, 3.5 cycles; range, 1 to 6 cycles). Among the 39 patients, 8 partial remissions (PR) (21%) were observed. Thirteen patients (33%) had stable disease for at least 8 wk and 18 (46%) had progressive disease. Overall survival (OAS) and progression free survival (PFS) for all patients were 10.0 +/- 2.9 mo (95%CI 4.3-15.7) and 5.0 +/- 1.9 mo (95%CI 1.38-8.62), respectively. One and two year survival rates were calculated as 39% and 5%, respectively. All of the PR patients had the epithelial type of MM. Their survival time was 21.0 +/- 5.7 mo (95% CI 9.9-32.1) and significantly longer than that of nonresponders (p=0.0061). The toxicity of the drug combination was mild and well tolerated. There were no treatment-related deaths. Grade 3-4 neutropenia and febrile neutropenia were seen in 10 patients (26%) and 3 patients (8%), respectively. Chemotherapy was stopped in three patients because of renal function deficiency. One of these patients who had peritoneal MM required hemodialysis. In conclusion, this combination therapy showed encouraging antitumor activity with modest toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Humans; Ifosfamide; Infusions, Intravenous; Interferon alpha-2; Interferon-alpha; Male; Mesna; Mesothelioma; Middle Aged; Neutropenia; Recombinant Proteins; Survival Analysis; Treatment Outcome

The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte-colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma.. Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 microg/kg/day was administered subcutaneously on days 6-15.. Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0-14%) and 1 was an unconfirmed response (3%; 95% CI, 5-14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3-7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6-9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure.. This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Disease-Free Survival; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Male; Mesna; Mesothelioma; Middle Aged; Pleural Neoplasms; Protective Agents; Recombinant Proteins; Treatment Outcome

This study investigated the feasibility and efficacy of doxorubicin dose-escalated chemotherapy in combination with ifosfamide in patients with malignant mesothelioma.. In this single institution phase II study, 24 chemotherapy-naive, eligible patients were entered. The chemotherapy regimen consisted of doxorubicin 75 mg/m2 in combination with ifosfamide 5 gr/m2 given as a continuous 24 hour infusion, every 21 days with either rhG-CSF (5 micrograms/kg) or rhGM-CSF (250 micrograms/m2) as haematopoietic support from d3 to d14. Cycles were repeated every 3 weeks.. We treated 24 patients, of whom 22 are evaluable for tumour response. One of the two inevaluable patients died from a cerebral haemorrhage during a period of grade III thrombocytopenia after the second course. In 7 patients a partial response was observed, resulting in a response rate of 32% (95% confidence interval 13%-51%). Median response duration was 6 months (range 1-13) and median survival was 7 months (range 1-18).. The high-dose regimen with growth factor support is feasible in this group of patients and leads to an interesting response rate. The limiting toxicity for further dose increments and more courses of treatment, was cumulative thrombocytopenia. There seems to be a subgroup of patients with malignant mesothelioma which is less susceptible to develop thrombocytopenia. However, the overall toxicity and the poor response duration limit the use of this schedule in the treatment of malignant mesothelioma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Feasibility Studies; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Ifosfamide; Leukopenia; Male; Mesna; Mesothelioma; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms; Remission Induction; Thrombocytopenia

Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy.. Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment.. Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters).. Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Ifosfamide; Male; Mesna; Mesothelioma; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms; Remission Induction; Survival Analysis; Testicular Neoplasms

Forty three patients with histologically confirmed malignant mesothelioma were entered onto an Eastern Cooperative Oncology Group phase II study of ifosfamide given with mesna. Eligibility criteria included adequate performance status, hemogram and renal functions. Ifosfamide was given at 1.5 g/m2 in 200 ml of normal saline over 30 minutes by intravenous infusion on days 1 to 5 of each 21 day cycle. Mesna was given at 300 mg/m2 on each day of ifosfamide at 0, 4 and 8 hours. Two patients were cancelled and one patient was ineligible. The most common toxicity was haematologic. More than 50% of the patients had at least one episode of severe or life threatening toxicity and 2 patients had lethal toxicity (1 renal and 1 pulmonary oedema attributed to treatment), and an additional 4 patients died while on study (2 of cardiac and 2 of cerebral vascular disease not considered directly related to treatment). Of the 40 eligible patients one was unevaluable for response, and one patient had a partial response lasting 6.3 months. Twenty four patients had a no change status with a median duration of 5 months. The median time to treatment failure for all eligible patients was 2.5 months. The median overall survival time (from registration) for all eligible patients was 6.9 months. In multi variable models, factors that predicted for a statistically significant poorer survival were age > or = 62, stage > or = 3, performance status poorer than 0 to 1 and prior surgery (i.e.: more than biopsy).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Drug Administration Schedule; Female; Humans; Ifosfamide; Infusions, Intravenous; Kidney Diseases; Male; Mesna; Mesothelioma; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms; Proportional Hazards Models; Survival Analysis

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Ifosfamide; Mesna; Mesothelioma

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Evaluation; Female; Humans; Ifosfamide; Male; Mesna; Mesothelioma; Middle Aged; Pleural Neoplasms

Topics: Adolescent; Adult; Aged; Drug Evaluation; Female; Humans; Ifosfamide; Kidney Diseases; Male; Mercaptoethanol; Mesna; Mesothelioma; Middle Aged; Pleural Neoplasms