mesna and Nausea

Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of ifosfamide should be repeated doses over several days. With the development of 5-day infusion devices, we developed and evaluated a 5-day infusion regimen of ifosfamide in sarcoma patients in the outpatient setting.. Sarcoma patients requiring chemotherapy after at least one doxorubicin-based line were enrolled in this study. Ifosfamide+mesna was administered as 1:1 concentration for a total of 6 g/m2 of each over 5 days (i.e. 1.2 g/m2 per day as continuous infusion) every 3 weeks. Patients were treated until progression or limiting toxicity, and salvage surgery was attempted when possible. An economic study was run comparing ifosfamide plus mesna as a 5-day infusion regimen and conventional Ifosfamide regimen.. Thirteen sarcoma patients were evaluable. The median number of cycles per patient was 6 (range, 1-8), for a total of 69 cycles. No acute encephalopathy or aggravation of renal function was noted. Acute grade 3 and 4 haematological toxicities were observed in 11.6 and 1.4% of patients, respectively without febrile neutropenia. Median time to progression survival and overall survival were 8.7 and 21.5 months, respectively. Total cost per cycle for a 2-m2 patient body surface area was ambulatory infusion=1,891 euros and conventional ifosfamide=6,256 euros.. The combination of ifosfamide and mesna as a continuous infusion over 5 days is feasible and well tolerated in the outpatient setting using infusion device. Its very favourable cost-effectiveness invites to further develop this approach.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Female; Humans; Ifosfamide; Infusion Pumps; Male; Mesna; Middle Aged; Nausea; Outpatients; Pilot Projects; Sarcoma; Survival Analysis; Time Factors; Treatment Outcome; Vomiting

Chemotherapy combined with other therapeutic modalities is the main option for advanced and metastatic soft tissue sarcoma(STS). So far there is no standard regimen for STS yet. Adrimycin, ifosfamide, and dacarbazine are the most effective agents at present. The purpose of this clinical trial was to evaluate the efficacy and toxicity of MAID regimen (mesna/ifosfamide + Adriamycin + dacarbazine) in the treatment of advanced soft tissue sarcoma.. Twenty-two patients with advanced STS were treated by MAID(Adriamycin 60 mg/m2, ifosfamide 6,000 mg/m2, and dacarbazine 1,000 mg/m2). These drugs were administered as continuous intravenous infusion for 72 hours while mesna was infused continuously for 96 hours.. Partial response rate was 36.4% without complete remission. The duration of response ranged from 2-10 months with median of 4.6 months. Main toxicities were myelosuppression, gastrointestinal toxicity and alopecia. Percentage of leucopenia, nausea/vomiting, and alopecia in WHO grade III and IV were 63.6%, 27.3%, and 50%, respectively.. The response rate of MAID for advanced STS was not satisfactory with evident myelosuppression. Further study on new anti-cancer agents and regimen are needed.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Infusions, Intravenous; Leukopenia; Male; Mesna; Middle Aged; Nausea; Sarcoma; Soft Tissue Neoplasms; Treatment Outcome; Vomiting

We have carried out a phase II study in advanced or metastatic transitional cell carcinoma of the bladder. Eligible patients had unresectable bladder cancer, previously treated with one line of systemic chemotherapy. Treatment consisted of ifosfamide 1000 mg/sm in a 2-hour infusion for 5 consecutive days from d.1 to d.5. Mesna was administered intravenously at a 20% of the ifosfamide dosage before ifosfamide and orally at 40% after 4 and 8 hours from the ifosfamide infusion. Twenty patients entered the study and received a total of 62 cycles: the treatment resulted feasible on an outpatient basis, with mild toxicity. Only one partial response was observed. With this dose and schedule, ifosfamide appeared less effective than in a previous report at higher doses. Toxicity was acceptable.

Topics: Administration, Oral; Aged; Alopecia; Ambulatory Care; Antineoplastic Agents, Alkylating; Bone Marrow; Carcinoma, Transitional Cell; Cause of Death; Disease Progression; Drug Administration Schedule; Expectorants; Feasibility Studies; Female; Humans; Ifosfamide; Infusions, Intravenous; Lymphatic Metastasis; Male; Mesna; Middle Aged; Nausea; Neoplasm Staging; Remission Induction; Survival Rate; Urinary Bladder Neoplasms; Vomiting

This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy.. Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner.. Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles.. Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Double-Blind Method; Doxorubicin; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematuria; Hemoglobins; Humans; Ifosfamide; Injections, Subcutaneous; Length of Stay; Lenograstim; Leukocyte Count; Male; Mesna; Middle Aged; Nausea; Neutropenia; Platelet Count; Recombinant Proteins; Regression Analysis; Sarcoma; Soft Tissue Neoplasms; Stomatitis

Mitomycin, ifosfamide, and cisplatin have demonstrated the best single-agent activity thus far in patients with non-small cell lung cancer (NSCLC), the most common malignant disease in the western world. For this reason, we initiated a phase II study, giving these three agents in combination (designated MIC) to 74 patients with inoperable NSCLC. Sixty-six patients were evaluable for response, of whom 30 (45%) demonstrated a partial response and 7 (11%) a complete response. These results, along with those obtained in two other phase II trials of MIC in NSCLC, promoted us to begin a large-scale, multicenter, phase III study of MIC in patients with inoperable limited-stage NSCLC. In this ongoing study, patients have been randomized to receive treatment with MIC and radiotherapy or radiotherapy alone. We hope to resolve the issue of whether a survival advantage is conferred on NSCLC patients treated with radiotherapy in combination with this promising chemotherapeutic regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Dexamethasone; Drug Administration Schedule; Furosemide; Humans; Ifosfamide; Lung Neoplasms; Mesna; Metoclopramide; Mitomycin; Mitomycins; Nausea; Neoplasm Staging; Vomiting

Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to $890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained.

Topics: Adult; Aged; Drug Administration Schedule; Drug Evaluation; Female; Hematuria; Humans; Ifosfamide; Infusions, Intravenous; Leukopenia; Male; Mesna; Middle Aged; Nausea

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

Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m2 ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m2 mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Mitomycins; Nausea; Remission Induction; Vomiting

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cisplatin; Etoposide; Evaluation Studies as Topic; Humans; Ifosfamide; Kidney Diseases; Leukopenia; Male; Mesna; Mesonephroma; Nausea; Sepsis; Teratoma; Testicular Neoplasms

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

Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported.

Topics: Adolescent; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Doxorubicin; Female; Humans; Ifosfamide; Kidney Diseases; Leukopenia; Male; Mesna; Middle Aged; Nausea; Sarcoma; Soft Tissue Neoplasms; Vomiting

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cisplatin; Humans; Ifosfamide; Mesna; Nausea; Osteosarcoma