mesna and Anemia

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

We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787.. Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and /=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B].. This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Darbepoetin alfa; Docetaxel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Feasibility Studies; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Polyethylene Glycols; Prognosis; Recombinant Proteins; Survival Rate; Taxoids

Adriamycin (ADM) and ifosfamide (IFO) are the two most active agents in the treatment of soft tissue sarcomas (STS) with a clear dose-response relationship. We evaluated the feasibility and toxicity of a high-dose IFO-plus-ADM combination.. Fourteen patients with advanced disease and nine patients in adjuvant setting received IFO 12.5 g/m2 in 120-hour continuous infusion with Mesna uroprotection and ADM 20 mg/m2 on days 1-3 and G-CSF every three weeks.. Twenty-three patients received 89 chemotherapy cycles (70 cycles at full dose). Seventeen patients received the planned treatment, and nine patients required dose reductions. We observed grade 3-4 neutropenia in 52 cycles (59%)/20 patients; grade 3-4 thrombocytopenia in 16 cycles (18%)/nine patients; grade 3-4 anaemia in 24 cycles (27%)/11 patients. Eight patients experienced febrile neutropenia and six patients required blood transfusions.. While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Infusions, Intravenous; Male; Mesna; Middle Aged; Neutropenia; Sarcoma; Soft Tissue Neoplasms; Thrombocytopenia

Recombinant human erythropoietin (r-Hu-EPO) is known to be effective in untreated cancer patients. Here we assess the possibility that r-Hu-EPO may also prevent or reduce anemia in patients who receive cytotoxic chemotherapy.. Thirty-six patients with small-cell lung carcinoma (SCLC) were enrolled onto a three-arm, randomized trial to investigate the effect of r-Hu-EPO on hemoglobin (Hb) levels and RBC and platelet (Plt) transfusions during chemotherapy. Bone marrow progenitors were studied before and after treatment. Two groups of patients received r-Hu-EPO at a dose of either 150 IU/kg (group 150) or 300 IU/kg (group 300) three times per week for the duration of chemotherapy. A control group did not receive r-Hu-EPO (group O). A maximum of six cycles of a chemotherapy regimen that consisted of vincristine, ifosfamide, carboplatin, and etoposide (VICE) were given to all patients. Hematologic parameters were measured weekly, and RBC or Plt transfusions were given for Hb levels less than 9 g/dL and Plt counts less than 20 x 10(9)/L.. Hb levels decreased in all patients, but onset of anemia was delayed in groups that received r-Hu-EPO (P = .002). A total of 116 U RBC were transfused in group 0, 54 in group 150, and 52 in group 300 (P = .017). In addition, there was a nonsignificant trend toward higher Plt counts and fewer Plt transfusions in patients who received r-Hu-EPO.. r-Hu-EPO at a dose of either 150 or 300 IU/kg three times weekly delays the onset of anemia and reduces RBC transfusion requirements in patients who undergo intensive chemotherapy for SCLC. A possible effect of r-Hu-EPO on platelet numbers deserves further study.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Colony-Forming Units Assay; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Etoposide; Female; Granulocytes; Hemoglobin A; Humans; Ifosfamide; Iron; Leukocyte Count; Lung Neoplasms; Macrophages; Male; Mesna; Middle Aged; Platelet Count; Platelet Transfusion; Recombinant Proteins; Vincristine

A retrospective study to evaluate six cycles of cisplatin 40 mg/m2 on day 1 and ifosfamide 1,200 mg/m2 daily on days 1 to 4 with Mesna every four weeks as first line treatment for 29 patients with a diagnosis of uterine carcinosarcoma.. A total of 23 of 29 patients received high dose rate intracavitary vaginal cuff brachytherapy (VCBT) with two fractions of seven Gy each. Median age was 65 years (range 40-82); 13 (44.8%) had Stage I disease, three (10.3%) had Stage II, eight (27.6%) had Stage III, and five (17.2%) patients had Stage IV disease.. Most common toxicities were anemia grade 1 (35%)/grade 2 (45%), and neutropenia grade 3 (17%)/grade 4 (6.9%). Eleven dose modifications, four treatment discontinuations, and one patient withdrawal occurred. At a median follow up of 45 months (range 9 to 144), Progression free survival (PFS) was 20% and overall survival (OS) was 40% for Stage IV, PFS 75% and OS 62.5% for Stage III, compared to a PFS 75% and OS 72.2% for Stages I-II. Median OS for the entire group was 12.43 years (95% CI 3.69 to inf); for Stage I-III 12.4 years (6.1 to inf), and for Stage IV 15.6 months (95% CI 9.4 to inf).. Cisplatin and ifosfamide chemotherapy with VCBT was well tolerated and has promising activity in uterine carcinosarcoma.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinosarcoma; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Protective Agents; Retrospective Studies; Treatment Outcome; Uterine Neoplasms

Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.. AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years.. In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.. Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.

Topics: Adolescent; Age Factors; Anemia; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Doxorubicin; Epirubicin; Female; Humans; Ifosfamide; Incidence; Male; Mesna; Neutropenia; Rhabdomyosarcoma; Sex Characteristics; Survival Rate; Thrombocytopenia; Vincristine; Young Adult

Ifosfamide is an alkylating agent which has poorly understood toxic side effects such as encephalopathy. We hypothesized that ifosfamide and concomitantly applied mesna could have an influence on the flow properties of blood, and thus carried out an in vitro study. Whole blood was incubated in vitro with increasing concentrations of ifosfamide (0-50 mg/ml), mesna (0-20 mg/ml) and combinations thereof. Chloroacetaldehyde, a major metabolite of ifosfamide, was also studied (0-5 mmol/l). Ifosfamide led to a dose-dependent stomatocytic shape transformation and mesna to an echinocytic shape transformation of erythrocytes. These shape changes were reversible upon removal of the causing agent. Both shape changes increased whole blood viscosity. Erythrocyte aggregation was decreased by both drugs at high concentration. Erythrocyte deformability, as measured with the transit time through 5-microm pores, was decreased by mesna and remained unaffected by ifosfamide. These effects were seen at concentrations which may be reached in vivo at the infusion site of the drugs into a vein and in the urinary tract. We conclude that ifosfamide and mesna interact with the lipid bilayer of the cell membrane, which may contribute to the toxicity of the compounds.

Topics: Adult; Anemia; Antineoplastic Agents, Alkylating; Cell Aggregation; Erythrocyte Deformability; Erythrocytes; Humans; Ifosfamide; In Vitro Techniques; Mesna; Microscopy, Electron, Scanning; Protective Agents; Rheology

Ifosfamide was studied in advanced pancreatic tumor at the National Cancer Institute, Cairo. Over five years, 25 patients received a daily dose of 1.8 g ifosfamide for five days, courses reported every 21 days. Complete remission was achieved in 1 patient and partial remission in 14 patients, an overall result of 60%, average duration of response being 12+ months. Mesna was used for uroprotection.

Topics: Adult; Alopecia; Anemia; Drug Evaluation; Female; Humans; Ifosfamide; Leukopenia; Male; Mesna; Middle Aged; Pancreatic Neoplasms