mesna and Thrombocytopenia

The stage-by-stage prognosis for cervical cancer patients has not improved in the past decades. Our research work concerning adjuvant chemotherapy for the early stages induced a pilot study with untreated patients in advanced stages. Patients were treated with carboplatin 300 mg/m2 plus ifosfamide 5 g/m2 on day 1. In cases of remission or no change, the therapy was repeated after 4 weeks. A third course was given only after further remission. After chemotherapy, patients were treated with surgery or radiotherapy according to feasibility. A total of 34 patients were admitted to this study. Thirty-two patients with 88 chemotherapy courses were evaluable for response and toxicity. Nineteen patients achieved remission; three achieved complete remission. The most common toxic effects were myelosuppression with grade four leukopenia (28%) and thrombocytopenia (13%). Alopecia (60%) was the main nonhematologic toxicity. In conclusion, we suggest that this regimen is as effective as other platin-containing regimens for squamous cell carcinoma of the cervix uteri, but its hematologic toxicity precludes its recommendation in an adjuvant setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction; Thrombocytopenia; Uterine Cervical Neoplasms

Docetaxel, ifosfamide and cisplatin have proven activity in a broad range of solid tumours and interfere with different phases of the cell cycle. We performed a phase I study with the aim to determine the maximum tolerated dose (MTD) of docetaxel, ifosfamide and cisplatin in patients with solid tumours and to define the safety, dose-limiting toxicity (DLT) and the recommended dose and administration schedule of docetaxel, ifosfamide and cisplatin for further phase II testing. Docetaxel was given by 1-h infusion on day 1, followed by ifosfamide 1000 mg/m(2)/day as a continuous infusion for 5 days. Mesna was added at the same doses to the same infusion bag and was continued for 12 h after the end of ifosfamide. Cisplatin was administered as a 24-h infusion concomitantly with ifosfamide, but in separate infusion bags, either on day 5 (schedule A) or on day 1 (schedule B). Escalation steps were planned only for docetaxel (60, 75, 85 mg/m(2)) and cisplatin (50, 75, 100 mg/m(2)). No intrapatient dose escalation was permitted. Prophylactic ciprofloxacin was used after a protocol amendment was implemented. No prophylactic haematopoietic growth factors were used. Cycles of docetaxel, ifosfamide and cisplatin were given at 3-week intervals. Toxicity was scored according to National Cancer Institute Canada-Common Toxicity Criteria 2. The MTD was defined as the dose at which a DLT was observed in fewer than two of six patients during the first treatment cycle. In total, 85 patients received 309 cycles. Only three escalation steps could be explored and DLTs were observed at each dose level. In total, 32 patients and 49 cycles showed DLTs. Febrile neutropenia occurred in 20 patients (24%). Only two DLTs were nonhaematological (one cerebral infarction and one encephalopathy grade 4). Neutropenia grade 4 lasted for greater than 7 days and/or thrombocytopenia grade 4 was dose limiting in 10 patients. Febrile neutropenia occurred in five of 41 patients (12%) who received prophylactic ciprofloxacin and in 15 of 44 patients (34%) who did not. MTD was reached at level 3 (docetaxel, 75 mg/m(2) and cisplatin, 75 mg/m(2)). With a lower dose of docetaxel (60 mg/m(2)) both schedules A and B were feasible, although, overall, schedule A seemed to be better tolerated. On the basis of this phase I study, the recommended docetaxel, ifosfamide and cisplatin regimen is docetaxel (60 mg/m(2)) on day 1, ifosfamide (1000 mg/m(2)/day) on days 1-5 and cisplatin (75 mg/m(2)) given on day 5. It

Topics: Adult; Aged; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Brain Injuries; Canada; Cerebral Infarction; Cisplatin; Docetaxel; Drug Administration Schedule; Female; Humans; Ifosfamide; Male; Maximum Tolerated Dose; Mesna; Middle Aged; Neoplasms; Neutropenia; Taxoids; Thrombocytopenia

Most institutional teams utilize multimodality therapy in their efforts to cure patients with primary high-grade extremity soft tissue sarcomas, although the value of adjuvant systemic chemotherapy is still disputed by some oncologists. This single-institution Phase II study describes an effort to control metastasis by the use of two cycles of chemotherapy as the initial preoperative treatment.. Between March 1994 and October 1997, 20 women and 19 men with primary extremity or limb girdle high-grade soft tissue sarcomas were registered to a study of preoperative ifosfamide, mitomycin, doxorubicin, cisplatin (IMAP) plus granulocyte macrophage-colony-stimulating factor (GM-CSF) followed by preoperative irradiation and subsequent limb-sparing surgery. The two sequential monthly cycles of IMAP involved intravenous ifosfamide, 2500 mg/m(2), and mesna, 2500 mg/m(2), on Day 0, followed by identical doses of these agents plus intravenous mitomycin, 4 mg/m(2), doxorubicin, 40 mg/m(2), and cisplatin, 60 mg/m(2), on Day 1. Sargramostim (GM-CSF) 250 microg/m(2) was given subcutaneously every 12 hours for 4 days beginning 6 days before the chemotherapy, and then for 14 more days beginning the day after chemotherapy was completed. At the beginning of the third month, external beam irradiation was administered daily, 5 days each week for 5 consecutive weeks to total preoperative doses of 4500 centigrays (cGy). This was accompanied by reduced doses of MAP chemotherapy (mitomycin, 6 mg/m(2), doxorubicin, 30 mg/m(2), and cisplatin, 45 mg/m(2)) intravenously on Days 0, 21, and 42 of the radiation therapy segment. Approximately 1 month after preoperative irradiation ended, each patient had complete surgical excision with curative intent, using limb-sparing techniques when possible. Radiation to total doses of 5500-6500 cGy was accomplished by delivery of an additional 1000-2000 cGy to the tumor bed via intraoperative electron beam, brachytherapy, or external beam irradiation at the completion of surgery.. All except 5 patients had tumors at least 5 cm in diameter. Chemotherapy toxicity grade three or higher consisted primarily of vomiting (23%), leukopenia (54%), and thrombocytopenia (77%). Six patients have died of metastatic sarcoma, and one other died in a motorcycle accident. Kaplan-Meier curves indicate estimated 5-year survival of approximately 80% and freedom from metastasis at 2 years of approximately 85%.. IMAP plus GM-CSF is satisfactory as initial treatment for primary extremity soft tissue sarcomas in two monthly cycles preceding irradiation. The prescribed irradiation was generally tolerable and effective in permitting limb-sparing surgery. Although the outcome of patients treated on this regimen has been favorable, the metastasis problem has not been eliminated.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Ifosfamide; Infusions, Intravenous; Injections, Subcutaneous; Leukopenia; Male; Mesna; Middle Aged; Mitomycin; Neoadjuvant Therapy; Sarcoma; Soft Tissue Neoplasms; Thrombocytopenia; Treatment Outcome; Vomiting

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

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

This Phase I study was designed to determine the maximum tolerated dose of ifosfamide-mesna with a fixed dose of cisplatin without growth factor or hematopoietic precursor support.. Twenty-five patients with previously untreated advanced non-small cell lung cancer were treated at four dose levels. Initially, the cisplatin dose was 100 mg/m2 given on day 1. Seven patients were treated with ifosfamide 2.0 g/m2 days 1 to 3, and six patients received ifosfamide 2.5 g/m2 days 1 to 3. Mesna was given at 20% of the ifosfamide dose at 0, 4, and 6 hours after ifosfamide. Cycles were repeated every 4 weeks.. Dose-limiting toxicities (myelosuppression and renal toxicity) were seen at dose level 2 (ifosfamide 2.5 g/m2). Because 5 of the first 13 patients experienced Grade 3 renal toxicity, the study was amended to give cisplatin in divided doses. An additional six patients each were treated at dose level 3 (ifosfamide 2.0 g/m2 days 1-3) and dose level 4 (ifosfamide 2.5 g/m2 days 1-3) with cisplatin 33 mg/m2 days 1 to 3. Dose-limiting toxicity (myelosuppression) was reached at ifosfamide 2.5 g/m2. No further Grade 3 renal toxicity was seen. Grade 3 or worse toxicities were seen as follows: neutropenia 80%, thrombocytopenia 48%, nausea/vomiting 36%, anemia 32%, renal 20%, central nervous system 16%, and infection 16%. Two toxic deaths occurred, both with infection, renal failure, and neutropenia. Partial responses were seen in 8 of 25 eligible patients (32%).. The maximum tolerated dose in this group of patients was defined as ifosfamide 2.0 g/m2 days 1 to 3 when given with cisplatin 33 mg/m2 days 1 to 3. When combining high-dose cisplatin with ifosfamide, it is advisable to give cisplatin in divided doses.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Female; Fluid Therapy; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neutropenia; Thrombocytopenia; Vomiting

The stage-by-stage prognosis for cervical cancer patients has not improved in the past decades. Our research work concerning adjuvant chemotherapy for the early stages induced a pilot study with untreated patients in advanced stages. Patients were treated with carboplatin 300 mg/m2 plus ifosfamide 5 g/m2 on day 1. In cases of remission or no change, the therapy was repeated after 4 weeks. A third course was given only after further remission. After chemotherapy, patients were treated with surgery or radiotherapy according to feasibility. A total of 34 patients were admitted to this study. Thirty-two patients with 88 chemotherapy courses were evaluable for response and toxicity. Nineteen patients achieved remission; three achieved complete remission. The most common toxic effects were myelosuppression with grade four leukopenia (28%) and thrombocytopenia (13%). Alopecia (60%) was the main nonhematologic toxicity. In conclusion, we suggest that this regimen is as effective as other platin-containing regimens for squamous cell carcinoma of the cervix uteri, but its hematologic toxicity precludes its recommendation in an adjuvant setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction; Thrombocytopenia; Uterine Cervical 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

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m2 followed by a 24 h infusion of ifosfamide 5 g/m2 plus mesna 2.5 g/m2 repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28-42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Evaluation; Female; Humans; Ifosfamide; Leukopenia; Male; Mesna; Middle Aged; Sarcoma; Soft Tissue Neoplasms; Thrombocytopenia