mesna and Leukopenia

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

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

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

The combination of ifosfamide and mesna was evaluated in a phase II trial in the treatment of metastatic prostate cancer. Two separate groups of patients were to be evaluated: patients with no prior hormonal therapy and hormonally refractory patients. Patients were treated with ifosfamide 1.5 g/M2, and mesna at 30% of the ifosfamide dose was administered immediately before and 4 and 8 h after ifosfamide treatment. Both drugs were given i.v. daily for 5 days every 21 days. Response was assessed every 6 weeks. Of 29 eligible and evaluable patients with hormonally refractory disease, there were two partial responders for a response rate of 7% (95% confidence interval, of 0.1-23%). Of nine eligible patients with no prior hormone treatment, there was one partial response, for a response rate of 11% (95% confidence interval, 0.3-48%). Unfortunately, the target accrual goal for this arm of the study was never achieved. The most common toxicities were myelosuppression and neurologic toxicity. These drugs do not warrant further evaluation in the disease.

Topics: Adenocarcinoma; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Follow-Up Studies; Humans; Ifosfamide; Injections, Intravenous; Leukopenia; Male; Mesna; Neurologic Examination; Prostatic Neoplasms; Remission Induction; Survival Rate

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Brain; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Administration Schedule; Expectorants; Female; Humans; Ifosfamide; Leukopenia; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Staging; Peripheral Nerves; Phlebitis; Remission Induction; Survival Rate; Treatment Failure; Vinblastine; Vinorelbine

Since dose intensity of doxorubicin is correlated with the clinical response of patients with soft tissue sarcomas and since doxorubicin dose intensity may be compromised in combination chemotherapy, we evaluated the use of recombinant granulocytemacrophage colony-stimulating factor (rGM-CSF) to ameliorate myelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m2/day x 4 days, Adriamycin (doxorubicin) 15 mg/m2/day x 4 days, ifosfamide 2.0 g/m2/day x 3 days, dacarbazine 250 mg/m2/day x 4 days; to be repeated every 21 days]. Thirteen patients were treated. The doxorubicin dose for the first 6 patients was at the standard dose of 15 mg/m2/day x 4 days (level 1), while the doxorubicin dose for the next 7 patients was escalated by 25% to 18.75 mg/m2/day x 4 days (level 2). rGM-CSF was given at 5 micrograms/kg/day, days 5-14. All patients experienced moderate to severe myelosuppression, with all patients at dose level 2 requiring doxorubicin dose reduction to dose level 1 or lower by their third course of treatment. rGM-CSF failed to allow sustained escalation of the doxorubicin dose in the MAID regimen.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Dacarbazine; Doxorubicin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Ifosfamide; Leukopenia; Mesna; Recombinant Proteins; Sarcoma; Treatment Failure

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

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

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

One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin.

Topics: Adolescent; Adult; Aged; Cyclophosphamide; Drug Evaluation; Female; Humans; Ifosfamide; Infections; Leukopenia; Male; Mesna; Middle Aged; Random Allocation; Sarcoma; Soft Tissue Neoplasms

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

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

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

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

Fourteen evaluable patients with gynecologic adenocarcinoma (7 ovarian, 4 endometrial, 2 peritoneal and one breast cancer) were treated with ifosfamide (1 g/m2 X 5 days), adriamycin (50 mg/m2) and cisplatin (50 mg/m2) combined chemotherapy (IAP). All the patients had measurable disease, and three were refractory cases who had received prior chemotherapy including two CAP (cyclophosphamide, adriamycin and cisplatin). To avoid hemorrhagic cystitis induced by ifosfamide, uroprotective mesna (400 mg/body X 3) was used following ifosfamide infusion. The 5-day schedule of IAP treatment brought a 100% response rate in these patients. Complete responses were observed in 3 patients and lasted 6, 10 and 12 months. Partial responses were achieved in 11 patients including two with CAP refractory ovarian cancer, although the remission in previously treated patients was of short duration. Hematologic side effects of the IAP regimen were severe, showing grade 4 leucopenia in 85.7% of the patients, and it required maximal anti-infection treatments. Mesna resulted in microhematuria in only one patient. Despite high age of the patients (mean age: 60.1 years) in this study, CNS (central nervous system) toxicities associated with ifosfamide and mesna treatment were minimal. The results suggested that the IAP combination therapy was effective and acceptable in the control of gynecological adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Evaluation; Female; Genital Neoplasms, Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction

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

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

One of the serious toxicities of cyclophosphamide chemotherapy is urotoxicity. In addition to causing leukopenia, high-dose cyclophosphamide caused both depression of hepatic microsomal enzyme activities and extensive urinary bladder damage, suggesting that a common biochemical mechanism may be responsible for both of these effects. Administration of 180 or 200 mg cyclophosphamide per kg to Wistar rats caused 41 to 67% decrease in aryl hydrocarbon hydroxylase activity, a 21 to 54% decrease in aminopyrine demethylase activity, and a 34 to 40% decrease in cytochrome P-450 content. This dose of cyclophosphamide also caused hematuria as well as necrosis and edema in the urinary bladder. Administration of N-acetylcysteine or sodium-2-mercaptoethane sulfonate (mesnum) with cyclophosphamide, while not protecting against leukopenia, protected against the enzymatic inactivation and urotoxicity. The biochemical basis of these observations is discussed. The results suggest that a common metabolite of cyclophosphamide, most probably acrolein, is responsible for both of these undesirable effects of cyclophosphamide therapy. Use of combinations including cyclophosphamide and an appropriate thiol may increase the therapeutic index of this drug.

Topics: Acetylcysteine; Aminopyrine N-Demethylase; Animals; Aryl Hydrocarbon Hydroxylases; Cyclophosphamide; Cytochrome P-450 Enzyme System; Leukopenia; Liver; Male; Mercaptoethanol; Mesna; Mixed Function Oxygenases; NADPH-Ferrihemoprotein Reductase; Oxidoreductases; Rats; Rats, Inbred Strains; Urinary Bladder

Thirty-two patients with advanced cancer were treated in a phase I-II trial with ifosfamide plus mesnum. At doses up to 300 mg ifosfamide/kg the administration of mesnum prevented most of the expected kidney and bladder toxicity. With this high dose range hemopoietic dose-limiting. Only one of twelve evaluable patients with breast cancer showed definite therapeutic benefit. Complete remission or partial remission was seen in three patients with non-Hodgkin lymphoma and one patient with Hodgkin's disease.

Topics: Adult; Aged; Cyclophosphamide; Female; Humans; Ifosfamide; Kidney Diseases; Leukopenia; Male; Mercaptoethanol; Mesna; Middle Aged; Neoplasms; Urinary Bladder Diseases