mesna and Osteosarcoma

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cerebellar Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Hypersensitivity; Female; Humans; Medulloblastoma; Mesna; Osteosarcoma; Protective Agents; Spinal Neoplasms

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. The efficacy of chemotherapy varies according to the histological type of sarcoma. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy. On the other hand, the efficacy of chemotherapy is not statistically demonstrated in non-round cell sarcomas, e. g., malignant fibrous histiocytoma. Nowadays, several kinds of antitumor agents are usually used for adjuvant chemotherapy, and many authors have reported various kinds of regimens and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate, cyclophosphamide, dacarbazine, vincristine, and actinomycin-D. Recently, high-dose chemotherapy combined with autologous peripheral blood or bone marrow stem cell transplantation has been begun in patients who do not respond to standard chemotherapy, and a better prognosis is expected.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Dactinomycin; Doxorubicin; Drug Administration Schedule; Humans; Ifosfamide; Melphalan; Mesna; Methotrexate; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; Vincristine

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

Topics: Acidosis, Renal Tubular; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Doxorubicin; Humans; Ifosfamide; Leucovorin; Mesna; Methotrexate; Osteosarcoma; Postoperative Care; Preoperative Care; Radionuclide Imaging; Retrospective Studies; Salvage Therapy; Thallium Radioisotopes; Treatment Outcome

Patients with locally advanced or metastatic/recurrent soft tissue and Ewing's sarcoma (EWS) have few treatment options. The purpose of our phase II study was to assess the feasibility, safety and efficacy of tandem high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) in such patients.. Thirteen patients were enrolled onto this study. The first cycle of HDCT consisted of doxorubicin (150 mg/m(2)) and ifosfamide (14 g/m(2)) mixed with mesna (14 g/m(2)), while the second cycle consisted of melphalan (150 mg/m(2)) and cisplatin (200 mg/m(2)).. Eleven out of 13 patients were able to complete both cycles of HDCT. No treatment-related mortality occurred and grade 3 or 4 toxicity was clinically tolerable. The 5-year progression-free survival (PFS) and overall survival (OS) for all patients was 23% (confidence interval, CI: 0-46%) and 31% (CI: 14-70%), respectively. Out of the four patients still alive, two had EWS and measurable disease at the time of ASCT and achieved a complete remission, remaining progression free 126 and 155 months after ASCT.. Our study demonstrates the feasibility and safety of tandem HDCT in patients with high-risk or metastatic/recurrent sarcoma, with some patients achieving long-term PFS and OS.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Disease Progression; Doxorubicin; Feasibility Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Immunoenzyme Techniques; Male; Melphalan; Mesna; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma; Prognosis; Prospective Studies; Protective Agents; Remission Induction; Rhabdomyosarcoma; Safety; Sarcoma; Sarcoma, Ewing; Survival Rate; Transplantation, Autologous; Treatment Outcome; Young Adult

Ewing's sarcomas, osteosarcomas, and rhabdomyosarcomas are significantly more responsive to chemotherapy than other sarcomas. Adjuvant chemotherapy is used routinely based on data from randomized trials. Although a percentage of children with locally advanced or metastatic tumors remain curable, few data exist regarding the tumor's natural history or response and survival in adults.. This Phase II study evaluated doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma.. Between 1987-1991, 81 patients were entered; 69 patients were eligible. One patient died of neutropenic infection. Ten patients (14%) responded completely and 34 patients (49%) had a complete or partial response. Response rates were significantly higher for patients with Ewing's sarcoma and rhabdomyosarcoma than for those with osteosarcoma (77%, 64%, and 26%, respectively; P < 0.005). Although there were no significant differences in progression free survival by histology, survival for patients with Ewing's sarcoma was significantly longer than for patients with osteosarcoma (P = 0.004.) At the time of last follow-up, 7 patients (10%) were alive without progression: 3 with Ewing's sarcoma, 1 with osteosarcoma, and 3 with rhabdomyosarcoma.. MAID chemotherapy is an active regimen in adults with advanced or metastatic Ewing's sarcoma and rhabdomyosarcoma. Although there was no direct comparison with a doxorubicin and cisplatin-based regimen, the response rate and survival in patients with osteosarcoma suggest that doxorubicin and cisplatin-based chemotherapy would remain the accepted initial chemotherapy regimen. For patients with rhabdomyosarcoma and Ewing's sarcoma, 10-20% of patients remained disease free at 5 years.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Male; Mesna; Middle Aged; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Survival Rate; Treatment Outcome

The necrotic effect of chemotherapy on primary osteosarcoma has been shown to be predictive of the final outcome. Little attention has been paid to the local response of the host (LHR), which reflects the tumour-host relationship.. A four-step grading system was developed based on distinct histological patterns of the LHR around the lesion. These responses were correlated with the chemotherapy-induced necrosis or chemosensitivity and analysed in an attempt to ascertain their influence on the patient prognosis. The ability of conventional radiographs and computed tomography to measure LHR was studied.. The grading system was applied to macroslides of specimens obtained from 72 patients with stage II B primary osteosarcoma in various limbs after wide resection and complete courses of pre- and postoperative chemotherapy who were treated between 1985 and 1991 with a median follow-up of 5 years and 9 months. The histological specimens were blindly reviewed by two pathologists and two experienced musculoskeletal oncologists to assign a grade of response. The results were correlated with tumour necrosis, patient survival and response features on conventional radiographs and CT images.. Significant correlation was found between LHR and tumour necrosis or chemosensitivity (r=0.55) and between LHR and CT response (r=0.56). There was no correlation between LHR and the findings on conventional radiographs. A grade 4 LHR was predictive of long-term survival.. The LHR to preoperative chemotherapy has a prognostic influence on patient survival and can be predicted by CT.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Infant; Infant, Newborn; Male; Mesna; Methotrexate; Middle Aged; Necrosis; Neoadjuvant Therapy; Osteosarcoma; Predictive Value of Tests; Prognosis; Tomography, X-Ray Computed

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

To assess the role of preoperative radiotherapy in patients with nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery and to compare the response of neoadjuvant therapies, local control, and survival with the literature results.. Forty-six patients with osteosarcoma of the limbs who were treated within a limb salvage protocol including preoperative radiotherapy and chemotherapy between 1987 and 2002, were retrospectively analyzed. Median age was 17 years (range, 14-66 years). Treatment was started with neoadjuvant chemotherapy. Cisplatin, epidoxorubicin, ifosfamide, and methotrexate were used in different combinations. Preoperative radiotherapy was applied, usually between the second and third cycle of chemotherapy. Radiotherapy was given (35 Gy in 10 fractions) to 44 patients. Two patients were treated with 46 Gy at 2 Gy/day. Definitive surgery was administered after the third course of chemotherapy. Chemotherapy was complete 6 courses postsurgery.. Median follow-up time was 44 months (range, 2-154 months). Forty-four patients had limb-sparing surgery, whereas 2 had amputation. Tumor necrosis rate was >/=90% in 87% of the patients (Huvos Grade 3-4). Two patients had local failures, and 26 patients (56.5%) had distant metastases. The 5-year local control and overall survival rates were 97.5% and 48.4%, respectively. On univariate analysis, age

Topics: Adolescent; Adult; Aged; Amputation, Surgical; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Extremities; Humans; Ifosfamide; Limb Salvage; Male; Mesna; Methotrexate; Middle Aged; Osteosarcoma; Prognosis; Radiotherapy Dosage; Retrospective Studies; Survival Rate

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Female; Humans; Ifosfamide; Mesna; Methylene Blue; Neurotoxicity Syndromes; Oncology Nursing; Osteosarcoma

A patient underwent mandibular resection for high-grade osteosarcoma with immediate reconstruction with a microvascular fibula free bone graft and simultaneous placement of osseointegrated implants. Following initial healing, she underwent six cycles of chemotherapy and had further revision surgery prior to implant exposure and construction of a prosthesis. The chemotherapy appears to have had no deleterious effects on implant osseointegration or survival.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Transplantation; Cisplatin; Dacarbazine; Dental Care for Chronically Ill; Dental Implantation, Endosseous; Dental Implants; Doxorubicin; Female; Fibula; Humans; Ifosfamide; Mandibular Neoplasms; Mesna; Osseointegration; Osteosarcoma

We report the case of a patient with a rare miliary variant of osteosarcoma associated with symptomatic hypocalcemia and review the literature regarding the pathogenesis of multifocal osteosarcoma, treatment options, and the associated hypocalcemia.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Expectorants; Fatal Outcome; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Hypocalcemia; Ifosfamide; Lung Neoplasms; Mesna; Osteosarcoma

From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Neoplasms; Child; Drug Administration Schedule; Female; Histiocytoma, Benign Fibrous; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms

The objective of this study was to determine the tolerance and toxicities of high-dose cyclophosphamide (CPA) at 7 g/m2 given in four fractions over 8 h in children with advanced solid tumors.. Twenty children aged 1 1/2-19 years (median, 12 years) received 24 courses of high-dose CPA at 7 g/m2 for the treatment of advanced malignant solid tumor. CPA was given in four 1-h infusions of 1.75 g/m2 each, with 1 h of rest between each dose. MESNA was used as a uroprotective agent and was continued for 24 h after the final dose of CPA. With only one exception, all patients were discharged at the end of MESNA infusion and received granulocyte colony-stimulating factor, prophylactic ciprofloxacin, and co-trimoxazole.. Severe but transient myelosuppression was observed. The median time to neutrophil and platelet recovery was 17 and 19 days, respectively. Fever developed after 13 of the 24 courses, and hospitalization was required. Extramedullary toxicities were mild. No patient showed cardiomyopathy or hemorrhagic cystitis. Forty-six percent of the courses were managed entirely on an outpatient basis. Objective tumor response was seen in five patients.. CPA at 7 g/m2 is well tolerated by children with advanced malignancies and should be considered in earlier phases of antineoplastic therapy.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Cyclophosphamide; Drug Administration Schedule; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Infant; Male; Mesna; Neoplasms; Neuroblastoma; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Treatment Outcome

We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen. Microhematuria transiently occurred only in 2 courses (5%) of 1 patient (2%). These data indicated that mesna was highly effective for urotoxicity of oxazaphosphorines without any side effects, especially in pediatric patients.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Cystitis; Female; Hematuria; Humans; Ifosfamide; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Neuroblastoma; Osteosarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhabdomyosarcoma

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Drug Evaluation; Female; Hematologic Diseases; Humans; Ifosfamide; Infant; Lymphoma; Male; Mesna; Neoplasms; Nervous System Diseases; Neurilemmoma; Osteosarcoma; Urologic Diseases

The authors have had the opportunity to see two cases of CNS side effects of Ifosfamide-Mesna association in children. Data in the medical literature about this subject remains poor. Only a few observations are available. In the referred cases, CNS side effects (lethargy, apathy and mutism) appeared a few hours after the second day of treatment and were spontaneously reversible in a few days. After reviewing possible mechanisms of this toxicity the authors pointed out the necessity to keep this type of side effects of Ifosfamide-Mesna association in mind, and to avoid it in susceptible patients.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Central Nervous System Diseases; Child; Female; Humans; Ifosfamide; Mesna; Osteosarcoma

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

Topics: Female; Humans; Ifosfamide; Infusions, Intravenous; Male; Mercaptoethanol; Mesna; Middle Aged; Osteosarcoma; Soft Tissue Neoplasms

Ifosfamid is an alkylating cytostatic agent which appears to differ in its clinical spectrum from the chemically similar cyclophosphamid. So far, however, its pronounced urotoxicity has limited dosage. In spite of prophylactic measures such as forced diuresis and alkalinization of the urine, the treatment has frequently has to be broken off because of macrohematuria and hemorrhagic cystitis. By repeated intravenous administration of sodium-mercapto-ethan-sulfonate (NNI: Mesnum) the urotoxic side effects of ifosfamid can largely be prevented. During 26 cycles of treatment in 18 patients, asymptomatic microhematuria was observed 6 times and macrohematuria only once in a patient with vesico-vaginal fistula. In another case where therapy had had to be discontinued because of hemorrhagic cystitis in spite of conventional prophylaxis, the treatment could be continued without change in the urine sediment under prophylaxis with Mesnum. Mesnum does not affect the antitumoral activity of ifosfamid.

Topics: Adult; Cyclophosphamide; Cystitis; Hematuria; Humans; Ifosfamide; Male; Mercaptoethanol; Mesna; Osteosarcoma