mesna and Leiomyosarcoma

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Multicenter Studies as Topic; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Remission Induction; Uterine Cervical Neoplasms; Uterine Neoplasms

Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.. A-44-years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six-day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice-weekly dialysis order.. Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N-acetylcysteine may be effective in the prevention of this nephrotoxicity.

Topics: Acetylcysteine; Acute Kidney Injury; Creatinine; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Urea

Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial.. A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging.. In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.

Topics: Antineoplastic Combined Chemotherapy Protocols; Axilla; Doxorubicin; Female; Humans; Ifosfamide; Leiomyosarcoma; Lymph Node Excision; Mastectomy; Mesna; Middle Aged; Neoadjuvant Therapy; Protective Agents; Rare Diseases; Unilateral Breast Neoplasms

The patient was a 39-year-old man hospitalized due to the presence of a cardiac mass and heart failure. Emergency tumor resection and mitral valve replacement were performed. The pathological findings of the tumor led to a diagnosis of cardiac leiomyosarcoma. After the operation, multiple metastases were found. The patient underwent three courses of chemotherapies: adriamycin, ifosfamide, dacarbazine, and mesna (MAID therapy), gemcitabine plus docetaxel, and sunitinib. During MAID therapy, the patient underwent resection of gastrointestinal metastases twice due to gastrointestinal hemorrhaging. Although he died 27 months after the initial treatment, use of multimodal therapy was effective in achieving a longer survival for the patient.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dacarbazine; Deoxycytidine; Docetaxel; Doxorubicin; Fatal Outcome; Gemcitabine; Heart Neoplasms; Humans; Ifosfamide; Indoles; Leiomyosarcoma; Life Support Care; Male; Mesna; Pyrroles; Sunitinib; Taxoids

The prognosis of uterine leiomyosarcoma (LMS) is notoriously poor and a standard chemotherapy for patients with uterine LMS has not yet been established. Here, we describe two patients with recurrent LMS of the uterus who were treated with mesna, doxorubicin, ifosfamide and dacarbazine chemotherapy; one achieved complete and the other partial remission.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Uterine Neoplasms

The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas.. Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion.. The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction.. Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Adjuvant; Female; Humans; Ifosfamide; Infusions, Intravenous; Leiomyosarcoma; Mesna; Middle Aged; Mixed Tumor, Mullerian; Neoplasm Staging; Protective Agents; Rhabdomyosarcoma; Sarcoma; Survival Analysis; Uterine Neoplasms

Primary cardiac leiomyosarcoma is a rare malignant tumor in childhood. Patients with unresectable or partially resected cardiac leiomyosarcoma typically have a poor prognosis. The role of chemotherapy in the treatment of these patients has not been well defined.. A 6-week-old infant with an incompletely resected cardiac leiomyosarcoma was treated postoperatively with ifosfamide and etoposide.. The patient is disease-free and without apparent late effects 5 years following the completion of therapy.. The combination of ifosfamide and etoposide warrants further evaluation in patients with leiomyosarcoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Etoposide; Follow-Up Studies; Heart Neoplasms; Humans; Ifosfamide; Infant; Leiomyosarcoma; Mesna; Microscopy, Electron; Time Factors

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Base Sequence; DNA Mutational Analysis; DNA Primers; Doxorubicin; Exons; Follow-Up Studies; Gene Deletion; Genes, DCC; Genes, p53; Humans; Ifosfamide; Immunohistochemistry; Leiomyosarcoma; Male; Mesna; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Survival Analysis; Tumor Suppressor Protein p53

The purpose of this study was to evaluate the activity of ifosfamide (isophosphamide) in patients with advanced or recurrent leiomyosarcoma not previously exposed to chemotherapy.. This is a phase II groupwide study of the Gynecologic Oncology Group. Thirty-five patients were treated with ifosfamide 1.5 gm/m2 daily intravenously for 5 days with mesna (mercaptoethane sodium sulfonate). Fifty-six patients had received prior abdominal hysterectomy and 15 prior radiotherapy. The dose was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy.. Gynecologic Oncology Group grade III or IV granulocytopenia occurred in 4 (11%) patients, and none had grade IV thrombocytopenia. One (2.8%) patient had grade IV neurotoxicity. Partial responses were observed in 6 of 35 (17.2%) patients. The 95% confidence interval for response was 6.6% to 33.7%.. These results indicate that ifosfamide has modest activity in patients with advanced or recurrent leiomyosarcomas of the uterus.

Topics: Adult; Aged; Agranulocytosis; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Remission Induction; Uterine Neoplasms

A case report of a woman with perineal leiomyosarcoma who was cured by combination chemotherapy is presented, and the literature on chemotherapy of soft tissue is reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Perineum; Soft Tissue Neoplasms; Vincristine

Topics: Adult; Cyclophosphamide; Fanconi Syndrome; Female; Humans; Ifosfamide; Intestinal Neoplasms; Leiomyosarcoma; Mercaptoethanol; Mesna