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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcomas are a relatively rare and heterogeneous group of malignant tumors of principally mesenchymal origin. The histologic grade and size (and possibly compartmental localization) are the main factors predicting local and distant biologic aggressiveness. Tumor localization and surgical margins are significant prognostic factors that relate to the adequacy of local-regional therapy. A general consensus management usually consists of an incisional biopsy for diagnosis and grade, staging of the primary tumor and lungs, and function-preserving surgery with margins free of tumor either followed by or preceded by tumor bed high-dose radiotherapy. Each of these concepts remains under active investigation. The role of adjuvant therapy is not yet established despite tantalizing biologic effects documented in their trials. Ifosfamide in addition to doxorubicin does appear to have major activity; however, further laboratory investigation of resistance and metastases mechanisms and new drug evaluations are necessary for further advance.
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PMID:The clinical management of soft tissue sarcomas. 141 16

The chemotherapeutic approach to advanced sarcomas of bone and soft tissue is reviewed. The most active single agents against osteosarcoma are doxorubicin (overall response rate, 21%), methotrexate (30% to 40%), cisplatin (25%), and ifosfamide (28%). Current multimodality treatment for Ewing's sarcoma consists of combination chemotherapy with doxorubicin, vincristine, and cyclophosphamide (or ifosfamide in current trials) prior to and concurrent with radiation therapy for the involved bone. In soft tissue sarcomas, doxorubicin is the most active single agent, with overall response rates ranging from 15% to 35%. Dacarbazine has a single-agent response rate of 16%. Ifosfamide has documented activity in sarcoma patients who have failed treatment with doxorubicin-containing regimens. The combination regimen currently producing the highest response rates in soft-tissue sarcomas is doxorubicin/dacarbazine/ifosfamide. Doxorubicin and dacarbazine should be administered by continuous infusion to reduce the severity of nausea and vomiting and the risk of cardiotoxicity. Ifosfamide can be given by continuous infusion or in divided doses with mesna to mitigate urothelial toxicity.
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PMID:Chemotherapy of advanced sarcomas of bone and soft tissue. 148 69

This paper reviews current approaches to the use of ifosfamide/mesna alone or in combination with other agents or modalities in the treatment of pediatric malignancies. Included are data from current or recently completed studies conducted by major pediatric oncology cooperative groups and large individual oncology centers for patients with newly diagnosed or recurrent tumors. Sarcomas, neuroblastoma, lymphomas, recurrent solid tumors, brain tumors, and acute lymphoblastic leukemia are discussed. Randomized trials to determine the relative efficacy of ifosfamide and cyclophosphamide in various childhood malignancies are under way. The long-term consequences of ifosfamide in survivors of childhood cancer, in terms of development of bladder cancer or other malignancies thought to be associated with alkylating agents, are not known, and will only be determined through follow-up studies of adult survivors. Ifosfamide's future role in pediatric oncology will depend on evaluation of its therapeutic benefits against long-term toxicity.
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PMID:Current studies of ifosfamide for pediatric solid tumors and leukemia in the United States. 148 74

The results of several studies of chemotherapy in treatment of soft tissue sarcomas of adults (except embryonic rhabdomyosarcoma) are presented. Most of these studies have been performed and published by the EORTC Bone and Soft tissue sarcoma group. In advanced disease, a randomized trial including 551 evaluable patients and comparing doxorubicin alone (75 mg/m2 q. 3 weeks), and two combination regimens: DI (Doxorubicin (50 mg/m2) + Ifosfamide (5 g/m2 + mesnum q. 3 weeks), and Cyvadic (Doxorubicin 50 mg/m2 d1, DTIC 750 mg/m2 d1, VCR 1.5 mg/m2 d1 (maximum 2 mg/m2), Cyclophosphamide 500 mg/m2 d1 q. 3 weeks), failed to prove any significant difference between these 3 treatments for response rate (25%, 31%, 28%), quality of the response and survival. There is a dose/effect relationship doxorubicin, it is possible that if combination is not superior to a single agent, the reason could be that the dose of doxorubicin is too low when used in combination as compared with the dose when used alone. So, in a phase II trial including 48 evaluable patients, optimal dose of doxorubicin (75 mg/m2 and Ifosfamide (5 g/m2) was given in association with rhGM-CSF. The response rate observed with this combination was 50%. For localized disease, in a randomized trial of the EORTC including 374 evaluable patients with resectable tumors with a mean follow-up of 44 months, the interest of 8 Cyvadic as adjuvant chemotherapy after adequate locoregional treatment (surgery with or without radiotherapy) was demonstrated only for locoregional relapse free survival but no for metastatic disease free survival or overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chemotherapy of soft tissue sarcoma in adults]. 180 96

The dose-limiting toxicity in two separate phase I trials of the high-dose single agents ifosfamide and carboplatin was renal insufficiency at 18 g/m2 and hepatic and ototoxicity at 2,400 mg/m2, respectively. In this phase I study, 16 adults were treated with ifosfamide at 75% of the single-agent maximum-tolerated dose (MTD) (12 g/m2) and escalating doses of carboplatin (400 to 1,600 mg/m2) to determine the nonhematologic dose-limiting toxicity and the maximum-tolerated dose of the combination. Both drugs as well as mesna for uroprotection were given by continuous infusion over 4 days with an additional day of mesna (total dose per course, 15 g/m2). Autologous bone marrow support was stipulated for subsequent dose levels once granulocytes remained less than 500/microL for more than 14 days in two of three to five patients entered at a given dose level. Autologous bone marrow support was used at doses above the 400 mg/m2 carboplatin dose level. At the maximum-tolerated dose level of 1,600 mg/m2 of carboplatin, renal toxicity precluded further dose escalation. Of the five patients entered at this dose level, reversible creatinine elevation greater than 2 mg/dL (median peak, 2.6 mg/dL) was observed in three patients, and irreversible renal failure occurred in an additional patient (peak creatinine, 6.9 mg/dL. Transient gross hematuria appeared more common with the combination than with ifosfamide alone. Two patients developed severe somnolence and confusion associated with a rising creatinine. There were two complete (CRs) and four partial responses (PRs) in 14 heavily pretreated assessable patients (including four partial or complete responses in eight assessable patients with advanced refractory sarcoma, and one CR in two patients with germ cell carcinoma). Carboplatin and ifosfamide appear to have overlapping renal toxicity. Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity. Ifosfamide and carboplatin are an attractive core combination for further studies in the treatment of sarcoma, germ cell, ovarian, and lung carcinomas.
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PMID:A phase I study of high-dose ifosfamide and escalating doses of carboplatin with autologous bone marrow support. 184 7

Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose level if granulocytes were more than 500/microL for more than 14 days in two of two to five patients at a given dose level. Doses were escalated from 8 to 18 g/m2 ifosfamide. Mesna was given at an equivalent dose by continuous infusion for 5 days. At the 18 g/m2 dose level, dose-limiting renal insufficiency and a median of 11 days (range, 8 to 18 days) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion ws not used. The duration of myelosuppression, the frequency and severity of mucositis, and renal tubular acidosis were all dose-dependent. Mild to moderate CNS toxicity also appeared to be related to dose; however, severe CNS toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. Transient hematuria (greater than 50 red blood cells [RBCs]/high power field) occurred once but did not affect treatment. There were nine responses (two complete) in 27 heavily pretreated assessable patients including seven responses in 20 patients with advanced refractory sarcoma. Ifosfamide with mesna uroprotection can undergo considerable dose escalation over the usual prescribed doses before nonhematologic dose-limiting toxicity is encountered. Ifosfamide has broad cytotoxicity against solid tumors and may prove to be an important addition to high-dose combination chemotherapy regimens.
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PMID:High-dose ifosfamide with mesna uroprotection: a phase I study. 210 23

In two sequential trials, 154 patients were treated with dosages of ifosfamide, ranging between 8 and 18 g/m2 divided over 4 days, with mesna uroprotection. The first was a phase II efficacy trial in 125 advanced sarcoma patients (Antman et al: J Clin Oncol 7:126-131, 1989), while the second was a dose escalation trial involving 29 patients (Elias et al: J Clin Oncol 8:170-178, 1990). In the first trial, patients received 8 to 10 g/m2 ifosfamide either by bolus or continuous infusion. The response rate for the 64 patients receiving bolus administration was 23% compared with 12% for the 60 patients receiving a continuous infusion schedule (P = .09). Of the 154 patients, 144 had sarcoma and had failed at least one previous regimen. Of these 144, 4% responded completely and 23% had a complete or partial response. The maximum tolerated dose of ifosfamide was 16 g/m2 in the second trial. Dose-limiting renal toxicity was observed at 18 g/m2 ifosfamide (Elias et al: J Clin Oncol 8:170-178, 1990). The duration of myelosuppression and the frequency and severity of mucositis and renal tubular acidosis were dose-dependent. A median of 11 days (range, 8 to 18) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion was not required. Severe central nervous system toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. The first four patients on the standard-dose study did not receive mesna because it was unavailable; three developed gross hematuria. In patients who received mesna, hematuria was uncommon. Hematuria in the group as a whole was significantly associated with a lack of uroprotection, but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus versus a continuous infusion schedule. Patients receiving ifosfamide with mesna uroprotection can tolerate considerable dose escalation over the usual prescribed doses before nonhematologic toxicity becomes dose-limiting. Ifosfamide, with its broad activity in solid tumors, may prove to be an important addition to high-dose combination-chemotherapy regimens (Elias et al: J Clin Oncol 8:170-178, 1990).
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PMID:Ifosfamide and mesna: response and toxicity at standard- and high-dose schedules. 211 Mar 86

Ifosfamide and cyclophosphamide have many toxicities in common. Interstitial pneumonitis has not been reported previously as a side effect of ifosfamide therapy. The authors report the case of a 58-year-old woman who was treated with ifosfamide for soft tissue sarcoma. After the fifth cycle of chemotherapy she developed clinical evidence of interstitial pneumonitis, a diagnosis that was later confirmed at autopsy. The authors suggest that ifosfamide therapy was directly related to this patient's fatal case of interstitial pneumonitis.
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PMID:Interstitial pneumonitis associated with ifosfamide therapy. 211 39

Ifosfamide, an analogue of cyclophosphamide, has been proven to be of value in numerous malignancies, including testicular cancer, sarcoma, and lymphoma. Furthermore, ifosfamide is more suitable for combination chemotherapy than its parent compound because it causes less myelosuppression than cyclophosphamide. There have been only a few studies evaluating single-agent ifosfamide in small cell lung cancer (SCLC). In patients who have had little or no prior chemotherapy, ifosfamide appears as active as any single agent. Combination chemotherapy regimens employing cisplatin (or carboplatin) plus etoposide plus ifosfamide are currently under way on both sides of the Atlantic. A Hoosier Oncology Group (HOG) study will evaluate this three-drug regimen v cisplatin plus etoposide, and this protocol will establish or refute the value of ifosfamide as first-line therapy in extensive SCLC.
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PMID:Ifosfamide in small cell lung cancer. 253 44

The role of chemotherapy in adult soft-tissue sarcomas is controversial. In this review, the author examines the effectiveness of single-agent and combination chemotherapy to manage advanced disease and the role of adjuvant combination chemotherapy to control primary tumours and prevent the spread of the disease. Doxorubicin (Adriamycin) is still considered the most effective single agent for advanced soft-tissue sarcoma. Ifosfamide has given similar results and may have greater potential in combination therapy than cyclophosphamide. A current study using trimetrexate shows early positive results. Doxorubicin, cyclophosphamide, vincristine and dacarbazine is currently the most efficacious combination. The efficacy of adjuvant chemotherapy remains to be established. The majority of studies indicate some benefit with chemotherapy, particularly in the relapse-free survival rate, but no consistent improvement in overall survival has been noted.
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PMID:Current perspectives in the management of soft-tissue sarcoma. The role of chemotherapy in multimodality therapy. 305 63


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