Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 409 sufferers from various malignant tumours, we used the cytostatic Ifosfamide (ASTAZ4942) in fractionated doses. The total i.v. dose averaging 300 mg/kg bodyweight, was either spread over 5 consecutive days (5 X 60 mg/kg i.v.) or over 10 consecutive days (10 X 30 mg/kg). At the same time, most patients were irradiated, the radiation dose usually being only one tenth the antitumour dose. Infections and electrolyte imbalance were first treated before Ifosfamide therapy was instituted. Cases of advanced cerebral sclerosis, thrombopenia below 75,000/cmm, cerebral metastases, impaired renal function and inadequate cooperation of the patient were excluded from the studies. To prevent and control side effects, various premedications and adjuvants are required: Antiemetics, prevention of cystitis and infections, cardiovascular agents etc. Corticosteroids are contraindicated. Out of 360 assessable patients 101 had a full remission, 150 a partial remission, 79 were failures; 30 cases were not evaluated. Good results were seen especially in ovarian carcinoma, mammary carcinoma and microcellular bronchial carcinoma. Particularly striking is the drug's effectiveness in testicular tumours including teratomas, osteosarcomas, chondrosarcomas and myosarcomas as well as in some adenocarcinomas of the gastro-intestinal tract, particularly pancreatic carcinoma. In lymphoreticular tumours and haemoblastoses, its potency is less pronounced. The side effects of Ifosfamide are the same as those of other alkylating agents. They are reversible and can usually be controlled or even avoided by adequate preventive measures. In the order of incidence we observed: Alopecia, leukopenia, fall in haemoglobin, cystitis, intercurrent infections, nausea and vomiting as well as cerebral disorders. Since haemorrhagic cystitis considerably interferes with Ifosfamide treatment, its prevention is of essential importance. Because of possible complications and specific premedication and adjuvant measures for their control, this type of treatment should for the present only be carried out by oncologists or special cancer centres.
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PMID:Results obtained with fractionated ifosfamide massive-dose treatment in generalized malignant tumours. 78 66

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 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

Thirty-seven patients with widely metastatic malignant melanoma were treated with one of three chemotherapy regimens, incorporating high-dose dacarbazine (DTIC). The chemotherapy was followed by autologous bone marrow rescue which was harvested under local anesthesia in 25 of the patients. The three regimens comprised a 24-hour infusion of DTIC (Regimen A for patients less than 45 years of age, 4.3 to 10.5 g/m2; B, if greater than 45 years of age 2.7 to 4.0 g/m2; and later C, if greater than 45 years of age 7.0 to 8.0 g/m2). The second alkylating agent was given at +8 and +16 hours from the start of DTIC. The total doses of the melphalan ranged from 60 to 130 mg/m2 for Regimen A and 30 to 40 mg/m2 for Regimen B. Ifosfamide 5.0 to 8.0 g/m2 was given instead of melphalan in Regimen C. The response rates for the regimens were 81% (25% CR) for A, 27% (11% CR) for B, and 20% (with no complete responders) for Regimen C. There was no statistically significant difference between the three regimens for survival with a median value of 6 months. One of the 16 patients treated with the very high dose Regimen A died of septicemia and three of ten patients in Regimen C died within the first 2 weeks of treatment. There was statistically significant greater myelosuppression, stomatitis, and diarrhea in the very high dosage DTIC and melphalan (Regimen A) compared with the other two regimens. No significant difference in response rate or toxicity was observed for the different dosages escalated within each of the three regimens. Although hematologic and gastrointestinal toxicity were very severe, no unusual side effects were noted except for one episode of severe acute renal failure in the high-dose DTIC and melphalan, Regimen A. Responses occurred mainly in nonvisceral, nodal, and cutaneous sites and occasionally in pulmonary metastases. The Karnofsky performance improved 4 to 6 months after treatment notably with the high-dose DTIC and melphalan therapy. No survival benefit for the combination chemotherapy despite the high dosages was detected and such an approach currently cannot be recommended.
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PMID:High-dose, double alkylating agent chemotherapy with DTIC, melphalan, or ifosfamide and marrow rescue for metastatic malignant melanoma. 264 5

In a phase II study, 16 adult patients with locally advanced or metastatic soft tissue sarcomas were treated with i.v. infusions of ifosfamide/mesna 5 g/m2 plus i.v. doxorubicin 40 mg/m2. Courses were given every 3 weeks up to a maximum of six courses in responding patients. Six patients (37.5%) had either complete (1 patient) or partial responses (5 patients). Confidence limits for this response rate were 15.2%-64.5% (95% confidence level). There was one toxic death in association with encephalopathy, renal and bone marrow failure. Unilateral pneumothoraces occurred in 2 patients with large pulmonary metastases. Recurrent severe ifosfamide/mesna encephalopathy occurred in 2 patients at risk for this complication; patients who develop severe ifosfamide/mesna encephalopathy should not be retreated with this drug. Ifosfamide/mesna with doxorubicin is an active combination to treat adult soft tissue sarcoma but, despite the feasibility of the combination, sequential monotherapy with these drugs might provide similar or better clinical benefit.
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PMID:A phase II study of ifosfamide/mesna with doxorubicin for adult soft tissue sarcoma. 312 71

Ifosfamide (IFOS) 5 g/m2 and its parent analog Cyclophosphamide (CYCLO) 1.5 g/m2 were studied in a randomized phase II study, accruing 171 patients with advanced soft tissue sarcoma. Both drugs were administered as 24 hr infusions, every 3 weeks, with comcomitant Mesna 400 mg/m2 i.v. bolus 4 hourly X 9 doses. Twenty-four patients were ineligible and 12 were not evaluable. The groups were well matched for age, previous chemotherapy (42% of the total) or radiotherapy, the presence of distant metastases and performance status, but there were more females (59% vs. 45%) in the IFOS arm. Among the 68 evaluable patients receiving IFOS, there were 2 CR, 10 PR (overall response 18%), 27 SD and 29 PD. For CYCLO, the corresponding results in 67 patients were 1 CR, 4 PR (overall response 8%), 23 SD and 39 PD. Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively. Response rates were higher for females (20% vs. 5%, P = 0.01) and patients who had not received previous chemotherapy (19% vs. 4%, P = 0.01). Fourteen of the 17 responses came from a group of 43 females, who had not received previous chemotherapy, for whom the overall response rate was 37.5%. Remissions were noted in only 4 histological subtypes (centrally reviewed material), i.e., 5 of 17 synovial sarcomas, 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas. One of the 31 leiomyosarcomas responded to Cyclophosphamide. Durations of response did not differ significantly between the 2 arms--median 26, range 10-81+ weeks. Leucopenia was significantly more severe on CYCLO, particularly in patients who had received previous chemotherapy (P = 0.007). Serious infections occurred in approx. 7% of patients with no difference between the two drugs, although there was one toxic death on CYCLO. Nausea and vomiting were significantly worse on IFOS and alopecia, related in extent to dose, was seen in both arms. Other side-effects, such as hematuria or rises in serum creatinine and encephalopathy, were infrequent and mild. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy.
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PMID:Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas. 359 91

Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). The commonest sites were lower limb (33%), visceral (21%), trunk (13%), retroperitoneum (12%) and upper limb (10%). Leiomyosarcoma (27%), liposarcoma (14%) malignant fibrous histiocytoma (10%) and neuro plus fibrosarcomas (15%) were the most frequent histological subtypes. A high proportion of uterine sarcomas (17%) is a point of distinction from many other series. Histological grade was specified in 72% of cases and the distribution (Grade I--27%; II--6%; III--67%) reflected a referral bias towards advanced disease. Local resection of the primary tumour was performed in 76% of cases. In many instances this only amounted to 'shelling out' and true compartmental excisions were rare. Amputation was performed in 31% of patients with limb sarcomas. Ninety-eight patients (38%) had experienced one or more local recurrences prior to referral and the overall local recurrence rate was 56%. Suitable patients (78%) received chemotherapy, 50% entering multicentre trials in collaboration with the EORTC. The commonest regime used in patients with advanced disease was CYVADIC which produced an overall response rate of 37%. Ifosfamide, used as a single agent in 16 patients, induced 3CR and 5PR for an overall response rate of 50%. When used in combination with MTX and VADIC, there was no difference in response rate, but numbers in these pilot studies were small. Seventeen high risk patients received adjuvant chemotherapy with VAC, but the results (11 relapses) were disappointing. An EORTC trial, comparing adjuvant CYVADIC chemotherapy with control has accrued 307 patients, 49 of these from the Christie Hospital. Preliminary results within this centre - 13/25 relapses in the control arm, 5/23 in the chemotherapy arm-suggest an advantage for chemotherapy but the data are statistically not significant. Post-operative radical radiotherapy after resection of the primary tumour or local recurrence was performed in 51 patients, with local control in 65% of cases, although metastases developed in 41%. At the time of analysis (1st April 1984) 98 (38%) were alive, of whom 72 showed no evidence of disease and 52 had never relapsed. Malignant disease was the cause of death in 92%. Overall survival was not influenced by sex, but patients less than 40 years of age fared significantly better (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combined modality management of local and disseminated adult soft tissue sarcomas: a review of 257 cases seen over 10 years at the Christie Hospital & Holt Radium Institute, Manchester. 397 Aug 10

Advanced malignant testicular tumors can be treated very successfully by chemotherapy. The most effective 3 or 4-drug combinations contain CisPlatin, Vinblastine, Bleomycin, Adriamycin, Cyclophosphamide, Ifosfamide and Vepesid. Complete remissions of 60% can be obtained; depending on histology, frequency of metastases, and former radiation therapy. Resection of residual pulmonary or retroperitoneal metastases render an additional 10-20% of the patients free of tumor. Side effects following chemotherapy should not be neglected: Depression of bone marrow, severe vomiting, alopecia, and azoospermia.
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PMID:[Modern chemotherapy of a malignant testicular tumors (author's transl)]. 617 87

Ifosfamide (Z 4942) is an alkylating agent with the structure of a cyclophosphamide analog. Preliminary studies performed in our hospitals demonstrate the releasing effect of Ifosfamide for persistent pain caused by metastases of the prostatic cancer at various regions. Ifosfamide was given 2 grams a day intravenously with hydration and alkalization for consecutive 5 days. The regimen was performed every 3 or 4 weeks. Pain has disappeared in 7 of 10 cases within 2 or 3 courses. Pain of other 3 cases has also greatly reduced. The effective rate for the primary lesion of the prostatic carcinoma in stage C and D is 30.7%. Side effects were nausea, vomiting, hair loss and leukopenia.
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PMID:[Treatment of pain caused by metastases of reactivated prostatic cancer with ifosfamide]. 663 95

The successful treatment of metastases will have to include modalities that can overcome the obstacles presented by the heterogeneous nature of malignant neoplasms and the continuous evolution of variant cells. Macrophages activated to become tumoricidal by interaction with L-MTP-PE may be able to accomplish this. Osteosarcoma appears to be an ideal disease in which to employ L-MTP-PE as an additional adjuvant to present chemotherapy regimens. The lung is the most frequent site of metastases, and pulmonary micrometastases are considered to be present in the majority of patients at diagnosis. Approximately 40% of patients with osteosarcoma develop pulmonary metastases despite the administration of adjuvant chemotherapy. The 2-year disease-free interval has not improved over the past 10 years, despite multiple changes in adjuvant regimens. These data argue that there is a subpopulation of patients who harbor tumor cells that are relatively resistant to all chemotherapy. Unfortunately, this group of patients cannot be identified at the time of initial diagnosis. This necessitates the incorporation of new forms of therapy into the adjuvant chemotherapy protocols for all patients in the hope of eradicating the resistant cells harbored in the 40%. Based on the data summarized previously, L-MTP-PE may improve the clinical outcome of patients with osteosarcoma by activating pulmonary macrophages to destroy residual tumor cells that are not eliminated by chemotherapy. Monocytes from osteosarcoma patients can be rendered cytotoxic to tumor cells by in-vitro incubation with L-MTP-PE and following the intravenous administration of this agent. L-MTP-PE can be given safely to both adults and children with minimal side effects. The whole-body distribution of 99mTc-labeled liposomes containing MTP-PE confirms that the agent is taken up by the lungs. Biologic activity in osteosarcoma patients is revealed by the elevations in plasma levels of several cytokines plus stimulation of monocyte-mediated cytotoxicity following L-MTP-PE infusion and by histologic changes in the pulmonary lesions. Ifosfamide therapy given in combination with L-MTP-PE does not suppress this immune response, as judged by both plasma cytokine levels and tumor histology. Finally, L-MTP-PE has been shown to be effective as a single agent against relapsed osteosarcoma. It is unlikely that the addition of other chemotherapeutic agents to the adjuvant chemotherapy protocols will alter the 65% to 70% 2-year disease-free survival rate associated with osteosarcoma. The preceding data indicate that L-MTP-PE is an active agent against this disease and deserves further investigation. Therefore, the inclusion of L-MTP-PE with chemotherapy is a reasonable alternative to consider to improve the response rate of this disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. 749 Feb 49


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