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)

Between 1968 and 1980, 107 consecutive patients with Ewing's sarcoma of bone were entered on three sequential combined modality treatment protocols (S2, S3, S4) at the National Cancer Institute (NCI). Protocol treatment involved 4 cycles of two drug [cyclophosphamide (CTX) and vincristine (VCR)] or three drug [CTX and VCR with either actinomycin-D (ACT-D) or doxorubicin (ADR)] regimens and local irradiation (50 Gy) to the involved bone. Eighty patients presented with localized disease and 27 patients had metastatic disease at presentation, including 11 patients with multiple metastatic sites. With a median potential follow-up of greater than 15 yrs (range 8-20 yrs), 28 pts (27%) remain alive. Disease-free (DFS) and overall survival (OS) decreased most rapidly during the initial 5 yrs of follow-up with 5-yr DFS of 29% and 5-yr OS of 39%. Only two patients with metastases at presentation are long term (greater than 5 yr) survivors. For localized disease patients, the 2, 5, 10, and 15 yr DFS and OS are 52%, 37%, 35%, and 33% DFS and 68%, 51%, 39%, and 34% OS, respectively. Eleven patients relapsed locally as the first site of failure. Using the Cox proportional hazards model, four significant variables for both DFS and OS were recognized, including metastatic disease at presentation, age greater than 25 yrs, high LDH in localized disease patients, and central primary tumor in localized disease patients in decreasing order of significance. We conclude that a majority of these patients with Ewing's sarcoma of bone relapsed within 5 yrs of presentation although late relapse (5-15 yrs) did occur. Local failure occurred in 20% of patients using these combined modality treatments but had no impact on overall survival.
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PMID:Long-term follow-up of Ewing's sarcoma of bone treated with combined modality therapy. 199 54

Melanoma antigen vaccines are a conceptually attractive approach to prevent or delay disease recurrence in patients with surgically resected malignant melanoma. However, the immunogenicity of current vaccines is relatively low. Cyclophosphamide, when given in low doses prior to antigen exposure, is an immunomodulator which has been shown to enhance both humoral and cellular antitumor responses in animals and humans. We conducted a prospective, randomized, clinical trial to study whether pretreatment with cyclophosphamide augments the immunogenicity of a polyvalent, allogeneic, melanoma antigen vaccine in patients with melanoma and low tumor burden. Forty-five patients with resected stage II melanoma (regional metastases) were randomly allocated to treatment with melanoma vaccine or melanoma vaccine plus cyclophosphamide. All patients received the same dose and schedule of vaccine immunizations; those randomized to cyclophosphamide received 300 mg/m2 i.v. 3 days prior to each vaccine immunization. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) skin reactivity to a test dose of vaccine at baseline (prior to treatment) and following the fourth immunization. Humoral immune responses were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of indirect immunoprecipitates of patients' sera at the same time points. Twenty-four patients were randomized to cyclophosphamide pretreatment and 21 to vaccine alone; 22 and 18 patients were evaluable in each group, respectively. Differences were statistically nonsignificant with respect to either cellular (DTH) or humoral (antibody) responses between the two groups. DTH responses were induced in 16 of 22 (73%) and 15 of 18 (83%) patients treated with cyclophosphamide plus vaccine and vaccine alone, respectively. The mean posttreatment augmentation in DTH response in the cyclophosphamide group was 9.5 mm, compared with 9.9 mm in the vaccine-only group. Eight of 12 (66%) cyclophosphamide-pretreated patients and 9 of 12 (75%) vaccine-only patients produced increased titers of antimelanoma antibodies following treatment. No differences were observed between the groups in disease-free or overall survival. In summary, low-dose cyclophosphamide pretreatment failed to augment the immunogenicity of a polyvalent, allogeneic, melanoma vaccine in patients with completely resected early-stage melanoma.
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PMID:Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine. 206 22

Previously we have demonstrated that the in vitro generation of P815-specific anti-tumor cytotoxic T lymphocytes (CTL) was suppressed by splenic suppressor T cells from late tumor-bearing hosts (TBH). Suppression is not caused by in vitro growth of P815 from splenic metastases, since suppression was also seen with spleen cells from late TBH mice bearing a hypoxanthine/aminopterin/thymidine-sensitive subline (PHS-5) of P815 in the presence of HAT. Cyclophosphamide has been shown to inhibit the induction of suppressor cells selectively in a number of immune responses, but evidence that it can inhibit active tumor-induced suppressor T cells is limited. We have found that suppressor T cells already induced by P815 in syngeneic late TBH are sensitive to low doses of cyclophosphamide (50 mg/kg) given 1 day before spleen harvest, but the in vitro CTL response of late TBH spleen cells could not be restored by pretreating the mice with cyclophosphamide, even when exogenous interleukin-2 was added to the cultures. Although 50 mg/kg cyclophosphamide did not inhibit the CTL response of spleen cells from mice immunized with P815 + Corynebacterium parvum, the same dose of cyclophosphamide eliminated the CTL response of spleen cells from early TBH. Interleukin-2 (IL-2) did not overcome this effect of cyclophosphamide, suggesting a direct effect on CTL. "Ultra-low" -dose cyclophosphamide (10 mg/kg) did not adversely effect early TBH CTL but was still able to eliminate suppressor T cell activity from late TBH. Nevertheless, late TBH CTL remained unresponsive after pretreatment of mice with ultra-low-dose cyclophosphamide, even when exogenous IL-2 was added in vitro. CTL precursor frequency analyses demonstrated that cyclophosphamide pretreatment had little or no effect on the numbers of CTL precursors from early TBH. Late TBH CTL precursor cells were not detectable in these studies, with or without suppressor T cell inhibition by cyclophosphamide pretreatment. Thus, it appears that most CTL precursor cells may be lost or irretrievably inactivated in the spleens of late TBH mice.
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PMID:Cyclophosphamide and abrogation of tumor-induced suppressor T cell activity. 213 31

Results obtained by the authors and a review of the literature have made them able to point out recent developments in cases of epithelial cancer of the ovary diagnosed in an advanced stage of the disease. This is the most frequent finding when the diagnosis is made and it is most important in assessing the future prognosis to know how far on the disease has progressed. Cancer of the ovary has long been thought of as a peritoneal disease, but all the same 40% of metastases occur further away and the majority of these are in the pleura or the lung and more rarely in the brain; and all these have been observed. The degree of differentiation is another important element for prognosis. Deciding how differentiated tissue is, is relatively subjective. A scoring protocol is suggested to make the assessment more systematic. The grading can be varied according to the response to treatment. A great majority of authorities believe that reduction of the size of the tumour surgically should be the first procedure but how useful this is has never been proved because there has never been any controlled study. It is possible in most cases to reduce the size of the tumour greatly but often this may need removal of some of the intestines with acceptable morbidity. Chemotherapy with Cisplatin, Cyclophosphamide and in the hands of certain authors, Doxorubicine, has been shown to be helpful in 80% of cases and seems to be the most appropriate treatment.
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PMID:[Epithelial cancer of the ovary. Contribution of the experiences of a treatment facility to the current data of prognosis and treatment]. 218 94

A case is described of embryonal rhabdomyosarcoma (E.R.) of the middle ear in a 4-year-old child; survival has been over 9 years. R.E. is the most common malignant tumor of the auricular region in children and is most often fatal due to locoregional extensions or secondary metastases carried through the bloodstream and lymphatic systems. The basis for treatment is a multidisciplinary approach to the disease: surgery with as broad an exeresis as possible; radiotherapy with tumor-killing doses of 5,500/6,000 rads; and polychemotherapy (Vincristina, Endoxan, Methotrexate). Such "aggressive" treatment often results in a high rate of morbidity with complications involving the blood, bones, eyes and meninx often requiring temporary suspension of treatment and prolonged hospitalization.
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PMID:[Embryonal rhabdomyosarcoma of the middle ear: description of a case with long-term survival]. 226 Apr 43

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984. 242 88

The authors report on combination chemotherapy in 22 patients (seven men, 15 women; age 20-67, median 38.5 years) with incompletely resected invasive thymoma. Twelve of 22 patients have had prior radiotherapy of the tumor (four of 12 local failure, eight of 12 remote metastases). By subsequent chemotherapy five of 12 obtained complete remission (CR). One of them died by relapsed tumor, another by an intercurrent infection. At 5 years after diagnosis the survival rate of the 12/22 patients was 33% (Kaplan-Meier). Ten of 22 patients received chemotherapy as primary treatment of incompletely resected thymoma. Four of 10 obtained CR. One of them was lost during follow-up, the others received adjuvant irradiation of the mediastinum and are free of disease. Two of ten obtained partial remission (PR), but relapsed within 6 months after chemotherapy. At 3 years after diagnosis the survival rate of the 10/22 patients was 34%. Thirteen of 22 patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP/bleomycin as first chemotherapeutic regimen. Five of them achieved CR. Cyclophosphamide, vincristine, and prednisone (COP) or COP plus procarbazine (COPP) was administered to six of 22. Three of them obtained a CR and one a PR. In an alternating manner COPP and Einhorn regimens were given to two of 22, one of which had a CR. In one of 22 the doxorubicin, bleomycin, cisplatin, prednisone (BAPP) regimen was followed by a PR. The authors conclude that combination chemotherapy is effective in the first-line postsurgical treatment of incompletely resected thymoma and also in the treatment of local or metastatic relapses after radiotherapy.
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PMID:Chemotherapy of invasive thymoma. A retrospective study of 22 cases. 246 48

We treated a 66-year-old Japanese woman with malignant mixed mesodermal tumour of the heterologous type arising from the paracolic peritoneum. The tumour contained heterologous elements in the form of cartilage in addition to carcinosarcomatous areas. This is the third case of malignant mixed mesodermal tumours originating from the peritoneum to be documented in the literature. A complete resection of the tumour was carried out but multiple lymph nodes metastases in the left neck occurred 5 months later. Cyclophosphamide in doses of 150 mg daily by mouth was initiated, with the result of a complete regression of the malignant lesions. She died of myocardial infarction 21 months after surgery.
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PMID:Malignant mixed mesodermal tumour of the peritoneum with a complete response to cyclophosphamide. 254 65

A 53 year old male was admitted with cough, chest pain and bloody sputa for one month. His admission chest radiography revealed a tumor shadow in right hilus. The patient was diagnosed as small cell lung cancer (oat cell type) by transbronchial biopsy. Clinical staging was IIIA and performance status was 1. The patient was treated by combined chemotherapy (CPA, ADM and VCR) for 3 courses and chest irradiation (5,000 rad). After such therapy, the primary site was regressive until 2 months prior to death. One month after irradiation, abdominal CT showed multiple liver metastases. Though CDDP 100 mg/body and etoposide 100 mg/body X5 were administered systemically, improvement of metastases of the liver was not revealed by abdominal CT. However, after hepatic arterial infusion of ADM (10 mg/body) suspended in a lipiodol (3 ml/body) and CDDP (100 mg/body) was performed, liver metastases were remarkably regressive by abdominal CT. The patient died of a systemic relapse about 14 months after liver involvement.
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PMID:[A case of intra-arterial infusion chemotherapy in small cell lung cancer with liver metastases]. 255 17

Studies were carried out on the combination of Cimetidine (CMTD) with Cytoxan (CTX) in three murine tumors. While the combination significantly potentiated the anticancer effect of CTX in L1210 leukemia, the results with P388 leukemia were not significantly different. The results with Lewis Lung Carcinoma showed a consistent reduction in the number of metastases. However, there was no consistent concomitant prolongation in survival. The host strain, biology of the tumour and the drug used in combination with CMTD might be some of the factors responsible for the varied response.
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PMID:Effects of cimetidine combination with cyclophosphamide in transplanted murine tumors. 259 43


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