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)

A phase IIb trial using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in combination with ifosfamide (IFX) for patients with relapsed osteosarcoma was undertaken to determine (a) the tolerability of the combination therapy, (b) if L-MTP-PE increased the toxicity of IFX, and (c) whether IFX altered or suppressed the in vivo immune response to L-MTP-PE. Patients had histologically proven osteosarcoma and pulmonary metastases that either developed during adjuvant chemotherapy or were present at diagnosis, persisted despite chemotherapy, and recurred following surgical excision. Stratum A patients were rendered clinically free of disease within 4 weeks of study entry prior to receiving combination therapy. IFX was administered at 1.8 g/m2 for 5 days every 21 days for up to eight cycles. L-MTP-PE was administered twice weekly for 12 weeks, then once weekly for 12 weeks. Once cycle of combination therapy was defined as 5 days of IFX and 3 weeks of L-MTP-PE therapy. Stratum B patients had measurable disease at study entry that was judged to be amenable to surgical resection. Stratum B patients received three cycles of combination therapy prior to surgery to judge clinical and histologic response. Postoperatively, patients received an additional five cycles. A total of nine patients were entered into the protocol: six on stratum A and three on stratum B. Serial blood samples were collected and assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha], interleukin-6 [IL-6], IL-8, neopterin, C-reactive protein). In addition, peripheral blood monocyte tumoricidal activity was evaluated pre- and post-combination therapy. Complete blood counts with differential and platelet counts were followed weekly. No increase in the toxic side effects of IFX was demonstrated when administered with L-MTP-PE nor were delays in IFX administration due to neutropenia experienced. The toxic side effects of L-MTP-PE were also not increased. Elevations of serum C-reactive protein, plasma neopterin, IL-6, IL-8, and TNF alpha following combination therapy were similar to those observed in patients treated with L-MTP-PE alone. Monocyte-mediated tumoricidal activity was elevated 24 and 72 h following L-MTP-PE and IFX therapy, similar to what has been reported following L-MTP-PE alone. Tumor specimens obtained from stratum B patients showed the histologic characteristics consistent with a "chemotherapy effect," i.e., dead, amorphous, acellular osteoid with cell drop-out.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combination therapy with ifosfamide and liposome-encapsulated muramyl tripeptide: tolerability, toxicity, and immune stimulation. 761 44

We investigated the pattern and frequency of ovarian metastases in patients with primary gastrointestinal malignancies and evaluated the response to surgery, chemotherapy and in three cases radiotherapy. The literature reports that this group of patients have a poor prognosis, but no report has specifically addressed the response to chemotherapy. Using a database which is generated prospectively, we analysed 51 patients with primary gastrointestinal malignancies and ovarian metastases. All patients received chemotherapy but only 36 were evaluable for response; five had adjuvant treatment and ten had non-measurable disease. Seventeen patients had surgical oophorectomy and three patients received radiotherapy. The overall response rate to chemotherapy was 22%; eight partial responses and no complete responses. When stratified according to site of response, 11 (31%) patients had a partial response at sites of extraovarian metastases and only five (14%) had a partial response in the ovaries. Seven patients with primary colorectal cancer had a differential response in favour of extraovarian sites. The median survival was 9 months for the 51 patients. Three premenopausal women with resected gastric carcinoma received adjuvant chemotherapy and relapsed only in the ovaries. In primary colorectal tumours the response of ovarian metastases to chemotherapy is less than that for other sites. Therefore, the ovary may be a sanctuary site for metastases which has important implications for adjuvant chemotherapy in women. These women could be followed up regularly by transvaginal ultrasonography to detect such metastases at an early stage when they would be amenable to surgical resection. Surgery should be considered for selected patients who develop metachronous metastases, as patients may be rendered disease free for several months.
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PMID:Ovarian metastases from primary gastrointestinal malignancies: the Royal Marsden Hospital experience and implications for adjuvant treatment. 781 57

The Eastern Cooperative Oncology Group (ECOG) is conducting a phase II trial of Taxol in patients with histologically confirmed, advanced squamous cell carcinoma of the head and neck. Patients entered in the study to date either had recurrent disease or were newly diagnosed with incurable local-regional disease or distant metastases. Prior chemotherapy was limited to induction or adjuvant chemotherapy at least 12 months prior to entry in the study. All patients had an ECOG performance status of 0 or 1 and measurable disease. The treatment schedule was Taxol 250 mg/m2 by 24-hour continuous intravenous infusion followed by r-met Hu granulocyte-colony stimulating factor 5 micrograms/kg/day subcutaneous injection day 3 to 15 or until the absolute neutrophil count was greater than 1500. Cycles were repeated every 3 weeks. As of September 1, 1992, 27 patients were registered in the study. Of these, three patients were determined to be ineligible, and three were too early to evaluate. There were two early deaths, one definitely and one possibly drug related. Two complete and five partial responses have been observed. Twenty-three patients receiving 83 courses were evaluable for toxicity. Myelosuppression was the primary toxicity observed with 17 (74%) patients experiencing grade 3 or 4 leukopenia and with 20 (87%) patients experiencing grade 3 or 4 neutropenia lasting an average of 2 days (range, 1-4). Peripheral neuropathy occurred in nine patients (grade 1, five patients; grade 2, three patients; grade 3, one patient). Other infrequent toxicities were stomatitis, nausea and vomiting, and myalgias. This trial will continue until 30 eligible patients are accrued.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II evaluation of Taxol in advanced head and neck cancer: an Eastern Cooperative Oncology group trial. 791 24

Dacarbazine (DTIC) exerts its major biochemical effect through the formation of methylated DNA adducts. Hydroxyurea (HU) is a ribonucleotide reductase inhibitor which blocks DNA excision-repair by the depletion of intracellular ribonucleotides. Combination of HU and DTIC was used to enhance the activity of DTIC by inhibiting DNA repair. 16 patients with metastatic malignant melanoma were treated with the combination. All patients had measurable disease and none had received prior systemic therapy. Hydroxyurea was given as a continuous intravenous (i.v.) infusion of 1 g/h (total 36 g) and DTIC 1 g/m2 i.v. over 1 h, 23 h from the start of hydroxyurea infusion. 4 patients achieved partial remission with an objective remission rate of 25% [95% confidence interval (CI) 7-52%]. Median duration of response was 3.5 months. 3 of the responding patients had predominant visceral metastases. Disease was stabilised in 5 patients with a median time to progression of 16 months. The predominant toxicity to this treatment was gastrointestinal, with 3 patients developing grade 3 nausea/vomiting. Only 1 patient developed grade 3 leucopenia complicated by septicaemia. It is concluded that the combination of hydroxyurea and DTIC is a well-tolerated regimen with activity against visceral metastases from malignant melanoma but the duration of response to this treatment is short.
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PMID:A phase II study of high-dose hydroxyurea and dacarbazine (DTIC) in the treatment of metastatic malignant melanoma. 794 68

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0-2, a life expectancy of > or = 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m2 VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m2). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR + PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of < 1,000/mm3. Grade 2-3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone.
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PMID:Vincristine with high-dose etoposide in advanced breast cancer: a phase II trial of the Piedmont Oncology Association. 798 95

This study investigated the toxicity and efficacy of busulfan-containing pre-transplant regimens in patients with solid tumors. The majority of these patients were also treated on protocols involving two transplant courses aiming at further reducing tumor burden. Between October 1984 and November 1993, we treated 44 patients with recurrent breast cancer (n = 28), sarcoma (n = 10) or ovarian cancer (n = 6) with one of two busulfan-containing regimens. All patients except two had measurable disease prior to transplantation. Twenty-one patients had not received chemotherapy for metastatic disease. Of the remaining 23 patients treated with standard-dose chemotherapy, 14 had progressive disease. Busulfan 16 mg/kg was paired with cyclophosphamide 200 mg/kg (BuCY) or with etoposide 60 mg/kg (Bu-Vp). The Bu-Vp combination (32 courses) was used as the second preparative regimen in patients who had received thiotepa, carboplatin and cyclophosphamide for their first transplant. The BuCY regimen was used in 16 courses, either for single or for tandem transplant. Bone marrow cells only were used in 17 transplants and peripheral blood progenitor cells, with or without bone marrow, in 31 courses. Treatments were usually well tolerated. Common toxicities included mucositis, skin rash and veno-occlusive disease of the liver (fatal in two). One patient developed generalized seizures during busulfan therapy. Hematologic recovery was significantly accelerated with peripheral progenitor cells and permitted the administration of closely spaced tandem transplants. Two patients receiving sequential transplants with BuCY experienced severe long-term neurologic and pulmonary toxicity. Objective responses were noted in 26 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Busulfan-containing pre-transplant regimens for the treatment of solid tumors. 799 69

Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desmoplastic infantile gangliogliomas: an approach to therapy. 800 54

Twenty-two patients with metastatic breast carcinoma were treated with a combination of cisplatin (100 mg/m2 i.v. day 1) and etoposide (100 mg/m2 i.v. days 1-3). Eligible patients had measurable disease with normal organ functions, performance status < 3, age < 70 years and no previous chemotherapy for metastatic disease. Twenty patients were assessable for response. Objective responses were seen in 50% (95% confidence limits: 24.4-67.8). One patient achieved a complete response. Objective response was observed in patients with visceral metastatic disease and who had received anthracyclin-containing regimens in previous chemotherapy. Median survival after therapy was 55 weeks. Median time to progression was 23 weeks. Hematologic toxicity was limiting. Cisplatin plus etoposide is an active combination in advanced breast cancer.
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PMID:Phase II trial of cisplatin and etoposide as first-line therapy in metastatic breast carcinoma. 820 20

Twenty-seven women with metastatic breast cancer (at least one site of measurable disease) entered a phase II study of chronic oral etoposide (50 mg/m2/day x 21 days, given every 4 weeks). To date, 23 patients are evaluable for response and toxicity. All patients had received prior chemotherapy (adjuvant therapy, one patient; adjuvant plus chemotherapy for metastases, six patients; chemotherapy for metastases, 16 patients). Thirteen patients had previously received anthracyclines, and 10 had also received prior hormonal therapy. Of the 23 evaluable patients, one obtained a complete response and six achieved partial responses (objective response rate 30.4%, 95% confidence interval, 13 to 53%). Responses were seen in lymph nodes (three of eight sites), skin and soft tissue (five of seven), lung (two of six), lytic lesions of the bone (one of three), and liver (1 of 12). The median duration of responses was 6 months (range, 1+ to 8). The main toxic side-effects were leukopenia (74% of patients), thrombocytopenia (22%), and anemia (69.5%). Myelosuppression in four patients (17%) necessitated a 25% dose reduction. Other toxicities included alopecia (83%), mucositis (52%), and emesis (35%). Chronic oral etoposide appears to be an active regimen in metastatic breast cancer patients previously exposed to chemotherapy.
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PMID:Preliminary results of a phase II trial of chronic oral etoposide in breast cancer. 822 16

In chemofiltration a large dose of a cytotoxic drug is infused into an artery supplying a cancerous area, thus limiting systemic toxicity. The venous return from the area is pumped into a chemofiltration unit at 750 ml/min and the drug is filtered out of the blood, which is then returned to the systemic circulation. Of 22 patients with locally advanced cancer, systemic chemotherapy had failed in 63%. 9 of them underwent chemofiltration of the liver for advanced metastatic cancer of the colon (4 cases), rectum (2), breast (2) and ovaries (1); and 13 underwent chemofiltration of the pelvis for advanced cancer of the rectum (5), malignant melanoma (5), ovaries (1), cervix uteri (1) and vulva (1). The following drugs were used: 5-FU (750 mg/m2/10 min) and mitomycin-C (30 mg/m2/10 min) for colorectal, ovarian and breast carcinomas; melphelan (1 mg/kg/20 min) or cisplatinum (200 mg/m2/30 min) for malignant melanoma or ovarian carcinoma; mitomycin-C or bleomycin (50 mg/m2/10 min) for carcinoma of the cervix or vulva. 1 patient with extensive liver metastases died of respiratory failure 28 days after the procedure. Surgically related complications occurred in 16% and included wound hematoma (2 cases), infection (1) and venous thrombosis (1). Drug-related complications occurred in 50%, and included transient leukopenia (9), mild renal failure (1), hair loss (2) and prolonged paralytic ileus (1). Partial remission was observed in 10/20 patients who had measurable disease. Time to progression was 5.4 months (range: 4 weeks to 20 months). Stabilization of disease occurred in 7/20 (35%), while in 3 the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chemofiltration for locally advanced cancer]. 834


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