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)

Twenty-five patients with metastatic and/or recurrent nasopharyngeal carcinoma were treated with cisplatin 20 mg/m2/day on days 1-5 i.v. with hydration; 5-fluorouracil (5-FU) 1,000 mg/m2/day by continuous infusion (CI); and bleomycin 15 mg/m2 on day 1 also by CI. These cycles were repeated every 4 weeks. Twenty-three (92%) had distant metastases. Bone was the most frequently involved site (72%), followed by lungs (44%) and liver (40%). More than half the patients (14/25) presented with at least 3 organ sites involved or had local T3/T4 or N3 lesions with a distant metastasis. The median time from relapse to start of chemotherapy was 7.5 months. We observed 1 (4%) complete response (CR), and 9 (36%) partial responses (PR). The objective response rate (CR + PR) was 40%. Hematologic toxicities were frequently encountered. Twenty (80%) patients experienced leukopenia during the treatment courses and 9 (36%) had severe (grade 3 or 4) leukopenia. Eight patients had grade 3 or 4 infections. Two of them died of sepsis and 1 succumbed to uncontrolled pneumonia. The objective response rate was inferior to other series. Possible explanation included longer delay before initiation of definitive treatment, larger tumor burdens, higher severe hematologic toxicity and lower dosage of bleomycin. The results suggested metastatic and/or recurrent nasopharyngeal carcinoma is chemosensitive, however, for patients with large tumor burdens, more intensive chemotherapy regimens with support of hematopoietic growth factors may be required to achieve a better control.
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PMID:Chemotherapy with cisplatin and continuous infusion of 5-fluorouracil and bleomycin for recurrent and metastatic nasopharyngeal carcinoma in Taiwan. 768 18

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.
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PMID:[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. 782 85

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

A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m2, 5-fluorouracil 375 mg/m2, and L-leucovorin 100 mg/m2 on day 1, weekly. Patient characteristics were: median age 53 years (range 36-65); estrogen receptor (ER) status was known in 26 patients and of these 15 (57.7%) patients were ER-positive and 11 (42.3%) ER-negative. Of the 43 patients, 25 (58.1%) and 18 (41.9%) patients had received prior adjuvant chemotherapy and prior adjuvant endocrine treatment, respectively. MFL was administered to 22 (51.1%) patients as first line chemotherapy for advanced disease, while 21 (48.9%) patients had received 1 to 2 cytotoxic regimens for metastatic disease. The dominant sites of metastases were: soft tissue in 11 (25.5%) patients, bone in 8 (18.6%) patients and viscera in 24 (55.9%). All patients were assessable for toxicity: only 8 patients experienced WHO grade 3 leukopenia. Thrombocytopenia, diarrhea, stomatitis, and nausea/vomiting were negligible. Anemia and alopecia were not observed. Thirty-nine patients were assessable for response: overall response rate was 28.2% (complete response 7.7% and partial response 20.5%). Median duration of response was 12 months (range 6-34). Patients with no prior anthracyclines had a 42.1% response rate compared to 15% in patients who had received anthracyclines. Median overall survival of the 43 patients was 6 months (range 1-34). Weekly MFL is a well-tolerated and a moderately effective regimen for the treatment of metastatic breast cancer.
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PMID:Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer. 794 11

This study was to define the efficacy of ifosfamide, mesna, carboplatin, and etoposide (ICE) in patients with metastatic non-small cell lung cancer (NSCLC). From September 1990 to October 1991, 33 patients were treated with ifosfamide/mesna 1.25 g/m2/day and etoposide 80 mg/m2/day intravenously from days 1 to 3, and carboplatin 300 mg/m2 on day 1 every 4 weeks. There were 20 male patients and 13 females. The median age was 65 (range: 38-79). Seventeen patients had a performance status (PS) of 0 or 1, and 16 had a PS of 2 or 3. All had measurable diseases. Nine had initial treatment for localized disease with concurrent radiation, 5-fluorouracil, and interferon-alpha 2b and four had radiation only. None had received chemotherapy for metastatic disease. There were nine partial responses (PR) (27.3%, 9/33) with a median response duration of 8 months (range: 2-16 months). Five patients had stable diseases (SD), which lasted for 3, 6+, 7+, 10+, or 13.4 months. The median survival was 8 months for PR and SD and 4 months for the entire group. Patients with PS of 2 or 3 were less likely to respond (18.8% vs 35.3%) and had a shorter median survival (2.7 months vs 6 months) than patients with better PS. Dose-limiting toxicity was myelosuppression. Seventeen (51.5%, 17/33) patients developed grade III-IV leukopenia with four septic episodes and three septic deaths. Grade III or IV thrombocytopenia was seen in five patients. Patients with prior radiation were significantly more prone to develop leukopenia (P < .005). Gastrointestinal toxicity was mostly mild. No neurologic or genitourinary toxicity was observed. In conclusion, ICE is active in patients with advanced NSCLC and good PS. Besides myelosuppression, it is well tolerated. Further study is indicated to evaluate if granulocyte-colony stimulating factor can reduce myelosuppression from ICE in good PS patients.
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PMID:Phase II study of ifosfamide, carboplatin, and etoposide in patients with advanced non-small cell lung cancer. 797 71

In patients with locally advanced cervical cancer, most of the treatment failures occur within the pelvis. In an attempt to improve local control, 40 patients with bulky tumors (stage IB > 5 cm, stage IIB with distal parametrial invasion, and stage III-IVA) were treated between 1988 and 1992 with concurrent chemoradiation (CCR). The whole pelvis received a midplane dose of 45 Gy over 33 days. Daily radiation dose was 1.8 Gy, with twice-daily fractionation in the last 20 patients. Chemotherapy was administered on the 1st and 21st days of radiation therapy (RT) consisting of cisplatin (60 mg/m2), followed by 5-fluorouracil (600 mg/m2/day continuous i.v. infusion) over 96 hr (and decreased to 40 and 400 mg/m2, respectively, in the last 23 patients). CCR was first followed by a single intracavitary application and then by a parametrial boost in stage IIB-III patients and in stage IVA patients with disease reaching the pelvis side wall. Then surgery (colpohysterectomy with lymphadenectomy or pelvic exenteration) was performed in 35 patients. Median follow-up time was 2.6 years (0.6-5.6 years). Acute toxicity (WHO grade 3-4 diarrhea) in 13 patients led to 6 RT interruptions and 4 incomplete RTs. One patient died of a septic episode without leukopenia after completion of CCR. Five postexenteration complications required a second surgical procedure, of which one patient died with tumor and small bowel fistula. One patient developed small bowel late complication and another patient developed urinary late complications. No postoperative or late complications were observed in patients treated with twice-daily fractionation. Pelvic control was achieved in 32 of 40 patients (81 and 74% in stage IB-IIB and stage III-IVA, respectively). Sites of failure were the pelvis (6 cases), metastases (7 cases), and both (2 cases). Two-year survival and DFS rates were 61 and 66%, respectively, in stage IB-IIB and 77 and 65% in stage III-IVA. High SCC-TA4 values significantly worsened DFS rates. In patients with stage III-IVA tumors, additional surgery could be an important component of this treatment strategy and may be compatible with CCR using twice-daily fractionation radiotherapy. However, these results must be confirmed by a large-scale prospective study.
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PMID:Concomitant chemoradiation prior to surgery in the treatment of advanced cervical carcinoma. 802 Aug 42

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.
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PMID:Chronic oral etoposide in advanced breast cancer. 813 64

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.
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PMID:[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. 821 Feb 51

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

The clinical application of interleukin-2 (IL-2) for the treatment of certain human malignancies has shown promise. However, the use of IL-2 in immunotherapeutic protocols has been limited due to its associated toxicities. The administration of therapeutic doses of IL-2 results in a vascular leak syndrome with associated multiple system organ edema, hypotension, and respiratory, renal, and hepatic dysfunction. Previous studies suggest that the mechanism of these toxicities involves the activation of both immune effector cells and the microvascular endothelium with resultant leukocyte-vessel wall interaction, endothelial cell injury, and subsequent invasion of normal tissues by activated leukocytes. Recently it has been demonstrated that interleukin-8 (IL-8) will inhibit leukocyte adherence to an activated endothelium. Thus, we hypothesized that IL-8 would ameliorate IL-2-evoked detrimental effects. We also investigated the influence of IL-8 on IL-2-induced antitumor efficacy. Four groups of nontumored, female, C57BL/6 mice and four groups of C57BL/6 mice with pulmonary metastases from a 3-methylcholanthrene-induced fibrosarcoma (MCA-105) were treated every 6 hr for 4 days by intraperitoneal injections of IL-2 alone, IL-2 and IL-8, IL-8 alone, or an equal volume of saline which served as our control. Upon completion of therapy, we found that IL-8 suppressed many of the IL-2-induced effects including multiple organ edema, hepatic dysfunction, leukopenia, and lymphocytic infiltration of normal organs. When the number of pulmonary metastases were counted 20 days after the cessation of therapy. IL-8 was also found to significantly ablate the IL-2-elicited antitumor efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-8 suppresses the toxicity and antitumor effect of interleukin-2. 827 74


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