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)

32 patients with advanced non-small cell lung cancer previously untreated by chemotherapy were included in a phase I-II study in order to determine the feasibility of the combination of vinorelbine and cisplatin, each administered at its optimal dose, i.e. 30 mg/m2 weekly and 120 mg/m2 every 4-6 weeks, respectively. There were 27 males and 5 females with a mean age of 55 years and a median performance status of 80%. 13 had locally advanced disease and 19 had distant metastases at the time of inclusion. Our study demonstrated the feasibility of this protocol. Dose intensities could be maximised by adapting vinorelbine doses rather than by postponing treatment in the event of neutropenia. Both response rate (33%) and overall survival of the population (median 11 months) justify further studies.
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PMID:Phase I-II study of vinorelbine (Navelbine) plus cisplatin in advanced non-small cell lung cancer. 132 22

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.
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PMID:Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer. 132 13

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.
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PMID:[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer]. 133 11

Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of the head and neck region. Six of these patients also received mitomycin (DEB/M) when their disease failed to respond after at least three weekly DEB doses. All but three patients had been treated previously with radiotherapy directed to the primary site and regional nodal disease; four had also received chemotherapy with cisplatin or carboplatin. Before treatment with DEB, 19 patients had distant metastases. Of an intended 12 doses per patient, a mean of 8.2 was achieved. Myelosuppression was the major toxicity, with neutropenia in 45% of patients and significant anemia in 26%. The overall response rate to DEB in 27 patients was 59%, increasing to 70% after the addition of mitomycin. There were two complete and 17 partial responses. The median duration of response was 12 weeks and median survival was 6 months, with 20% of patients surviving 1 year. We conclude that the relatively short survival time together with the significant toxicity of the DEB/M regimen does not warrant its routine use in clinical practice. However, this regimen, or one patterned on it, should be evaluated in combination with radiotherapy as the initial treatment for selected patients with previously untreated head and neck cancer.
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PMID:Treatment of recurrent and metastatic head and neck cancer with cisplatin/etoposide/bleomycin. 138 40

Thirty nine patients with metastatic breast cancer, all previously treated with chemotherapy including anthracycline, were given Elliptinium acetate (80 mg/m2/day) and a continuous infusion of Vinblastine (2 mg/m2/day) for 3 consecutive days every 4 weeks. Twenty nine patients had measurable metastatic disease. Nine (31%) achieved a partial response. No complete response was observed. Median duration of response was 6 months. The response rate was dependent on the number of metastatic sites and independent of the number of previous chemotherapy regimes. Side effects were dry mouth (27 patients), vomiting (9), neutropenia (3 patients with grade IV, 2 with grade III), muscle cramps (5) and thrombosis (3). Xerostomia and vomiting contributed to weight loss and fatigue (8 patients). We conclude that Elliptinium-Vinblastine combination has moderate activity as second line treatment in metastatic breast cancer. This combination causes xerostomia and fatigue with moderate myelosuppression.
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PMID:Phase II study of a combination of elliptinium and vinblastine in metastatic breast cancer. 148 4

The combination of cisplatin and cytosine arabinoside has been shown in experimental models to be synergistic. We conducted a pilot study of cytosine arabinoside and cisplatin in unresectable or metastatic cancer of the esophagus in five patients and found significant activity, also on visceral metastasis. Therefore, we decided to examine this combination in the neoadjuvant setting. Since January 1989, eight patients with squamous cell carcinoma esophageal cancer were treated with two cycles of cytosine arabinoside (50 mg/m2) by continuous infusion for 4 days and by cisplatin (100 mg/m2) on the 5th day. Their ages ranged from 54-79 years. One patient had Stage I, three had Stage II, and four had Stage III disease. Responses assessed by endoscopy and computed tomographic (CT) scan prior to surgery were three with partial response, three with minor response, and two with no response. Only six patients were surgically resectable after chemotherapy. Toxicity consisted of grade 3 (one patient) and grade 4 (two patients) neutropenia, grade 3 (three patients) anemia, and grade 3 (two patients) and grade 4 (three patients) thrombocytopenia. All patients had subjective improvement of dysphagia 4 weeks after chemotherapy. Median survival of the whole group was 7.5 months. We concluded that there was no evidence of synergy of these drugs given in this manner in esophageal carcinoma since the response rate was no different from that achieved with cisplatin alone.
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PMID:Neoadjuvant chemotherapy with cytosine arabinoside by continuous infusion and cisplatin for resectable squamous cell carcinoma of the esophagus. 159 82

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).
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PMID:Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B. 163 44

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
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PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.
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PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer. 169 72

To assess the feasibility and effectiveness of combined therapy on locally advanced cervical cancer, we entered 38 patients into a study. The patients were treated with mitomycin-C (10 mg/m2) on Days 1 and 30 and 5-FU (1000 mg/m2) on Days 1 to 4 and Days 30 to 33. In 5 weeks 4500-5000 cGy was given concurrently, followed by radioactive implants. Twenty-six patients had an early-stage disease (IB-IIB) and twelve had a late-stage disease (IIIB-IVA). Eighty-seven percent (33/38) of the patients had a tumor measuring 5 cm or more. The other 5 patients with a tumor size under 5 cm had biopsy-proven positive pelvic nodes; 2 of these 5 patients had a pretherapy hysterectomy. Tumor response, complete (CR) vs partial (PR), was assessed in 36 patients 3 months after completion of therapy. A CR was noted in 80% (29/36) of the patients. The PR status conferred a detrimental effect on the pelvic disease control (PDC), disease-free survival (DFS), and survival (S) while late stage correlated with the development of distant metastases (DM) and a poor DFS. PDC was obtained in 93% (27/29) of the patients who had a CR, as compared to only 43% (3/7) of those with a PR (P = 0.0228). The DFS and S rates were 59 and 77% for patients with a CR and 21 and 19% for those with a PR; respective P values were 0.0340 and 0.0002. Eleven percent (3/26) of the patients with an early stage developed DM, as compared to 50% (6/12) of those with late stage, (P = 0.0016). The DFS rates were 80 and 37% for patients with an early and late stage, respectively (P = 0.0141). Four patients developed transient neutropenia and one had transient thrombocytopenia. The second dose of mitomycin-C was omitted in 4 patients due to persistent neutropenia in 3 and to transfusion-related hepatitis in 1. Two percent (5/21) of the patients who had a staging laparotomy developed wound dehiscence. Three patients developed non-cancer-related small bowel obstruction requiring surgery. We concluded that this combined regimen was well tolerated. Although it was effective in controlling the cancer in the pelvis, this regimen failed to control DM in late-stage patients.
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PMID:Mitomycin-C/5-FU and radiation therapy for locally advanced uterine cervical cancer. 175 91


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