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)

Seventeen patients with advanced renal pelvic and ureteral carcinoma receiving M-VAC chemotherapy were evaluated. There were 10 men and 7 women ranging in age from forty-two to seventy-eight years with a mean of sixty-six years. The primary sites of carcinoma were renal pelvis in 4 patients, ureter in 12, renal pelvis and ureter in 1. Fifteen patients had transitional cell carcinoma, one patient had transitional cell carcinoma mixed with squamous cell carcinoma and the histology of one patient was not identified. The median number of treatment cycles was 2.6, ranging from 1 to 6. Significant remissions following the treatment were observed in 5 of 8 primary lesions, 6 of 11 lymph nodes, 2 of 3 lung lesions and 2 of 5 bone lesions, respectively. However, the responses were not seen in 4 liver lesions. Two patients achieved a complete response (CR), 7 had a partial response (PR), 6 had stabilization of their disease, 2 had progressed, and the overall response rate was 52.9%. Two CR patients remain free of disease. Relapse or recurrence was seen in 4 of the 7 patients who achieved PR, and the median duration of response was 6.4 months. While the myelosuppression with this regimen was tolerable, the decreases of white blood cell and platelets count were significant in patients who had undergone prior irradiation. These results indicate that the M-VAC regimen is effective in patients with advanced upper urothelial malignancy. Further, a short response and a poor effectiveness in the metastases of liver and bone remain to be overcome.
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PMID:[M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy in advanced renal pelvic and ureteral carcinoma]. 267 46

Sixteen patients with lymph nodes metastases and/or locally advanced bladder carcinoma were treated with a combination chemotherapy regimen consisting of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC) from November 1986 through September 1988. There were 14 men and 2 women. The median age was 61.9 years, with a range from 43 to 81 years. Complete response (CR) was observed in 6 of 16 patients (38%), partial response (PR) was confirmed in 5 of 16 patients (31%), and overall response rate was 69%. Median duration of response was 10.3 and 5.2 months in CR and PR patients, respectively. The myelosuppression with this regimen was tolerable. This study demonstrates that the M-VAC regimen is effective in the invasive bladder carcinoma with or without lymph nodes metastases. However, the duration of response is relatively short, and the true long-term benefits of this regimen remain to be determined.
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PMID:[M-VAC chemotherapy for patients with lymph node metastases and/or locally advanced bladder carcinoma]. 268 48

Both cisplatin and leucovorin may increase the activity of 5-fluorouracil (5-FU) by increasing the intracellular concentration of reduced folates. Therefore, a Phase I study was conducted in patients with recurrent or metastatic head and neck cancer in which high doses of oral leucovorin were added to the combination of cisplatin and 5-FU. Patients received intravenous cisplatin 100 mg/m2 on day 1, followed by a continuous intravenous infusion of 5-FU at 600 mg/m2/day for 5 days. Leucovorin 50 mg/m2 orally was administered from the start of the cisplatin infusion and then every 6 hours throughout the 5-FU infusion. The dose of 5-FU was increased to 800 mg/m2/day and 1 g/m2/day according to observed toxicity. In a second phase of the study, the dose of leucovorin was increased to 50 mg/m2 orally every 4 hours. Twenty-five patients were registered: 23 had recurrent head and neck cancer after extensive treatment; two had newly diagnosed metastatic disease. The maximum tolerated dose of 5-FU was 800 mg/m2/day with leucovorin administered every 6 hours. Toxicities at that level included mild-to-moderate myelosuppression. Mucositis in the previously irradiated field prevented the further increase of the 5-FU dose to 1 g/m2/day. Identical toxicities were observed when administering 5-FU at 800 mg/m2/day with 50 mg/m2 of leucovorin every 4 hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who had previously received cisplatin and 5-FU as induction chemotherapy). Eight patients did not respond. The median survival for all 25 patients was 6.5 months. It was concluded that the combination of cisplatin, 5-FU, and leucovorin is active in the treatment of recurrent head and neck cancer. The maximum tolerated dose of 5-FU in previously treated patients is 800 mg/m2/day, with mucositis being the dose-limiting toxicity. Further investigation of this regimen as neoadjuvant chemotherapy in previously untreated patients with locally advanced head and neck cancer is in progress.
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PMID:Cisplatin, 5-fluorouracil, and high-dose oral leucovorin for advanced head and neck cancer. 278 81

Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.
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PMID:Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy. 280 87

Concurrent administration of degradable starch microspheres and cytostatic agents into the hepatic artery results in decreased systemic exposure and increased hepatic exposure to drug compared to intra-arterial administration of drug alone. Degradable starch microspheres 210 mg/m2 mixed with floxuridine 500 mg/m2, doxorubicin 40 gm/m2, and mitomycin 10 mg/m2 were administered through hepatic artery catheters to eleven patients with primary or metastatic cancer of the liver. Toxicity was acceptable and consisted of severe myelosuppression (5%), duodenal/gastric ulceration (9%), mild to moderate nausea and vomiting (17%) and alopecia (86%). There were no responses among the eleven patients; 7 of 7 patients with colo-rectal carcinoma had stable disease while on study. Minimal activity was observed in 7 patients with colo-rectal carcinoma. The use of degradable starch microspheres offers a new approach to the regional treatment of cancer and warrants further study.
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PMID:Pilot study of intra-arterial floxuridine, mitomycin and doxorubicin in combination with degradable starch microspheres to treat primary and metastatic tumors of the liver. 293 38

Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and alkaline phosphatase, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression. Granulocytopenia or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.
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PMID:Relationship between myelosuppression and chemotherapeutic response in small cell bronchogenic carcinoma. 298 16

Although increased efficacy has been described with a five-day schedule of high-dose cisplatin (CDDP) in hypertonic saline, severe myelosuppression and cumulative neurotoxicity have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in non-small-cell lung cancer (NSCLC), 17 patients with metastatic disease were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per patient and a median total cumulative dose of 600 mg/m2. Nine of 17 patients received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and peripheral neuropathy were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe peripheral neuropathy developed in only one patient (6%). The overall response rate was 47% (eight of 17 patients). Plasma platinum pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate platinum occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced toxicity of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in NSCLC remains to be defined. In view of reduced myelosuppression and neurotoxicity, further trials with this modified schedule are indicated.
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PMID:High-dose cisplatin in hypertonic saline: reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in non-small-cell lung cancer. 302 57

High-dose etoposide (1.0-1.5 g/m2) was given to 17 small cell lung cancer (SCLC) patients with metastases in the central nervous system. In 4 out of 9 evaluable patients with brain metastases and 4 out of 5 patients with meningeal carcinomatosis a response was seen. In all patients severe myelosuppression was observed. Three patients died of septicemia during the aplastic phase. Despite severe toxicity high-dose etoposide is potentially useful for CNS metastases of SCLC.
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PMID:High-dose etoposide for central nervous system metastases of small cell lung cancer. Preliminary results. 303 52

The clinical experience is reviewed in 597 Norwegian testicular cancer patients (age range: 15-45 years) treated from 1979 to 1986. During this period, computer tomography, determination of serum AFP/HCG, and cisplatin-based chemotherapy represented the modern diagnostic and therapeutic modalities. Before orchiectomy 67% of the patients had elevated AFP/HCG. An abnormal postorchiectomy serum tumour marker decrease and the presence of small vessel infiltration in the histological sections of the primary tumour significantly predicted microscopic retroperitoneal metastases in patients with clinical stage I (CSI) nonseminoma. One-third of these patients had a pathological stage II (PSII). After radiotherapy 99% of 90 seminoma patients (CSI/IIa) survived for 5 years. After cisplatin-based chemotherapy (+radiotherapy/surgery) the 5-year survival rate in 25 patients with advanced seminoma was 81%. The survival rate in 148 nonseminoma patients PSI/IIa was 100% and 87% in 94 patients with advanced nonseminoma (greater than or equal to CSIIb). Nausea, general exhaustion, myelosuppression, peripheral neuropathy, and Raynaud-like phenomena were the main acute treatment-related side effects. Slight gastrointestinal problems, slight peripheral neuropathy, Raynaud-like phenomena, and fertility disturbances were frequent late side effects. The sexual life in testicular cancer patients did not seem to be significantly impaired as compared to the normal population. Most of the patients reported no or only slight emotional problems during and after treatment. The need of thorough information at the time of diagnosis was stressed by most of them. Secondary cancer was diagnosed in 27 of 795 patients (1970-1982) (Testicular: 15; pulmonary: 4; sarcoma: 2; others: 6). Testicular cancer is today a curable malignancy. Future clinical research has to concentrate on the identification of high-risk and low-risk patients, the avoidance of overtreatment, and the reduction of toxicity (especially of long-term side effects).
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PMID:Testicular cancer in young Norwegians. 304

Twenty-five women with advanced breast cancer were treated in a phase II trial of iproplatin 275 mg/m2 administered intravenously every 4 weeks. All patients had measurable or evaluable indicator lesions, and had undergone treatment with no more than one previous chemotherapy regimen, including adjuvant chemotherapy. Two of the twenty-four evaluable patients (8%) experienced major therapeutic responses. One patient had a complete regression of pulmonary nodules lasting 18+ months; another had a partial regression of metastatic disease in the liver (4 months). The inevaluable patient was ineligible for the study because of previous radiation to the indicator lesions on her chest wall; nonetheless, she experienced a 10 month partial regression of those nodules. Myelosuppression was generally dose limiting; thrombocytopenia was more profound, but leukopenia was more prolonged. Nausea, vomiting, diarrhea, and general malaise were prominent toxicities, and led to discontinuation of therapy in 4 patients. Iproplatin has limited activity in previously treated women with advanced breast cancer.
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PMID:Clinical trial of iproplatin (cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV, CHIP) in patients with advanced breast cancer. 304 33


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