Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.
 ...
PMID:Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma. 167 Nov 4

The use of chemotherapy in patients with head and neck cancer is increasing. In patients with recurrent head and neck cancer, a large number of chemotherapeutic drugs have shown antitumor activity. These drugs are discussed, and factors which influence response rate and survival are examined. New agents and treatment, including specific agents for combination chemotherapy, are presented. There has been a search for new treatments or procedures in patients with previously untreated and locally advanced cancer of the head and neck. The results, including studies of combined modality therapy and chemotherapy after surgery, are discussed. Chemotherapy in tumor of the salivary glands is briefly discussed, followed by an examination of intra-arterial therapy.
Cancer Metastasis Rev 1987
PMID:Chemotherapeutic management of head and neck cancer. 331 71

The survival of patients with locally advanced cancer of the cervix (stage IIB, IIIB, and IVA) treated with conventional intracavitary radium remains unsatisfactory. Over 50% of these patients are local failures and die with uncontrolled tumor in the pelvis. In 1978, we began performing transperineal interstitial implants to the parametria in patients with advanced disease. One hundred six evaluable patients (34 IIB, 67 IIIB, and five IVA) received one (99) or two interstitial implants (7) following 40-50 Gy of external supervoltage external irradiation. In addition, seven patients underwent exploratory staging laparotomies concurrently with the first implant procedure. Mean follow-up is 23 months and range is 12-60 months. Control of the pelvic tumor has been documented in 85%, 75%, and 40% of stage IIB, IIIB and IVA patients, respectively. Seven patients developed distant metastases and three died of intercurrent disease with no evidence of pelvic relapse. Nineteen patients (18%) developed radiation-related complications: proctitis or cystitis (six), rectal stenosis (six), ulceration and necrosis of the vaginal wall (one), and recto- or vesicovaginal fistula (six). It is noteworthy that 7/11 patients (64%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for an intrauterine tandem developed severe complications. We conclude that transperineal interstitial irradiation is both safe and an effective modality in the treatment of advanced cancer of the cervix.
 ...
PMID:Treatment of locally advanced cancer of the cervix with transperineal interstitial irradiation. Report on 106 cases. 663 76

The treatment of prostatic adenocarcinoma is the subject of debate and controversy at all stages of the disease. At the initial "subclinical" stage, discovered in transurethral resection or prostatectomy specimens, the conservative approach generally adopted should sometimes be replaced by curative treatment in young patients or in the case of high grade cancers. The localised, intraprostatic stage is amenable to curative treatment. However, radical prostatectomy may not be indicated in the presence of lymph node metastases and the discovery of positive margins on histological examination of the resection specimen raises the question of the necessity and the chronology of complementary treatments. At the stage of locally advanced cancer, all therapeutic modalities have been proposed in various combinations. The most controversial question concerns neoadjuvant endocrine therapy prior to radical prostatectomy. Metastatic disease is treated by endocrine therapy. However, the necessity of complete androgen blockade chemotherapy has still not been demonstrated. No effective therapeutic solution has yet been found for "endocrine escape", but a number of palliative measures should improve the quality of the patient's limited survival.
 ...
PMID:[Current questions and controversies on the treatment of prostate cancer]. 814 51

Gastric adenocarcinomas, even in the absence of distant metastases, have a poor prognosis which is particularly dismal when tumors are located in the cardia, in the event of locoregional lymph node involvement and/or bulky tumors. Postoperative adjuvant chemotherapy has never clearly demonstrated its efficacy on survival. Besides ongoing trials using new and more active regimens, preoperative chemotherapy has been used for unresectable cancer due to loco-regional extension and when locally advanced cancer is potentially resectable but with poor prognosis such as bulkiness, when tumors are located in the cardia and when there is tumor in the coeliac area at CAT-scan with suspected metastatic lymph nodes. In case of unresectable tumor at initial surgery five publications have reported the ability of chemotherapy to reduce the tumor volume and to allow subsequent resection of the gastric tumor in 40% to 60% of the cases. In these cases there is a clear survival advantage as the median survival reported in 2 of these studies was 12 and 18 months compared to the 4 to 6 months median survival reported in historical studies in case of unresectable cancer [17, 18]. In case of locally advanced gastric tumors some Japanese case reports have demonstrated the ability of preoperative chemotherapy to concentrate in the tumor tissue and to downstage the tumors. Four North American and European studies have demonstrated that preoperative chemotherapy is feasible, and will probably increase the resection rate. J. Ajani has reported 2 studies in which tolerance was acceptable: a major response (R) observed in 24% and 31%, the resectability rates were 72% and 77% and the median survival 15 and 16 months, respectively. Our experience is based on 30 patients treated with a combination of continuous i.v. 5-FU and CDDP. Fifteen had a tumor of the cardia, 15/30 had enlarged lymph nodes and 7/30 a linitis plastica (diffuse type). After a mean number of 3 cycles, 27/30 patients were evaluable for response. One patient achieved a CR and 14 a PR (OR rate 56%, 95% CI: 38% to 74%) but only one of those with linitis plastica responded. Twenty-eight patients underwent surgery and 23 had a macroscopically complete resection (82%). Resectability rate was higher after OR (13/15) than in nonresponding patients (4/12). Toxicity was acceptable, however grade 4 leucopenia in 5 patients and one toxicity-related death were observed. There was no increase in postoperative complications. Nine patients received postoperative chemotherapy and 3 patients with positive margins received postoperative external radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Preoperative chemotherapy of locally advanced gastric cancer. 820 31

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)
 ...
PMID:[Chemofiltration for locally advanced cancer]. 834

In this phase II trial 31 patients with advanced gastric cancer (21 with metastatic cancer and 10 with locally advanced cancer) were treated with a continuous 24-hour infusion of 5-fluorouracil (5-FU) 330 mg/m2/day plus low-dose cisplatin (CDDP) 6 mg/m2/day by bolus infusion on days 1-5. The regimen with a combination of 5-FU and low-dose CDDP (FLDP) was repeated weekly for two to four courses according to response and tolerance. In 24 (77%) of the 31 patients, four courses of this regimen were administered. The overall response rate was in 14/31 (45%) patients with measurable disease, including one complete response and 13 partial responses. An especially high response rate of 60% was seen in 10 patients with liver metastasis. Median survival time was 11 months (range 6-27+) in the 10 cases of locally advanced cancer and 11 months (range 6-24+) in the 21 cases of metastatic cancer. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of World Health Organization (WHO) grade 3 or 4 occurred in 4/31 (13%) and 4/31 (13%) of patients, respectively. Renal dysfunction, which is a major toxicity associated with CDDP, was not observed without hydration. The patients were able to eat during therapy and preserved a good quality of life. A randomized trial including the FLDP regimen is needed to compare it with other active regimens, particularly the use of high-dose CDDP.
 ...
PMID:Feasibility study on protracted infusional 5-fluorouracil and consecutive low-dose cisplatin for advanced gastric cancer. 857 Jan 35

Experimental tumors contain a significant fraction of microregions that are chronically or transiently hypoxic. Experimental evidence showing that hypoxia (and subsequent reoxygenation) may have a profound impact on malignant progression and on responsiveness to therapy is growing. The clinical relevance of tumor oxygenation in human solid malignancies is under investigation. We have developed and validated a clinically applicable method for measurement of tumor oxygenation in locally advanced cancer of the uterine cervix using a computerized polarographic electrode system. Applying this procedure in patients with cervical cancers </= 3 cm in diameter, who gave informed consent, we have been studying the clinical relevance of tumor oxygenation prospectively since 1989. As of June 1995, 103 patients with advanced cancers of the uterine cervix [Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stages Ib, bulky (n = 13), IIa and IIb (n = 51), IIIa and IIIb (n = 34), and IVa and IVb (n = 5)] had entered the study. Fifty % of the patients had carcinomas with median pO2 readings <10 mm Hg, referred to as hypoxic tumors. Tumor oxygenation was found to be independent of various patient demographics and also of pretreatment tumor characteristics, such as clinical tumor stage and size, histological type, and differentiation. However, histopathological examination of the surgical specimens following radical tumor resection in 47 patients showed that low-pO2 tumors exhibited larger tumor extensions and more frequent (occult) parametrial spread, as well as lymph-vascular space involvement, compared to well-oxygenated tumors of similar clinical stage and size. Forty-two patients completing primary radiation therapy and 47 patients who underwent radical surgery were analyzed for treatment outcome after a median observation period of 28 months (range, 3-76 months). Patients with hypoxic tumors had significantly worse disease-free and overall survival probabilities compared to patients with nonhypoxic tumors. Cox regression analysis identified tumor oxygenation and FIGO stage as the most important independent prognostic factors. The poorer outcome of the patients with hypoxic tumors was mainly due to locoregional failures with and without distant metastases, irrespective of whether surgery or radiation was applied as primary treatment. Tumor oxygenation as measured with a standardized polarographic method proved to be a powerful new pretherapeutic prognostic parameter providing important information on malignant progression in terms of extracervical tumor spread and radioresistance in advanced cervical cancers.
 ...
PMID:Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. 881 49

This report reviews the long-term follow-up of a prospective Phase II evaluation of intermittent androgen suppression in the treatment of prostate cancer. A total of 87 patients have been entered in this protocol. At the time of this report, 50 men have been followed for a minimum of 3 years. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum PSA nadir was observed. Medication was then withheld until the serum PSA increased to mean values between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of PSA became androgen independent. The total time in the study ranges from 40 to 126 months, with a mean of 65.5 months. The off-treatment period in the first cycle for the men with long-term follow-up was associated with an improvement in the sense of well-being and recovery of libido and potency in men who reported normal or near-normal sexual function before the start of therapy. The average time off therapy (percentage time off therapy) for cycles 1, 2, 3, and 4 was 15 months (54%), 10 months (48%), 8 months (45%), and 7 months (40%), respectively. The study group included 9 patients treated because of a rising PSA concentration after radiation therapy for locally advanced cancer. These patients have been off therapy for an average of 22 and 13 months in treatment cycles 1 and 2, respectively. Six patients with rising PSA values after radical prostatectomy and with follow-up exceeding 36 months have been off therapy for an average of 19 and 11 months in treatment cycles 1 and 2, respectively. Of the 87 patients, 23 have had their disease progress to androgen independence at a median of 32 months of treatment, and 13 have died cancer-specific deaths at a median of 48 months. Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy, with reduced toxicity and costs. Phase II trials suggest that there is not a negative impact on patient outcome. Randomized protocols are currently in progress to determine whether survival is affected in a beneficial or adverse way by such treatment in men with locally recurrent or metastatic cancer.
 ...
PMID:Clinical Experience with Intermittent Androgen Suppression in Prostate Cancer: Minimum of 3 Years' Follow-Up. 1085 35

Local treatment with surgery and radiotherapy gives unsatisfactory results in patients with locally advanced cancer. In many cases distant metastases appear shortly after the removal of the primary tumor. Selecting breast cancer as a model for locally advanced disease, we are extrapolating our findings to other solid tumors. Neoadjuvant chemotherapy has improved survival of these patients by downstaging the primary tumors allowing local treatment and early elimination of distant micrometastases. We recently reported in this journal on a study of 42 patients with locally advanced breast cancer (LABC) who received prolonged neoadjuvant chemotherapy of doxorubicin, cyclophosphamide, and GM-CSF prior to surgery and postoperative radiotherapy. These results were promising and prompted us to initiate an international randomized phase III study in which either six neoadjuvant cycles or three neoadjuvant cycles plus three adjuvant cycles are being compared. In LABC patients treated with six neoadjuvant chemoimmunotherapy cycles, we observed a significant rise in the dendritic cell content of the axillary tumor-draining lymph nodes after therapy, associated with an encouraging disease free survival and overall survival. We hypothesize that the prolonged presence of draining lymph nodes in combination with the repeated tumor antigen release, dendritic cell recruitment, and activation may account for the observed increased survival of LABC patients. Based on our findings and the results of preclinical studies, we hypothesize that it is more effective to administer chemotherapy in an extended neoadjuvant regimen, taking advantage of the concurrent biological and immunological processes in the primary tumor and its draining lymph nodes.
 ...
PMID:Biological concepts of prolonged neoadjuvant treatment plus GM-CSF in locally advanced tumors. 1111 Jun 1


1 2 3 4 Next >>