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)

Multiple systemic therapies have been used to treat patients with endometrial cancer. Although progestins have been the standard initial treatment for metastatic disease for the past 30 years, they are effective in only 20% of patients, and several large randomized trials have failed to demonstrate any benefit in the adjuvant setting. Alternative agents such as tamoxifen have shown modest activity. Few studies have investigated combinations of hormonally active drugs. Doxorubicin and cisplatin are the most active cytotoxic agents; a current randomized study is comparing the combination of these drugs with single-agent doxorubicin. Maximizing the effectiveness of established drugs, possibly with hematopoietic growth factors, and identifying alternative hormonal and cytotoxic agents with a sound scientific rationale will hopefully increase the effective treatment options for these patients.
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PMID:Systemic treatment of advanced and recurrent endometrial carcinoma: current status and future directions. 203 21

Thirty four patients treated with mastectomy and axillary node dissection for potentially curable breast cancer received a seven month combined adjuvant chemotherapy and radiation therapy program. These patients were considered to be at high risk for recurrence because they had either three or more positive axillary lymph nodes or their primary tumor was greater than 5 cm in diameter. The chemotherapy given at 3-week intervals consisted of cyclophosphamide, 600 mg/m2, Adriamycin 40 mg/m2, and methotrexate 40 mg/m2 during cycles 1 through 3 and 7 through 9. Radiation therapy was administered during cycles 4 through 6 with concomitant administration of 5-fluorouracil 600 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 7 days. Median follow up time from initiation of study is 60 months (range 36-93). Seventeen of 34 patients (50%) remain free of recurrent breast cancer. Distant metastases and local-regional recurrence have occurred in 16 (47%) and 4 (12%) patients, respectively. Significant myelosuppression and infections requiring hospitalization were seen in 4 patients, with 1 treatment-related death. Adriamycin-containing chemotherapy and post-operative radiotherapy can thus be combined in an adjuvant treatment program with acceptable toxicity.
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PMID:Concomitant adjuvant chemotherapy and radiotherapy for high risk breast cancer patients. 203 39

A total of 59 eligible patients with localized Ewing's sarcoma of the pelvic and sacral bones were entered into a multimodal Intergroup Ewing's Sarcoma Study (IESS-II) (1978 to 1982) and compared with a historical control series of 68 patients entered into an earlier multimodal Intergroup Ewing's Sarcoma Study (IESS-I) (1973 to 1978). High-dose intermittent multiagent chemotherapy (vincristine, cyclophosphamide, Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and dactinomycin) was given to all patients for 6 weeks before and for 70 weeks following local therapy. All patients who had a tumor biopsy or incomplete resection performed received a dose of 55 Gy to the tumor bed. With a median follow-up time of 5.5 years, two of 59 patients (3%) had a local recurrence, five patients (8%) had a local recurrence and metastases, and 17 patients (29%) developed metastases only. There was significant statistical evidence of an advantage in relapse-free survival (RFS) and survival (S) for patients on IESS-II versus IESS-I, P = .006 and P = .002, respectively. At 5 years, the comparison between IESS-II versus IESS-I was 55% versus 23% for RFS and 63% versus 35% for S.
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PMID:Multimodal therapy for the management of localized Ewing's sarcoma of pelvic and sacral bones: a report from the second intergroup study. 204 57

Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi-toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects.
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PMID:Free and liposomal doxorubicin treatment of intraperitoneal colon 26 tumor: therapeutic and pharmacologic studies. 209 39

Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory. Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years. The overall outcome was significantly better on trt 1 than on trt 2. At 5 years, the estimated percentages of patients who were disease-free, relapse-free, and surviving were 68%, 73%, and 77% for trt 1 and 48%, 56%, and 63% for trt 2 (P = .02, .03, and .05, respectively). The major reason for treatment failure for both treatment groups was the development of metastatic disease. The lung was the most common site of metastases followed by bone sites. The combined incidence of severe or worse toxicity (67%) was comparable between the treatments; however, severe or worse cardiovascular toxicity was significantly greater on trt 1. Tne only treatment-associated deaths (N = 3) were on trt 1 and were cardiac-related.
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PMID:Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II. 201 32

Two hundred fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (M), and 5-fluorouracil (F) (VTMF), with or without Adriamycin (A) (doxorubicin; Adria Laboratories, Columbus, OH), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients (130 postmenopausal and 65 premenopausal) and was omitted in 55 patients (31 postmenopausal and 24 premenopausal). There were 19 Stage I, 86 Stage IIA, 51 Stage IIB, 36 Stage IIIA, and 58 Stage IIIB patients. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5-year disease-free survival (DFS) rates were 100% for Stage I, 82% for Stage IIA, 61% for Stage IIB, 46% for Stage IIIA, and 52% for Stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases. The actuarial rate of locoregional recurrence was 13% for T2, 18% for T3, and 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results were excellent or good for most patients. The 5-year overall survival (OS) rates were 95% for Stage I, 94% for Stage IIA, 80% for Stage IIB, 60% for Stage IIIA, and 58% for Stage IIIB. Most patients with breast cancer should be given the option of breast-preserving treatment.
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PMID:Results of neoadjuvant chemotherapy and radiation therapy in the breast-conserving treatment of 250 patients with all stages of infiltrative breast cancer. 211 76

Doxorubicin (DXR) and ME2303, a new fluorine-containing (C'-2) anthracycline derivative, were studied for their tissue distributions--particularly in the plasma, liver and bone marrow--following administration at the maximum tolerated doses to normal mice and mice bearing hepatic metastases of Lewis lung carcinoma. ME2303 was rapidly metabolized and disappeared rapidly from the plasma, liver and bone marrow. Its metabolites--the product of esterolysis (M1) and its reduced derivative at the C-14 position (M2)--remained for a long period except in bone marrow. On the other hand DXR remained in the analyzed tissues for a long period; an especially large amount of DXR was found in the bone marrow even at 24 h after administration of the drug while, in the case of ME2303, by this time even its metabolites had disappeared. The concentrations of M1 and DXR in the liver at 2 h were about 50- and 300-fold higher than their plasma concentrations. The tissue distributions in the normal mice and hepatic-metastases-bearing mice showed no significant differences. Regarding the antitumor effects of ME2303, M1, M2 and DXR in the hepatic-metastases-bearing mice, ME2303 was the most effective compound, and M1 was also active; DXR showed only a marginal effect, and M2 showed no effect.
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PMID:Therapeutic activity and tissue distribution of ME2303, a new anthracycline containing fluorine, and its metabolites in mice bearing hepatic metastases of Lewis lung carcinoma. 213 Oct 42

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.
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PMID:Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group. 213 77

Patients suffering from metastatic breast cancer and recurrent fever were investigated for viral reactivation or new viral infection as a possible cause of these febrile episodes. Three groups of patients were included in the study: (a) patients under adjuvant chemotherapy with cyclophosphamide, methotrexate and fluoruracil, (b) patients with stable metastatic disease treated with cyclophosphamide, fluoruracil and Adriamycin or mitoxantrone and (c) patients with progressive metastatic disease who also received the latter treatment. During the time of observation, patients under adjuvant chemotherapy did not present with fever or asymptomatic viral reactivation or bacterial infections at all. Out of 7 patients with stable disease, 2 had bacterial infections that coincided with the leukocyte nadir, and 1 presented with asymptomatic reactivation of cytomegalovirus. In contrast, fever in 9 of 11 patients with progressive disease was associated with a reactivation of herpes simplex virus (HSV) and in 3 of them with a consecutive reactivation of varicella zoster virus (VZV). The increase in complement-fixing anti-HSV or anti-VZV antibodies occurred in close association with a rise of the respective preexisting antibodies of the IgG class. In addition, HSV-infected cells were recovered from the urine of 7 patients with progressive disease further corroborating the serological data. Incidentally, natural killer cell activity, which has been postulated to be connected with the defense against viral infections, was found to be significantly lower in the group of patients with progressive disease, as compared to the group of patients under adjuvant chemotherapy (P less than 0.05) or to the group of patients with stable disease (P less than 0.05). We conclude that unexplained fever in patients with progressive metastatic breast cancer may result from viral reactivation.
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PMID:Viral reactivation as a cause of unexplained fever in patients with progressive metastatic breast cancer. 215 48

Data from patients with pulmonary metastases (PM) from Wilms' tumor at diagnosis (stage IV) were collected from six European centers. All patients were pretreated with a chemotherapy (CT) regimen consisting of vincristine (VCR), dactinomycin (AD), and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). After nephrectomy, local therapy for residual pulmonary disease was considered to avoid whole-lung irradiation. Only four of 36 patients still had multiple inoperable metastases after preoperative CT. Thirty patients survived. Four of them were irradiated. Of the six patients who died, four died of PM, one died of abdominal recurrence, and one of therapy-related disease. Disease-free survival and actuarial survival rates are 83% with a mean follow-up of 4 years postnephrectomy.
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PMID:Wilm's tumor with pulmonary metastases at diagnosis: the significance of primary chemotherapy. International Society of Pediatric Oncology Nephroblastoma Trial and Study Committee. 216 11


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