Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum protein-bound carbohydrates, L-fucose, sialic acid, D-galactose, and D-mannose, were measured as potential biologic markers in patients with breast cancer with the use of high-resolution anion exchange separation in combination with a sensitive cerate oxidimetric fluorescence detector system. For 22 randomly selected patients with proved metastatic breast cancer, both L-fucose and sialic acid levels were above the normal range in 21 patients (95%). In contrast, D-mannose was increased in the sera of 9 patients (41%), and D-galactose in 6 (27%). By comparison, the level of carcinoembryonic antigen (CEA) was elevated in 14 patients (64%). The levels for serially determined serum protein-bound carbohydrates paralleled objective changes of response or progression in 5 patients with measurable disease. As might be expected, the degree and pattern of elevation for the individual carbohydrates varied for each patient studied. Combinations of serum protein-bound carbohydrates, particularly L-fucose and sialic acid, and, in addition, CEA, appear to have promise as potential biomarkers for following the course of the disease in patients with metastatic breast cancer.
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PMID:Serum protein-bound carbohydrates for following the course of disease in patients with metastatic breast carcinoma. 27 47

A controlled clinical trial that used high doses of medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer was conducted. Therapy consisted of 2 treatments: regimen A, 500 mg daily with a total dose of 30 g; regimen B, 1000 mg daily with a total dose of 60 g. From June 1975 to September 1976, 101 patients entered into the study and were randomly allocated into the 2 treatment groups. Both treatment groups were comparable in terms of age, menopausal status, free interval, and dominant site of lesions. Selection of patients was done according to the following criteria: histologically proved progressive metastatic carcinoma of the breast, without any treatment for at least 2 months; no prior hormonal manipulation; performance status 50 or more, and life expectancy longer than 3 months; measurable disease. Overall response rates were similar, with no statistically significant difference between the 2 treated groups. Regimen A reached a remission rate of 44%; regimen B had a remission rate of 41%. The mean duration of response was 8 months with regimen A and 9 months with regimen B. Both regimens were well tolerated. Clinical toxicity was mild with both dosages of MPA. The main side effect was gluteus abscess, with a higher incidence in group B. This was probably due to the greater amount of injected drug suspension in the 1000 mg/day regimen. The incidence of thrombophlebitis and vaginal bleeding was negligible.
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PMID:High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. 35 47

Serum fucose-protein ratio was evaluated as a potential biologic marker for patients with metastatic breast cancer. By analysis of the same blood samples, comparisons were made with carcinoembryonic antigen (CEA) and human chorionic gonadotrophin (hCG). For 150 patients with metastatic breast cancer, 85% had a value for serum-fucose protein ratio above the normal range in comparison to 75% for CEA and 40% for hCG. Serum fucose-protein ratio was exclusively increased in 12% of the patients, CEA in 4% and hCG in 2%. Both serum-fucose protein ratio and CEA were elevated in 39% of the patients, and together, either in combination of alone, were increased in 93% of the patients. Raised values for serum fucose-protein ratio as well as for CEA decreased with change in disease status from pretreatment to response for patients with measurable disease parameters and increased correspondingly with overt disease progression. Preliminary data indicate both serum fuxose-protein ratio and CEA frequently become elevated when patients progress from a disease free interval after surgery to recurrence.
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PMID:Biologic markers in breast carcinoma. IV. Serum fucose-protein ratio. Comparisons with carcinoembryonic antigen and human chorionic gonadotrophin. 64 32

A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients each received 480, 800, and 1280 mg/d; 48 patients received 1600 mg/d. Of the 57 patients, 56 patients had had disease progression on prior hormone therapy, chemotherapy, or both. Twenty-seven patients had previously received standard-dose MA (160 mg/d). Among the 37 patients with measurable disease, high-dose megestrol acetate (HDMA) produced 6 (16%) complete responses (CRs) and 6 (16%) partial responses (PRs); 11 patients achieved stable disease (SD). HDMA resulted in improvement or stabilization in 12 of the 20 patients with evaluable, non-measurable disease. There were no responses among the 6 patients with liver metastases. Among the 27 patients who were previously treated with standard-dose MA, including 9 patients with primary treatment failure, HDMA resulted in 1 CR, 3 PRs, and 10 SD. Toxicities, which were mild and reversible, included fluid retention, hypertension, hyperglycemia, and mild congestive heart failure. Two patients had superficial phlebitis. The most profound side effect was weight gain which occurred in 43 patients (75%). This study suggests a dose-response relationship for MA in the treatment of advanced breast cancer. A randomized trial to determine the optimal dose is ongoing.
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PMID:A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer. 175 60

Twelve postmenopausal women with inoperable or metastatic breast cancer were given toremifene at a daily dose of 60 mg. The patients had no prior endocrine or cytotoxic therapy and further inclusion criteria were bidimensionally measurable disease, performance status above 50, expected survival of more than 3 months and estrogen receptor status positive or undetermined. Objective response [complete remission (CR) + partial remission (PR)] was achieved in 6 patients (50%) and stable disease was obtained in 5 patients. No side effects of the treatment were noted.
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PMID:Phase II clinical study of toremifene in patients with metastatic breast cancer. Preliminary communication. 214 42

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.
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PMID:A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. 291 36

WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.
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PMID:Clinical trials of WR-2721 and cis-platinum. 254 Nov 21

The Eastern Cooperative Oncology Group (ECOG) conducted a pilot study of combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil plus aminoglutethimide (250 mg three times daily with hydrocortisone supplementation of 40 mg daily) as primary therapy for estrogen receptor-positive or unknown advanced breast carcinoma to assess whether these agents can be safely combined and to provide a preliminary estimate of response rate. A total of 47 patients, 45 with metastatic breast cancer and two with stage IV disease who were rendered clinically disease free following surgical resection of chest wall recurrence, were treated. Leukopenia and mucositis were the most frequent toxicities requiring dose reduction, but only five patients (10.6%; 95% confidence interval, 1.8-18.4%) experienced life-threatening leukopenia (less than 1000/mm3) at some point during their therapy. Neurologic side effects attributed to aminoglutethimide, predominantly lethargy, were reported in less than one-third of patients, and rarely required dose reduction. One elderly patient developed clinical hypothyroidism during the first 3 months on therapy and experienced a cardiac arrest at home while receiving supplemental thyroid hormones. The overall complete plus partial response rate in 45 patients was 55.5% (95% confidence interval, 41-70%). Among 16 patients with measurable disease, the complete plus partial response rate was 75% (95% confidence interval, 54-96%). The complete plus partial response rate in 29 patients with nonmeasurable but evaluable disease was 45% (95% confidence interval, 27-63%) and an additional 14% had improvement in bone pain. Eight patients electively discontinued chemotherapy after 7-24 months of therapy, but continued aminoglutethimide. The median time to disease progression is 462 days (15.4 months); 25% of patients died by 552 days (18.4 months), and the median duration of survival is predicted to be 889 days (29.6 months). We conclude that aminoglutethimide can be combined with this doxorubicin-based regimen with acceptable toxicity and an overall response rate which is similar to that observed on prior ECOG trials with cyclophosphamide, doxorubicin, and 5-fluorouracil.
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PMID:A phase II evaluation of combination chemotherapy plus aminoglutethimide in women with metastatic or recurrent breast carcinoma. An Eastern Cooperative Oncology Group Pilot Study. 317 53

Forty-three consecutive patients with metastatic breast cancer and clearly measurable disease were treated with sequential multiagent chemotherapy. Therapy consisted of the administration in fixed sequence of cisplatin, doxorubicin, and cyclophosphamide (PAC) (four cycles), vinblastine, doxorubicin, and dexamethasone (VAD) (six cycles), and VP-16, methotrexate, and 5-fluorouracil (VMF) (six cycles). At the conclusion of 16 cycles of chemotherapy, all treatment was stopped. Patients were assessed for toxicity and disease response after each treatment. Duration of response and survival rate were determined for 41 evaluable patients. The overall response rate was 80% with 24% complete responses, 15% to PAC alone. Median duration of response (8 months) and median survival (17 months) were not superior to other reported multiagent chemotherapeutic programs. Toxicity included neutropenic fever, sepsis, renal failure, and electrolyte imbalance. Administration of sequential multiagent chemotherapy with a cisplatin-containing combination did not improve response rate, complete responses (CR), duration of response, or survival in this group of previously untreated breast cancer patients.
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PMID:Sequential multiagent chemotherapy incorporating cisplatin, doxorubicin, and cyclophosphamide in the treatment of metastatic breast cancer. 317 23

A phase II clinical trial was set up in metastatic breast cancer patients who had not received previous cytotoxic drug therapy, involving the administration of cis-dichlorodiammine platinum (cis-DDP). Patients aged up to 75 years and with pathohistologically confirmed disease were entered on the trial. All patients had measurable disease, a performance status (Karnofsky) of greater than 40, and an expected survival of greater than 6 weeks. In all 38 patients entered the trial, and 35 have been evaluated. The predominating metastatic sites included soft tissues (19), visceral organs (12), and bones (7 patients). cis-DDP was administered in a daily dose of 30 mg/m2 IV by a 4-h drip for 4 days, with customary hyperhydration. The results indicate a pronounced antitumorigenic effect of cis-DDP and a response rate of 54% (19/35), with 13 complete remissions (37%) and six partial remissions (17%). In terms of site the best response was obtained in soft-tissue processes (13/19; 68%), followed by visceral organs (4/10; 40%); the response rate was lowest in bones (2/6; 33%). The menopausal status and prior hormone therapy did not essentially influence the results of treatment, unlike previous irradiation. Patients with a lower performance status (40-70) had a significantly lower response rate (36% vs 63%; P less than 0.05). Toxic side-effects were moderate and did not substantially affect the general condition of the patients. A transient increase of serum creatinine was observed in 4 patients, and neurotoxicity in 2 patients. The results of the trial warrant the conclusion that cis-DDP has a pronounced antitumorigenic effect in untreated metastatic breast cancer, particularly in soft-tissue metastases. These results call for additional clinical study of the cytotoxic effect of cis-DDP in untreated metastatic breast cancer.
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PMID:Phase II clinical trial of cis-dichlorodiammine platinum (cis-DDP) for antitumorigenic activity in previously untreated patients with metastatic breast cancer. 668 1


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