Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-six outpatients with breast cancer who had experienced severe emesis as a result of chemotherapy were evaluated for the antiemetic efficacy of high-dose metoclopramide (HD-MCP) and dexamethasone (DXM). Chemotherapy consisted of: cyclophosphamide 600, methotrexate 40 and 5-fluorouracil 600 mg/m2 (CMF) given intravenously every 3 weeks. The dosage of antiemetic drugs was MCP 2 mg/kg and DXM 0.2 mg/kg given by slow intravenous drip 0.5 h before the administration of chemotherapy. 138 courses of combined chemotherapy--HD-MCP and DXM--were administered, with a mean of 3 courses and a range of 1-10 courses per patient. Complete protection--no nausea and no vomiting--was achieved in 17.7% of the courses. Partial protection--no vomiting with mild nausea or 1-3 episodes of vomiting--in 45.3% of the courses. The total antiemetic efficacy was 63%. The most common side effects were: drowsiness, dry mouth, restlessness and diarrhea. Sixteen patients (35%) refused to continue the antiemetic regimen because of the side effects. HD-MCP and DXM have antiemetic efficacy, but because of these side effects, further studies are required to determine the optimal dose of each of these drugs.
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PMID:High-dose metoclopramide and dexamethasone as an antiemetic in outpatients receiving chemotherapy for breast cancer. Second study. 361 13

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.
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PMID:Multicenter study of trilostane: a new hormonal agent in advanced postmenopausal breast cancer. 369 May 30

The new anthracycline-analogue 4-demethoxydaunorubicin (4-DMDR) was administered orally at the dose of 15 mg/m2 daily for three consecutive days and repeated every 21-28 days on 29 patients with advanced pretreated breast cancer. A partial remission was observed in 7/25 evaluable patients (28%) for a median duration of 7 months. Side-effects include leukopenia in 93% of the patients (less than 1000 WBC/mm3 in 7%), nausea in 41%, mild vomiting in 17%, diarrhea in 10% and alopecia in 10% of the patients. No definitive conclusion is possible regarding cardiotoxicity. Only mild changes in ECG were observed in two patients. This study shows that 4-DMDR administered orally is well tolerated in the majority of patients and has antitumor activity in advanced breast cancer.
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PMID:Activity of 4-demethoxydaunorubicin by the oral route in advanced breast cancer. 386 82

Vinzolidine, a semisynthetic vinca alkaloid, was studied as oral therapy in 30 patients with Kaposi's sarcoma, non-small cell lung cancer, colorectal cancer, and breast cancer. Substantial variations in morbidity were observed among the patients, some patients receiving doses up to 45 mg/m2 without toxicity while others had severe hematologic toxicity at doses as low as 25 mg/m2. Nausea/vomiting and diarrhea also occurred. Responses were seen in two of 11 patients with Kaposi's sarcoma but not in other patients. Unpredictable severe hematologic toxicity led to early closure of this study. The heterogeneity of patient tolerance may relate to variable oral drug bioavailability, and it is conceivable that vinzolidine could be administered more safely by the IV route.
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PMID:Oral vinzolidine as therapy for Kaposi's sarcoma and carcinomas of lung, breast, and colon/rectum. 396 55

Eighteen patients with advanced breast cancer refractory to first-line chemotherapy and hormonal therapy (or estrogen receptor-negative) were treated with human alpha-lymphoblastoid interferon (Wellferon) in a dose of 30 X 10(6) U/m2 im weekly. None of 15 patients receiving three or more doses achieved a partial or complete response. Toxicity was substantial and included fatigue, malaise, fever, hematologic suppression, nausea/vomiting, and diarrhea.
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PMID:Phase II trial of alpha-lymphoblastoid interferon given weekly as treatment of advanced breast cancer. 400 77

Twenty-nine evaluable patients with extensively pretreated breast cancer received PALA, a new pyrimidine antimetabolite. The drug was given by intravenous infusion over 60 min, at a daily dose of 2.5 g/m2 for 2 consecutive days. Courses were repeated at 2-week intervals and doses were escalated to toxicity. Two objective partial remissions were observed, lasting for 3 and 4.5 months respectively. Toxic effects were dose-related and consisted mainly of mucocutaneous manifestations, i.e., skin rashes, stomatitis, diarrhea, conjunctivitis and corneal ulcerations. Evidence of antitumor potential in far-advanced disease and lack of myelosuppression point to the need for additional trials of PALA in a more favorable selection of patients with breast cancer.
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PMID:N-(phosphonacetyl)-L-aspartate (PALA) in advanced breast cancer: a phase II trial of the EORTC breast cancer cooperative group. 621 61

Ten women with skeletal metastases from breast carcinoma received dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, in a placebo-controlled, double-blind, crossover study. Eight of these patients had either hypercalcemia or hypercalciuria, and all 10 had elevated urinary hydroxyproline levels as evidence of active skeletal disease. Eight patients had moderate to severe bone pain. After eight weeks of oral dichloromethylene diphosphonate treatment (3,200 mg per day), either preceded by or followed by an eight-week placebo period, seven of eight patients with hypercalciuria had significant reductions in urinary calcium levels, and nine of 10 had reductions in urinary hydroxyproline levels (significant in eight) when the dichloromethylene diphosphonate treatment periods were compared with prestudy or placebo periods. Additionally, seven of eight subjects had decreased pain with dichloromethylene diphosphonate. There were no adverse effects other than transient diarrhea in some patients. We conclude that oral dichloromethylene diphosphonate can significantly inhibit osteoclast-mediated bone destruction in patients with bone metastases from breast cancer.
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PMID:Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton. 621 77

Clinical efficacy of new fluorouridine derivative, FF-705, was studied in 108 patients with advanced malignant tumors. Partial responses were observed in 8 of 61 evaluable cases (13.1%): 4 of 9 patients with breast cancer, 1 of 19 patients with gastric cancer, 1 of 15 patients with lung cancer, 1 of 3 patients with kidney cancer and 1 of 1 patient with pancreas cancer. In the analysis of adverse effects of FF-705, gastrointestinal toxicity was major toxicity. Especially, diarrhea was observed in 41 of 108 patients (38.0%) within a total dose of 10 g shortly after drug administration.
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PMID:[Phase II study of FF-705 by Clinical Cooperative Study Group]. 623 55

Complete remissions in patients with advanced breast cancer using either endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor (ER) status, and the low complete remission rate may be secondary to this biochemical heterogeneity. Laboratory experiments using breast cancer cells in long-term tissue culture revealed that tamoxifen is cytotoxic, estrogen stimulates the growth of ER-positive cells and can rescue cells from tamoxifen's effect, and sequential MTX/5-FU is synergistic in rapidly growing breast cancer cells. Based on this, a phase II protocol was designed using tamoxifen, 10 mg p.o. b.i.d. for days 1 to 10. This was followed by Premarin, 0.625 mg p.o. b.i.d., on days 11 to 14. On day 14 the patients were given MTX, 200 mg/m2 i.v., followed in 1 hr by 5-FU, 600 mg/m2 i.v. The patients were rescued with leucovorin, 10 mg/m2 24 hr later. This dose of leucovorin was repeated every 6 hr for six doses. The cycle is repeated every 18 days. Thus far, 35 patients have been entered and 32 are currently evaluable for response. The median age is 57 years. The median Karnofsky performance status was 90. Of the 35 patients, 63% were ER-positive, and 23% had received prior endocrine therapy or chemotherapy; 71% were postmenopausal. One third of the patients had visceral-dominant disease. The overall response rate was 69%; 15 of 32 (47%) attained a complete remission, and 7 of 32 (22%) had a partial remission. Toxicity was minimal. Median nadir white blood cell counts were 5600/cu mm, and median nadir platelet counts were 252,000/cu mm. Nausea and vomiting occurred in 25% of patients, but there was no hair loss, rash, or diarrhea. Mucositis was rare. In summary, this combination hormonal-chemotherapy regimen is highly effective with a high complete remission rate and minimal toxicity.
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PMID:Methotrexate and 5-fluorouracil following tamoxifen and premarin in advanced breast cancer. 630 35

Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.
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PMID:Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer. 636 39


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