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)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

During the phase I study of maytansine at our institution, some activity was observed against breast carcinoma and melanoma. A phase II study was thus initiated to more thoroughly investigate the activity of this drug against these two tumors. In 33 evaluable patients with melanoma, no complete or partial responses were observed. Twenty-one evaluable patients with breast cancer were entered and only one response (partial) was seen. The toxicity was similar to that observed in the phase I study and consisted mainly of diarrhea, paresthesias, phlebitis, and flu-like symptoms. Myelosuppression was infrequent and was short-lived when it occurred.
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PMID:Results of a phase II study of maytansine in patients with breast carcinoma and melanoma. 37 3

A randomized clinical trial, involving approximately 100 patients, that compared two combination therapy regimens (5 FU, methotrexate, vincristine, cyclophosphamide with and without prednisone) in advanced breast cancer showed a significantly higher rate of response for the 5-drug therapy group (62.5 versus 44.2%). However, no significant difference in survival has been observed to date. Some differences in toxicity were observed, e.g. a significantly greater number of cases with mild diarrhea for the 5-drug regimen, and a few more cases of sensory loss (not significant) and significantly more severe leukopenia (p value 0.06) for the 4-drug regimen.
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PMID:Combination chemotherapy in breast cancer: a randomized study of 4 versus 5 drugs. 122 26

Topoisomerase I represents a unique new target that can be exploited for development of new antineoplastic agents. There are now two new topoisomerase I inhibitors that are in early clinical trials that have generated a tremendous amount of interest. Topotecan (SKF 104864-A) is a topoisomerase I inhibitor that has been explored in phase I trials using a variety of dosages and schedules. The dose-limiting toxicity of the agent is neutropenia. Other toxicities include alopecia, very mild nausea and vomiting, anemia, and occasional fever. Responses have already been noted in patients with advanced, refractory ovarian cancer and non--small-cell lung cancer. The drug is currently undergoing intense phase II testing. Irinotecan (CPT-11) is also a topoisomerase I inhibitor, which has already undergone extensive phase I and early phase II clinical testing in both Japan and the United States. Dose-limiting toxicities of the agent have included neutropenia and diarrhea. Responses have been noted in patients with refractory colorectal cancer, non--small-cell lung cancer, lymphoma, ovarian cancer, head and neck cancer, pancreatic cancer, and breast cancer. There is no doubt both of these agents will be important additions to our chemotherapy armamentarium.
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PMID:Clinical trials with the topoisomerase I inhibitors. 133 79

A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer was done at 31 institutions in Japan. Forty-five patients were registered and 44 of them were eligible for the study. Of the 40 patients whose results could be evaluated, 11 (28%) responded (four complete responses and seven partial responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver dysfunction were observed in 24 of the 44 patients. The side effects were mild and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its tablet form makes chemotherapy easier for the patient.
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PMID:[Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31 institutions]. 138 88

Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy.
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PMID:Metastatic breast carcinoma presenting as persistent diarrhea. 143 49

Rhizoxin is a 16-membered antifungal macrocyclic lactone isolated from the plant pathogenic fungus Rhizopus chinensis. The compound binds to tubulin, preventing microtubule formation, and inhibiting mitosis. It possesses antitumour activity in vivo against various preclinical murine models, both leukaemias and solid tumours model, as well as in vincristine- and doxorubicin-resistant leukaemia lines. In the present study, cytotoxic activity was observed in human tumour cell lines in vitro at very low concentrations (+/- 10(-10) M) particularly against melanoma, colon, renal, non-small cell and small cell lung cancer. In vivo antitumour activity was demonstrated in murine P388 and L1210 murine leukaemias, solid tumour models B16 melanoma and M5076 sarcoma, and in 5 out of 9 human solid tumour xenografts: LOX melanoma, MX-1 breast cancer, non-small cell lung cancer A549, and small cell lung cancers LXFS 605 and LXFS 650. The absence of cross-resistance to vinca alkaloids was confirmed in vivo against the vincristine-resistant P388 leukaemia subline and the vincristine-resistant human small cell lung cancer LXFS 650. In addition, the antitumour activity of rhizoxin was improved by prolonged or repeated drug administration indicating a schedule dependency. In animal toxicology studies, transient changes in erythrocyte and leukocyte numbers, local phlebitis, diarrhea, and spermatogenic arrest were observed. The LD10 value of rhizoxin after a single intravenous injection was 2.8 mg/kg (8.4 mg/m2). One-tenth of the mouse equivalent LD10 (0.84 mg/m2), the starting dose for clinical phase I studies, was considered to be safe in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical antitumour activity and animal toxicology studies of rhizoxin, a novel tubulin-interacting agent. 145 59

A 54 year-old female patient with disseminated breast cancer refractory to various kinds of previous therapies was treated with a combination therapy of 5'-DFUR, MPA and CPA. Partial response (PR) was obtained both against pleural and liver metastases with complete disappearance (CR) of soft tissue lesions and was still being continued for the following 7 months. No serious side effects were observed except for a mild degree of diarrhea and moon face. The patient was enjoying a favorable quality of life. We confirmed that this combination regimen was effective as the second line treatment for disseminated breast cancer.
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PMID:[Successful treatment of disseminated breast cancer with combination therapy of 5'-deoxy-5'-fluorouridine (5'-DFUR), medroxyprogesterone acetate (MPA) and cyclophosphamide (CPA)]. 153 Sep 5

The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with incurable, metastatic or locally advanced breast cancer. While no prior chemotherapy for metastatic disease was permitted, prior adjuvant chemotherapy was allowed provided that no anthracycline or anthracene had been given. Forty-eight patients were evaluable for response. Two patients (4%) achieved complete remissions, 9 patients (19%) achieved partial remissions, 26 patients (54%) were stable and 11 patients (23%) failed. At the initial menogaril dose of 275 mg/m2 per week, 13 of 14 patients required a dose reduction and/or a treatment delay of one or more weeks. Therefore, the menogaril dose was reduced to 225 mg/m2 per week for the last 37 patients. At that those, 20 of 37 patients developed grade 3 or 4 granulocytopenia and 22 required dosage delays. At the initial starting dose, the average dose intensity actually delivered was 169 mg/m2 per week. At 225 mg/m2 the average dose intensity actually delivered was 197 mg/m2 per week. Toxic effects included mild to moderate nausea and vomiting, diarrhea, hair loss and occasional hyperpigmentation. In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer.
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PMID:Phase II study of oral menogaril as first line chemotherapy for advanced breast cancer: a National Cancer Institute of Canada Clinical Trials Group study. 153 20

Seventy-five female patients suffering from advanced breast cancer were treated with toilet mastectomy, radiotherapy and oophorectomy (if premenopausal) or tamoxifen therapy (if postmenopausal) as well as chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil and prednisone. The most common side-effects of combined chemohormonal therapy were gastro-intestinal (nausea, vomiting, rarely diarrhoea) in 43 patients (57.3%), followed by alopecia in 23 patients (30.6%), myelosuppression in 12 patients (16%), extravasation and thrombophlebitis in 7 patients (9.3%), and mucositis and oral erythema in 3 patients (4%). Side-effects of tamoxifen therapy such as vaginal discharge, bleeding, hot flushes were encountered in 10 patients (13.3%). Hypercalcaemia, tumour flare and hepatic, renal, cardiac, pulmonary and neurological toxicities were not encountered. Improvement of 10-30% in Karnofsky performance status was noted in responders while 20-30% deterioration was observed in non-responders. Combination therapy was mostly well tolerated, side-effects were few and toxicities were temporary and reversible.
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PMID:Toxicity and side-effects of combination chemohormonal therapy of advanced breast cancer. 158 18


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