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)

Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.
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PMID:A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer. 191 Dec 4

New approaches are needed in the treatment of advanced breast cancer. In vitro studies have shown that recombinant tumor necrosis factor (TNF) is a growth inhibitor for the MCF-7, ZR-75-1, and BT-20 human breast cancer cell lines. Based on these considerations, the Southwest Oncology Group performed a Phase II trial of recombinant TNF (Genentech) (150 micrograms/m2) given by 30-minute intravenous infusion on days 1 to 5 of every other week for 8 weeks. Patients with metastatic breast cancer who had received one prior chemotherapy regimen for advanced disease were eligible. Of the 22 patients who were entered, 3 were ineligible. Nineteen patients who had a performance status of 2 or less could be examined (median age, 53 years). One possible fatal toxic reaction has been seen in a patient who had intracranial bleeding caused by a previously undiagnosed brain metastasis; no other treatment-related deaths have occurred. Toxicity has included nausea, vomiting, fever, chills, myalgia, and fatigue. No Grade 4 toxicity has been observed. Grade 3 toxic reactions have included hypotension (two patients), diarrhea (one patient), transient leukopenia (two patients), and reversible elevations of liver function test values (two patients). No objective responses have been observed. Twelve of 19 patients have died (median survival time, 8.5 months). Recombinant TNF is inactive as a single agent in patients with previously treated metastatic breast cancer.
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PMID:A Southwest Oncology Group phase II Trial of recombinant tumor necrosis factor in metastatic breast cancer. 191 10

Experimental models have demonstrated the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-potentiating activity of lonidamine. Phase II clinical trials on advanced breast cancer have shown that this drug induced a 16% objective response rate. Present multicentric randomized trial was conducted to verify whether lonidamine can potentiate the antineoplastic effects of conventional fluorouacil, Adriamycin, cyclophosphamide (FAC) chemotherapy in advanced breast cancer. From January 1987 to December 1989, 265 patients were enrolled in this study, and 231 are evaluable for response. After stratification according to institution and ECOG performance status (PS), the patients were randomly allocated to receive either standard FAC therapy (group A) or FAC plus lonidamine (600 mg orally daily three times a day) (group B). After three FAC courses, the patients with no progressive disease were further randomized to either receive continuous treatment up to the time of tumor progression (maximum: 10 courses) or to discontinue therapy when a response "plateau" was reached. In this latter group, the same therapy was restarted at relapse or disease progression. Objective response (complete response plus partial response) was significantly higher in group B (66.3%) compared to group A (42.3%). The actuarial median times to disease progression was also significantly longer (P less than 0.0001) in group B (median 9 months) than in group A (median 6 months). Other than myalgia and gastric pain, no increased toxicity was observed in the lonidamine. The analysis of second randomization are yet available because of the longer follow-up time required. Present findings suggest an interesting additive effect of lonidamine when combined with FAC chemotherapy and warrant further investigation in other therapeutic regimens and in other neoplastic diseases.
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PMID:Fluorouracil, doxorubicin, and cyclophosphamide versus fluorouracil, doxorubicin, and cyclophosphamide plus lonidamine for the treatment of advanced breast cancer: a multicentric randomized clinical study. 203 Dec 1

Thirty-two patients with advanced breast cancer were treated with mitomycin-C 10 mg/m2 IV and vinblastine 6 mg/m2 IV every 21 days in combination with lonidamine 450 mg/day P.O. and prednisone 15 mg/day P.O. given continuously. Among the 29 evaluable patients (all but three pretreated with an anthracycline-based regimen), one complete remission (CR) and six partial remissions (PR) (response rate, 24%) were seen. The median duration of response was 14 months (range, 4-30 months). Median survival for responders was 18 months (range, 4-30 months). Hematological toxicity was uncommon; the main lonidamine-related side effects were myalgia, abdominal cramps, and reversible deafness; these side effects were severe in two, one, and one patients, respectively. The regimen seems to have a reasonable degree of activity and toxicity in advanced, refractory breast cancer. The role of lonidamine in the treatment of this disease warrants further evaluation.
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PMID:Mitomycin-C, vinblastine, and lonidamine as salvage treatment of advanced breast cancer. A pilot study. 212 16

This paper describes Phase I clinical studies of Antineoplaston A2 injections. The studies involved 15 patients diagnosed with advanced neoplastic diseases including cancers of the breast, bladder, lung, kidney, oesophagus, colon and liver, mesothelioma and glioma. Antineoplaston A2 was administered in divided doses daily intravenously through a subclavian vein catheter. The treatment was given from 53 to 358 days. The highest dosage administered was 147 mg/kg/24 h. Only minimal adverse effects were noticed sometime during the treatment, including fever, chills and myalgia. Desirable side-effects included increase of platelet and white blood cell counts, hypertrophy of epidermis and decrease of cholesterol and triglyceride levels. Nine patients showed objective response to the treatment. Cases of complete remission included adenocarcinoma of the lung, mesothelioma, metastatic liver and bladder cancers. In an additional case of breast cancer, the patient obtained complete remission of liver metastasis and stabilization of bone metastases. Partial remission was accomplished in cancers of the breast and oesophagus. Three patients, including cases of adenocarcinoma of the lung, mesothelioma and bladder cancer, were in complete remission for over five years.
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PMID:Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. 356 10

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of lonidamine, given in an escalating oral daily schedule to a maximum dose of 450 mg/m2 in patients with previously treated advanced breast cancer. Five responses were seen in 30 evaluable patients (17%). Treatment was discontinued because of toxicity in seven patients. Toxicity generally consisted of myalgia, nausea, vomiting, skin hyperesthesia, somnolence, and ototoxicity. All side effects were reversible and no hematologic toxicity was observed. The absence of myelosuppression and the suggestive lack of cross-resistance between lonidamine and standard chemotherapeutic drugs warrant further studies of lonidamine in breast cancer, particularly in combination with other agents.
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PMID:Phase II study of lonidamine in patients with metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group Study. 376 73

15 patients with metastatic cancer were treated with Lonidamine, a substituted indazole carboxylic acid active against the Lewis lung and Sarcoma 180 tumors. Single doses of 600 mg (350-400 mg/m2) mostly induced somnolence and gastro-intestinal side effects. Toxicity occurring during chronic administration of Lonidamine at doses ranging between 45 and 275 mg/m2 twice daily, mainly consisted of somnolence, myalgias, hyperesthesia and mild hair loss. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. In 1 patient with breast cancer resistant to standard chemotherapeutic agents, a 30% reduction of measurable tumor masses was seen. In view of the lack of overlapping toxicity between Lonidamine and other chemotherapeutic drugs, and of its potential activity, it is suggested that phase II studies of Lonidamine be initiated at a dose of 135 mg/m2 twice daily.
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PMID:Phase I toxicologic study of Lonidamine in cancer patients. 671 96

12 patients with metastatic cancer were treated with the substituted indazole carboxylic acid Lonidamine at oral daily doses of 270 mg/m2. Toxicity, consisting mainly of myalgias, somnolence, hyperesthesia, anorexia and vomiting, generally decreased or disappeared over time despite continuing drug administration at unmodified dosage. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. Partial responses were observed in a patient with hypernephroma and in a patient with breast cancer. Disease-oriented phase II studies with this new anticancer agent are warranted.
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PMID:Phase II study of Lonidamine in cancer patients. 671 98

Lonidamine, a substituted indazole carboxylic acid with unique effects on cellular respiration, was studied in 27 patients with advanced malignancies. Of the 18 evaluable patients, 5 had small-cell lung cancer, 3 had non-small-cell lung cancer, 3 sarcoma, 2 breast cancer, and 5 other tumour types. All but 1 had had extensive prior treatment. A partial response was seen in 1 patient with metastatic synovial sarcoma, and tumour growth inhibition was demonstrated in 2 other cases. The major toxicity encountered was myalgia (66.6%) which was incompletely ameliorated by prednisone and required dose reduction in 2 patients and cessation of drug in 3. Other toxicities included auditory changes, anorexia, nausea and vomiting, diarrhoea, skin sensitivity, and conjunctivitis. No added toxicity was seen, when Lonidamine was combined with other chemotherapeutic agents. No correlation between Lonidamine dose and serum lactate levels was seen, although 4 patients showed a progressive increase in lactate levels over time, thought to be related to their increasing tumour burden. 5 patients demonstrated a dramatic fall in serum testosterone levels 4-8 weeks after starting Lonidamine which was accompanied by an increase in luteinizing hormone levels in 3 patients. In summary, modest antitumour activity was demonstrated in 3 patients; moderate toxicity was seen in most patients, but was usually tolerable. Further studies of Lonidamine are warranted in less heavily treated patients, alone or in combination with other chemotherapeutic agents.
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PMID:Phase II evaluation of Lonidamine in patients with advanced malignancy. 671 99

Lonidamine was studied in advanced cancer patients. The drug was given orally by single or repeated administrations. Single doses ranged from 150 to 450 mg. Repeated administrations were performed with progressively increasing doses: 450-900 mg daily. Lonidamine lacked severe toxic effects after both single and prolonged administrations. The most common side effect was myalgia; gastrointestinal discomfort was also reported. 1 patient with lung cancer experienced an episode of arrhythmia which subsided upon discontinuation of treatment and did not reoccurr++ when treatment was reinstated. 1 partial and 2 minor responses were observed in the 6 patients with breast cancer.
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PMID:Early observations on the administration of Lonidamine in cancer patients. 671


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