Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Recent reports have suggested that the sensitivity to chemotherapy of endocrine-dependent breast cancer may be enhanced by transient exposure to hormonal stimulation. To test this concept, 39 postmenopausal women with proven metastatic breast carcinoma and measurable disease were entered into this prospective, double-blind trial; 35 are currently evaluable. All patients were continuously treated with aminoglutethimide and hydrocortisone to lower estrogen production, plus cyclic chemotherapy. Patients in the "stimulation" arm received in addition, Estrace 2 mg b.i.d. sublingually for 3 days before and on the day of chemotherapy. Estrace administration appeared to accelerate tumor growth as demonstrated by increased bone pain, hypercalcemia, and growth of skin lesions. Response rates, response duration, and survival were similar in the stimulation and control groups.
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PMID:A randomized trial of aminoglutethimide +/- estrogen before chemotherapy in advanced breast cancer. 354 14

Between 1972 and 1979, forty-six women underwent endocrine ablative surgery, having failed combinations of chemotherapy, radiation, and surgery (including oophorectomy). All had clinically measurable disease; nearly half were afflicted with bone pain. Each was judged to be a candidate for the procedure by estrogen receptor studies (52%), response to L-dopa (39%), or response to prior oophorectomy (8%). All were followed to their death or to the present, with a minimum of 12 months for those alive. Thirty-one (67%) were improved, and disease was arrested in five (11%) for a median time of 13.5 months. There was no difference in response rates or intervals between estrogen receptor-positive and L-dopa-positive groups. Response was not correlated with disease-free interval or menopausal status. Best results were achieved in those with metastases confined to an organ system, particularly the skeletal complex. The procedure is withheld in those with brain metastases. Postablative chemotherapy appeared to prolong the control interval, though numbers are small. The low morbidity and mortality (one death) of midline adrenaloophorectomy combined with the high incidence of recapture of disease leads us to recommend this procedure in appropriately selected patients who have previously failed other therapeutic modalities.
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PMID:Endocrine ablation in breast cancer patients who have failed cytotoxic therapy. 731 51

To our knowledge, no standard chemotherapy for patients with hormone-refractory prostate cancer (HRPC) has been established. Since most patients with HRPC are elderly and have bone metastasis, cytotoxic chemotherapy causes them to be at high risk for myelosuppression. Therefore, chemotherapeutic agents with low toxicity and good compliance should be elected. We conducted three regimens for HRPC on an outpatient basis. Eligibility criteria were defined as serial rising PSA values on 3 or more occasions at least 2 weeks apart or radiological new or extensive lesions under hormonal therapy. The first regimen is comprised of cyclophosphamide (CPM), 100 mg/day, UFT, 400 mg/day, and estramustine phosphate (EMP), 560 mg/day in two daily fractions. The second regimen is comprised of an oral administration of dexamethasone (DEX) (0.5-2 mg/day). The third regimen is comprised of DEX, 1 mg/day, cyclophosphamide, 100 mg/day and UFT, 400 mg/day in two daily fractions. Post-therapy prostate-specific antigen (PSA) level in serum, objective response on bone scan or measurable disease, and symptomatic response on bone pain were assessed. All regimens showed clinical efficacy with mild toxicity. Indications and limitations of these regimens are discussed. Further, the combination trials of taxane and EMP in patients with HRPC are reviewed.
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PMID:[Hormonal chemotherapy for hormone-refractory prostate cancer]. 1251 47