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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based upon concepts derived from estrogen receptor studies, a phase II exploratory trial was conducted where tamoxifen (NSC-180973) was administered concomitantly with cytotoxic chemotherapy in postmenopausal patients with advanced breast cancer. Chemotherapy was composed of two 28-day cycles given alternatively. Cycle A consisted of adriamycin and vincristine, and cycle B consisted of cyclophosphamide, methotrexate, and 5-fluorouracil. Fifty-five patients were fully evaluable. Complete remissions were obtained in 13 (24%) and partial objective remissions in 27 (49%). The overall remission rate was 73%. Toxic side effects ranged from mild to severe. The most significant were nausea and vomiting (most patients), weakness and pain (two thirds of the patients), and hematologic changes (half of the patients). It is concluded that the present combination of endocrine and cytotoxic therapy represents one of the most effective currently available treatments of advanced breast cancer. In an early clinical trial of tamoxifen in premenopausal patients with advanced breast cancer, two objective remissions, lasting 5 and 9+ months respectively, were obtained in ten patients treated. Tamoxifen is worthy of further assessment in premenopausal patients.
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PMID:Current overview of EORTC clinical trials with tamoxifen. 102 Dec 27

Eight consecutive cases of open laparoscopic oophorectomy and salpingo-oophorectomy are reported. A modified technique that requires fewer specialized instruments and includes removal of the intact adnexa is demonstrated. Patients were not included if there was any suspicion of malignancy. Indications for surgery included chronic pelvic pain after hysterectomy (N = 5), endometriosis (N = 1), estrogen receptor-positive metastatic breast carcinoma that had not responded to chemotherapy (N = 1), and tuboovarian ectopic pregnancy (N = 1). No intraoperative or postoperative complications occurred. The average hospital stay was 1.1 days, and patients were released 3-14 days postoperatively. Five of the six patients with chronic pelvic pain had prompt resolution of their symptoms. In one patient who had a unilateral salpingo-oophorectomy, a contralateral procedure was required 3 months later because of continued chronic pelvic pain; her pain subsequently resolved. Laparoscopic salpingo-oophorectomy has the potential to decrease morbidity as compared with laparotomy in appropriately selected cases.
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PMID:Open laparoscopy simplifies instrumentation required for laparoscopic oophorectomy and salpingo-oophorectomy. 182 37

Estramustine phosphate, an anti-prostatic cancer agent, was investigated on eleven patients to evaluate the efficacy in a treatment of advanced breast cancers. The daily dose of medication was 840 mg. According to criteria of Japan Society for Cancer Therapy, none was assessed as CR, three as PR, four as NC and PD. The response rate was 27.3%. There was no differences in response rates among estrogen receptor status. A favourable response was observed in postmenopausal patients but no response in premenopausal, as well as a good response in lesions of soft tissue and lung, a poor response in lesions of liver and bone. As to toxicity of estramustine phosphate, gastrointestinal disorders such as nausea, vomiting and diarrhea were noted frequently during the treatment, and a long term administration was not able to perform in premenopausal patients because of vaginal bleeding and discharge, and pain in breast. The estramustine phosphate therapy for advanced breast cancers was regarded as one of modalities for a treatment of postmenopausal patients as a second line therapy. This is the first report in Japan discussing the efficacy of estramustine phosphate for a treatment of breast cancer.
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PMID:[Clinical evaluation of estramustine phosphate in the treatment of patients with advanced breast cancers]. 239 6

Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.
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PMID:Oral versus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. A randomized study of the Belgian Society of Medical Oncology. 294 41

Busramustine (KM-2210), the benzoate of a 17 beta-estradiol-chlorambucil conjugate, was administered to 11 patients with chronic lymphocytic leukemia (CLL) which included eight cases of B-cell CLL and three cases of T-cell CLL. Four patients had received prior chemotherapy. Busramustine was given orally at an initial daily dose of 50-100 mg continuously, and the dose was modified according to hematological improvement. Two cases of B-cell CLL achieved clinical complete responses, six cases including two of T-cell CLL and four of B-cell CLL achieved partial responses and one case of B-cell CLL achieved improvement. The partial and complete response rate was 72.7%. Four patients showed estrogen receptor activity of CLL cells ranging from 3.5 to 57.5 fmol/mg cytosol protein, but there seemed to be no correlation between the estrogen receptor activity of the CLL cells and the therapeutic effects of busramustine. Toxic effects included diarrhea (2/11) and estrogen-related symptoms including breast pain (4/11), genital bleeding (2/5), gynecomastia (2/6) and loss of libido (2/6). The findings of this preliminary study suggest that busramustine is effective in the treatment of CLL, irrespective of the presence of the estrogen receptor.
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PMID:Clinical response to busramustine (KM-2210) in chronic lymphocytic leukemia: a pilot evaluation of estrogen receptor in relation to its therapeutic effect. 320 82

This review covers eicosanoid metabolism in human uterine tissues, in normal menstrual cycles, menorrhagia, and IUD contraception. Since measuring tissue level of prostaglandins (PGs) leads to artifacts, recent studies have involved tissue culture, superfusion and histochemistry, to analyze arachidonic acid metabolism, in endometrium, its tissues, and myometrium. First, it was established that Pgf2alpha and PGE2 are the primary PGs elaborated by human endometrium. The enzyme that produces Pgf2alpha, cyclooxygenase, is located primarily in the glandular endothelium. Pgf2alpha is under estrogen receptor control. Progesterone reduces Pgf2alpha and antiprogestogens increase it. In normal menstrual cycles, both PGs are highest in late luteal phase. In women with menorrhagia, defined as menstrual blood loss over 90 ml, the Pgf2alpha:PGE2 ratio is abnormally low, a reasonable finding since Pgf2alpha is vasoconstrictive, and PGE2 is a vasodilator. Another vasodilator PG, prostacyclin or PGI2, may be abnormally high in women with excessive bleeding. Some experiments on endometrium and myometrium, cultured apart and together, suggest that there may be flow of substrates of the PG pathways such that less Pgf2alpha is available in this condition. Using radiolabelled arachidonic acid, researchers concluded that the Pgf2alpha pathway may be saturated because of substrate being incorporated into excess triglycerides, leading to alternative PG release. Another theory proposes that PG antagonist drugs which block menstrual pain may also lower synthesis of leukotrienes, an eicosanoid that causes vasoconstriction as well as inflammation and pain. There have been no studies comparable to the tissue culture work cited above concerning IUDs. Some explorations of leukocyte PG metabolism and the effects of copper are relevant to the conclusions about PGE2 as a vasodilator. There could also be an alteration of locally produced thromboxanes and prostacyclins on blood clotting in IUD wearers.
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PMID:The role of prostaglandins and allied substances in uterine haemostasis. 331 24

Usage of tamoxifen in the treatment of advanced breast cancer is increasing and is advocated by some authors as primary therapy in all estrogen receptor positive cancer patients. Tamoxifen is an incomplete estrogen antagonist with partial estrogen agonist activity as well. Tamoxifen-induced exacerbation of breast cancer ("tamoxifen flare") is reported to occur in 4-20% or more of treated patients. Management of this condition has varied from stopping treatment to continued administration or reinstitution of tamoxifen after flare symptoms subside. Responses have occurred in some patients so treated, although the remissions do not appear durable. The seven patients with advanced breast cancer in this report experienced disease exacerbation with tamoxifen therapy. Endocrine ablation afforded all patients excellent pain relief and disease control with prolonged survival in six of the seven. There have been no studies directly examining the disease course in flare patients continuing on tamoxifen. Persistence in treating these patients with an incomplete antagonist-agonist may deprive them of full survival benefit possible through ablative procedures when used in sequential treatment.
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PMID:Response of advanced breast cancer to total endocrine ablation after exacerbation on tamoxifen: results in seven patients and possible mechanism of action. 382 Nov 26

The skeleton is the most common organ to be affected by metastatic cancer, and tumors arising from the breast, prostate, thyroid, lung, and kidney possess a special propensity to spread to bone. Breast carcinoma, the most prevalent malignancy, causes the greatest morbidity. Of great clinical importance is the observation that metastatic bone disease may remain confined to the skeleton. In these patients, the decline in quality of life and eventual death is due almost entirely to skeletal complications and their subsequent treatment. Bone pain is the most common complication of metastatic bone disease, resulting from structural damage, periosteal irritation, and nerve entrapment. Recent evidence suggests that pain caused by bone metastasis may also be related to the rate of bone resorption. Hypercalcemia occurs in 5-10% of all patients with advanced cancer but is most common in patients with breast carcinoma, multiple myeloma, and squamous carcinomas of the lung and other primary sites. Pathologic fractures are a relatively late complication of bone involvement. The clinical courses of breast and prostate carcinoma are relatively long, with a median survival of 2-3 years. For patients with breast carcinoma, good prognostic factors for survival after the development of bone metastases are good histologic grade, positive estrogen receptor status, bone disease at initial presentation, a long disease free interval, and increasing age. In addition, patients with disease that remains confined to the skeleton have a better prognosis than those with subsequent visceral involvement. For patients with prostate carcinoma, adverse prognostic features include poor performance status, involvement of the appendicular skeleton and visceral involvement, whereas for patients with multiple myeloma, the levels of serum beta2-microglobulin and lactate dehydrogenase and the immunologic phenotype are the most important factors. These prognostic factors may be useful in planning the rational use of bisphosphonates in the treatment of advanced cancer.
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PMID:Skeletal complications of malignancy. 936 26

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.
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PMID:Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study. 982 25

Breast cancer patients frequently develop bone metastasis. Parathyroid hormone-related protein, an osteoclast activating factor, might be necessary for tumorto erode bone and grow at skeletal site. Bisphosphonates have an affinity for bone and are potent inhibitors of osteoclastic bone resorption. In light of this,53 patients with bone metastasis from breast cancer were treated with chemoendocrine(mainly high-dose medroxyprogesterone acetate as the endocrine therapy) therapy + bisphosphonate (pamidronate, Aredia (R)). During the previous 6 years (median 27 months), 53 breast cancer patients with bone metastasis were treated with pamidronate + chemoendocrine therapy. The regimen consisting of pamidronate + chemoendocrine agent was administered to 27 patients as a post relapse first-line regimen and to the remaining 26 cases, which failed first- or second-line treatment as a second or third line regimen. As a result of the combination therapy, sclerotic changes were observed in the osteolytic lesions in 31 of the 53 patients (59%). The effect on the osteolytic lesions did not correlate with the duration of disease free interval, estrogen receptor (ER) status, presence/absence of previous therapy or number of " hot spot(s) ] on bone scintigraphy. Lessening of pain from the bone metastasis was achieved in 83% of the patients after 3 months of pamidronate administration. Pamidronate + chemoendocrine therapy seems highly promising.
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PMID:New Treatment Strategy for Bone Metastases from Breast Cancer. 1109 32


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