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)

We aimed to determine the efficacies of a non-anthracycline-containing regimen, docetaxel/capecitabine (TX), in comparison with an anthracycline-containing regimen, doxorubicin/cyclophosphamide (AC), as primary chemotherapy for node-positive early stage breast cancer. In this phase-III single center randomized study, we randomized 209 women with axillary node positive, stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy. The primary endpoint was tumor pathologic complete response (pCR). Clinical response rates, toxicity profiles, disease free survival (DFS), and overall survival were secondary objectives. In total, 204 patients had clinical and radiological evaluation of response, and underwent surgery. Compared with AC, TX increased pCR in primary tumors (21% vs. 10%, respectively, P = 0.024) and clinical response (84% vs. 65%, P = 0.003). TX was associated with less nausea and vomiting, but more stomatitis, diarrhea, myalgia, and skin/nail changes than AC. With a median follow-up of 37 months, there was no significant difference in DFS by treatment groups (P = 0.932). Fewer patients developed recurrence who achieved pCR in lymph node (LN) (P = 0.025; hazard ratio, 0.189; 95% CI, 0.044-0.815) in the multivariate analysis. TX showed superior efficacies to AC with increased pathologic and clinical complete response rates. Although these findings did not translate into a gain in DFS, the patients who achieved pCR in LN developed significantly less recurrence.
Breast Cancer Res Treat 2008 Jun
PMID:A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. 1765 51

Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile limits treatment duration to 5 years. Increased efficacy over tamoxifen and good tolerability have recently made the third-generation aromatase inhibitors (AIs) the first-choice agents for adjuvant endocrine therapy; however, it is currently not known whether AI therapy, like tamoxifen, will be limited to 5 years. Many side effects of endocrine therapy, such as hot flushes and mood disturbances, are related to estrogen deprivation and are common to tamoxifen and AIs, reflecting the mechanism of action of these drugs. In addition, tamoxifen has estrogenic effects that are beneficial in some tissues: tamoxifen lowers serum cholesterol levels and protects against bone loss and cardiovascular disease, but is also associated with potentially life-threatening side effects, such as endometrial cancer and thromboembolic disease. As AIs lack estrogenic activity, they are not associated with these serious adverse events. Clinical trials comparing AIs with tamoxifen in the adjuvant setting have shown that AIs are well tolerated and are associated with a lower incidence of gynecological symptoms and hot flushes than tamoxifen. However, AIs are associated with musculoskeletal side effects, such as arthralgia, myalgia and bone loss, but these events are preventable or manageable. The effects of AIs on lipid metabolism and the cardiovascular system are still debatable, but placebo-controlled trials provide no evidence to suggest that AIs adversely affect these systems. Furthermore, the AIs allow women to maintain a good quality of life, comparable with women receiving tamoxifen or placebo, and are a cost-effective therapeutic option. Ongoing trials will provide more information regarding the long-term effects of AI therapy and will provide comparative data on the efficacy and safety of the different AIs, thereby helping to determine the optimal treatment strategy for these highly effective and well-tolerated drugs.
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PMID:Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer. 1789 Feb 11

The major toxicities associated with paclitaxel(PTX)-based chemotherapy are myelosuppression, peripheral neuropathy and myalgia/arthralgia. In the present study, a retrospective study was carried out to compare the incidence of adverse events during PTX-based chemotherapy between 58 cases treated every 3 weeks(tri-weekly regimen)for breast cancer and non-small cell lung cancer and 47 cases with weekly regimen for breast cancer and gastric cancer. Hematological toxicity such as neutropenia and thrombocytopenia, peripheral neuropathy and myalgia/arthralgia occurred more frequently in patients with a tri-weekly regimen than in those with a weekly regimen(grade 3/4 neutropenia: 65.5% versus 12.8%, odds ratio; 12.98, grade 2/3 peripheral neuropathy: 24.1% versus 6.4%, odds ratio; 4.67, and grade 2/3 myalgia/arthralgia: 43.1% versus 4.3%, odds ratio; 17.05). The development of peripheral neuropathy and myalgia/arthralgia was dependent on the dose per injection, but not on the cumulative dose of PTX. The initial onset of peripheral neuropathy and myalgia/arthralgia was observed in more than 80% of patients during the first course of the tri-weekly regimen, while it was seen in any course of the weekly regimen. The incidence of other nonhematological adverse events was not different between the two regimens except for nausea. Our present findings suggest that the peripheral neuropathy and myalgia/arthralgia are highly frequent adverse events that depend on the dose per injection of PTX, in which the incidence was more frequent in the tri-weekly than in the weekly regimen.
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PMID:[A retrospective analysis of adverse events based on a dose and a schedule in patients who underwent paclitaxel- containing chemotherapy]. 1893 76

For the medical treatment of early breast cancer, aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane are more effective than selective estrogen-receptor modulators (SERMs) such as tamoxifen (TAM). However, the adverse events associated with AIs are different from those associated with SERMs. Hot flushes, gynecological disorders, and thrombosis are more frequent in patients treated with TAM than in those treated with AIs. Conversely, osteoporosis, fractures, joint symptoms, and myalgia are more common in patients receiving AIs. Osteoporosis and bone fractures resulting from osteoporosis are important issues for patients treated with AIs. The precise management of bone health, in strict accordance with clinical guidelines, is vital in patients receiving AIs. AI-related joint symptoms are also one of the most important considerations for patients taking AIs. AI-related joint symptoms are the most common reason for the discontinuation of AIs. Confirmed management strategies for AI-related joint symptoms are unavailable at present. In patients receiving AIs, long-term adverse events (for example, those occurring as a result of changing lipid metabolism) remain unclear. There is a clear need to elucidate AI-related adverse events over the long term and to establish management strategies for AI-related adverse events, such that AIs can be used safely in patients with breast cancer over long periods of time.
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PMID:Safety profiles of aromatase inhibitors and selective estrogen-receptor modulators in the treatment of early breast cancer. 1894 48

Breast cancer survivors (BCSs) on aromatase inhibitor (AI) therapy often experience musculoskeletal symptoms (joint pain and stiffness, bone and muscle pain, and muscle weakness), and these musculoskeletal symptoms may be related to low serum levels of vitamin D. The primary purpose of this pilot exploratory study was to determine whether serum levels of 25-hydroxyvitamin D (25[OH]D) concentration were below normal (<30 ng/mL) in 29 BCSs on AI therapy and if musculoskeletal symptoms were related to these low vitamin D levels. The mean (SD) serum 25(OH)D level was 25.62 (4.93) ng/mL; 86% (n = 25) had levels below 30 ng/mL. Patients reported muscle pain in the neck and back, and there was a significant inverse correlation between pain intensity and serum 25(OH)D levels (r = -0.422; P < .05 [2 tailed]). This sample of BCSs taking AIs had below normal levels of serum 25(OH)D despite vitamin D supplements. This is one of the few studies to document a significant relationship between vitamin D levels and muscle pain in BCSs on AI therapy. Findings from this pilot study can be used to inform future studies examining musculoskeletal symptoms in BCSs on AI therapy and relationships with low serum levels of vitamin D.
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PMID:Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. 1912 20

Ixabepilone is a novel microtubule-stabilizing agent with clinical efficacy in advanced breast cancer, including patients whose disease has progressed on prior anthracyclines and taxanes. The safety profile of single-agent ixabepilone and combination ixabepilone plus capecitabine therapy is reviewed, outlining the steps to effectively manage and prevent common adverse events. Ixabepilone is generally well tolerated, and importantly, its toxicity profile does not overlap with that of capecitabine. Peripheral sensory neuropathy and neutropenia are the most common toxicities associated with ixabepilone; both can be effectively managed by monitoring patients and then, depending on severity, instituting a treatment delay until recovery and reducing the ixabepilone dose for subsequent treatment cycles. Ixabepilone dose reductions are recommended for most grade 3 events, excluding transient fatigue, arthralgia, and myalgia, whereas treatment discontinuation is recommended for persistent grade 3 neuropathy or any grade 4 nonhematological toxicity. Because ixabepilone exposure is greater in patients with hepatic impairment and those receiving concomitant strong cytochrome P-450 CYP3A4 inhibitors, dose adjustments and restrictions are recommended according to the degree of hepatic impairment, whether ixabepilone is administered alone or in combination with capecitabine, and whether a strong CYP3A4 inhibitor is being coadministered. Patients should be premedicated with oral H(1) and H(2) antihistamines to prevent hypersensitivity reactions. Unlike taxanes, corticosteroid premedication is not required unless a hypersensitivity reaction occurred during a previous cycle or during treatment with another Cremophor-containing agent. By effectively managing adverse events and taking steps to minimize them, clinicians can ensure that patients derive the maximum benefit from ixabepilone therapy.
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PMID:Proactive management of adverse events maintains the clinical benefit of ixabepilone. 1941 15

Postmenopausal patients with hormone-sensitive early breast cancer are typically treated with adjuvant endocrine therapy, which significantly reduces the risk of recurrence. Because treatment is of a long duration, side effects from adjuvant therapy can be problematic. The aromatase inhibitors (AIS) are replacing tamoxifen as first-line treatment agents for early breast cancer. Here, we present the side-effect data associated with AIS in relation to bone, gynecologic, and cardiovascular health and to arthralgia and myalgia. Although AIS have been shown to decrease bone density, increase arthralgia, and affect vaginal health, these adverse events are usually manageable, and several strategies can be followed to improve quality of life in women on AI treatment. To optimize adherence to therapy. It is important that these issues are addressed so that women can benefit from treatment.
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PMID:Safety of adjuvant endocrine therapies in hormone receptor-positive early breast cancer. 1967 17

The objective of the present study was to evaluate the effect of the switch of aromatase inhibitors (AIs) on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer. This was a 6-month, prospective, non-randomized, multicenter study. Patients who had discontinued anastrozole due to musculoskeletal symptoms were eligible to participate in this study, and received letrozole, which was initiated 1 month after anastrozole discontinuation. Musculoskeletal symptoms were systematically assessed for severity, location of the symptoms, presence of swelling and of morning stiffness by the oncologist patients when patients stopped taking their anastrozole, 1 month after the discontinuation of anastrozole, and 1, 3, and 6 months after initiating the letrozole therapy. The primary endpoint was the percentage of patients who discontinued letrozole due to the severe musculoskeletal symptoms. After switching from anastrozole therapy, and at the end of the 6-month letrozole treatment, 128 (71.5%) out of 179 patients (61.3 +/- 8.4 years) continued with letrozole. Fifty-one patients (28.5%) discontinued treatment due to severe joint pain. At the end of the 6-month, 116 patients (73.9%) had arthralgia, 33 (21.0%) myalgia, 25 (15.9%) arthritis, 22 (14.0%) tendinitis, and 20 (12.7%) polyalgic syndrome. Bivariate analysis of the factors associated with letrozole discontinuation showed that the duration of a prior anastrozole treatment was a significant predictor (P = 0.04). This study shows that in patients intolerant to one AI, switching to another agent allows a higher proportion of patients to continue the therapy and maximize hormonal adjuvant therapy and disease outcome benefits.
Breast Cancer Res Treat 2010 Feb
PMID:Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. 2003 81

The US oncology 9735 study showed the superior result of TC (docetaxel/cyclophosphamide) over AC (doxorubicin/cyclophosphamide), and now TC has been widely adopted for the treatment of early breast cancer. But in Japan there are few data on the safety and tolerability of this regimen. From January 2007 to April 2009, we treated 51 early breast cancer patients with TC in our hospital, and we summarized safety and tolerability profile, including hematologic toxicity and nonhematologic toxicity. Our patients experienced more febrile neutropenia (25.5%) compared with the original USO 9735 result (5%). This might be because we did not use prophylactic oral antibiotics. Skin toxicity was sometimes troublesome, including 3 cases (5.9%) of grade 3 skin rash. Toxicity assessment showed more asthenia, edema, neuropathy and myalgia, as is well known. Finally, we recommend prophylactic oral antibiotics, steroid premedication from the day before treatment and skin moisture, which may minimize the toxicity.
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PMID:[Safety and tolerability of docetaxel with cyclophosphamide for early breast cancer]. 2049 12

The safety and tolerance of docetaxel (especially 75 mg/m/2) plus cyclophosphamide (600 mg/m2) (TC therapy) as adjuvant chemotherapy for Japanese patients (n=47) with operable breast cancer was evaluated. Among 47 patients who received TC therapy, 38 patients (80.8%) were treated as scheduled for 4 courses every three weeks, and 6 patients (12.8%) were dose-reduced or the interval between courses was extended due to neutropenia or wound infection. Three patients (6.4%) quit TC therapy due to stomatitis or skin toxicities of grade 3. Although febrile neutropenia of grade 3 or 4 was observed in 2 patients (4.3%), TC therapy could be prescribed for these patients. Non-hematological side effects(such as edema, myalgia and arthralgia), occurred in relatively many cases, but were not remarkable. From these results, TC therapy (75/600 mg/m2) is considered to be a safe and tolerable regimen in Japanese patients operated for breast cancer.
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PMID:[Safety and tolerance of docetaxel (especially 75 mg/m2) with cyclophosphamide (TC therapy) as adjuvant chemotherapy for Japanese patients with operable breast cancer]. 2064 7


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