Laura Boehnke Michaud

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (27)113.28 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: Background: Trastuzumab has become a mainstay of therapy for human epidermal growth factor receptor-2 overexpressed breast cancer in nearly all stages of the disease. Like many monoclonal antibodies, trastuzumab is associated with infusion-related reactions (IRRs) that are not well described, and incidence varies widely between reports (0.7%-40% of patients). Materials and methods: A retrospective chart review of breast cancer patients who received trastuzumab was conducted. The primary objective was to describe the incidence, risk factors, and management of IRRs during the first 12 weeks of trastuzumab therapy in a general population of breast cancer patients. Results: A total of 197 patients who received trastuzumab (1,788 doses) were evaluated. Thirty-three IRRs were identified in 32 patients, resulting in an incidence of 16.2% of patients and 1.8% of doses. All IRRs were mild or moderate in severity and were successfully managed with supportive medications and/or by temporarily stopping the infusion. All patients received subsequent cycles of trastuzumab, with only one patient experiencing a subsequent reaction. Body mass index, stage of disease, and use of premedications were significantly associated with IRRs by multivariate logistic regression analysis. Conclusion: Overall, these results support that the vast majority of IRRs occur with the first infusion, are mild in severity, and are easily managed. In addition, risk factors were identified that may help to identify a population of patients at increased risk of IRRs who may benefit from premedication.
    Preview · Article · Feb 2014 · The Oncologist
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    [Show abstract] [Hide abstract] ABSTRACT: Background:Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. METHODS: Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. RESULTS: Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. CONCLUSIONS: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.
    Preview · Article · May 2013 · Journal of Oncology Pharmacy Practice
  • Article: Antiemesis
    [Show abstract] [Hide abstract] ABSTRACT: Chemotherapy-induced nausea and vomiting (emesis) can significantly affect a patient's quality of life, leading to poor adherence with further chemotherapy treatment. In addition, nausea and vomiting can result in other serious complications and deterioration of the patient's status. These guidelines explore the prevention, treatment, and management of various types of emesis experienced by cancer patients, such as breakthrough, radiation-induced, and anticipatory. The latest 2009 NCCN Guidelines include updated dosing recommendations for palonosetron and dexamethasone and the inclusion of the granisetron transdermal patch after FDA approval.
    No preview · Article · Apr 2012 · Journal of the National Comprehensive Cancer Network: JNCCN
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    [Show abstract] [Hide abstract] ABSTRACT: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. The authors performed CYP2D6 genotyping from whole blood and fresh frozen tumor samples (n 106) in patients at The University of Texas MD Anderson Cancer Center who were receiving, or had received, tamoxifen as adjuvant therapy for early breast cancer (EBC), using the AmpliChip CYP450 Test. Each patient's medical history was assessed for drugs that affected CYP2D6. Fifty-five patients who had experienced breast cancer recurrence were matched (by date of diagnosis, menopausal status, clinical stage [TNM Staging System], and race) to patients without recurrence. Unadjusted for other patient characteristics, the odds ratio for disease recurrence associated with CYP2D6 functional status was 1.0 (95% confidence interval, 0.35-2.85). After adjustment for stage, CYP2D6 inhibitors (moderate or strong vs none), and follow-up time, no significant association was found between CYP2D6 genotype and breast cancer recurrence in patients who were treated with adjuvant tamoxifen for EBC. This case-control study demonstrated no significant effect of CYP2D6 genotype on risk of recurrence in breast cancer patients who received adjuvant tamoxifen therapy.
    Preview · Article · Mar 2012 · Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: To determine the effect of formal medication therapy management (MTM) services on pharmacist workload, as well as to describe the population receiving MTM, describe the services provided, and determine the reimbursement rate for billed MTM services. MTM Current Procedural Terminology (CPT) code claims, electronic medical records, and pharmacist MTM logs. A retrospective review of all MTM charges from January 1, 2010, to March 31, 2010, was performed. Data collected included location of the MTM visit, age, gender, insurance, primary malignancy, comorbidities, home medications, time to complete and document the MTM visit, and rate of reimbursement. In the 3-month period, 239 MTM visits were completed. It took pharmacists a median of 20 minutes (range 15-127) of face-to-face time and 18 minutes (5-90) for documentation per visit. To date, no claims for MTM have been rejected, and reimbursement rates range from 47% to 79% depending on the insurance provider. MTM in the ambulatory clinic is feasible despite the increase in pharmacist workload from documenting and billing. The increased visibility of clinical pharmacy services justifies the extra time required for formal MTM.
    No preview · Article · Mar 2012 · Journal of the American Pharmacists Association
  • [Show abstract] [Hide abstract] ABSTRACT: Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS). Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005. The median time followed by the AMS was 151 days. Fifty three percent (n = 1651) of total lab draws (n = 3129) were within the target therapeutic INR range 2-3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma). To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.
    No preview · Article · Mar 2011 · Journal of Oncology Pharmacy Practice
  • Laura Boehnke Michaud
    [Show abstract] [Hide abstract] ABSTRACT: To discuss trends in breast and prostate cancer prevalence and survival; risk factors for bone loss, osteoporosis, and fractures and the approach to risk assessment in patients with these malignancies; established and investigational drug therapies for managing cancer treatment-induced bone loss and osteoporosis; and the role of health-system pharmacists in promoting bone health in patients with breast or prostate cancer. Breast cancer and prostate cancer are common, deadly diseases, but many survivors are alive today because of improvements in early detection and treatment over the past 10-15 years. Cancer chemotherapy, corticosteroids, hormone-ablation therapy, and other common risk factors place patients with breast or prostate cancer at high risk for bone loss, osteoporosis, and fractures. Most patients with breast or prostate cancer should undergo assessment of risk for bone loss and osteoporosis that involves a bone-related history and physical examination, dual-energy X-ray absorptiometry scanning, and the FRAX fracture risk assessment tool from the World Health Organization. A recent National Comprehensive Cancer Network task force report on bone health in cancer care provides recommendations for considering the use of pharmacologic therapy on the basis of the results of this assessment. Bisphosphonates are useful for slowing or preventing bone loss associated with hormone-ablation therapy in women with breast cancer and men with prostate cancer, although fracture data are limited in women and not available in men. The usefulness of other therapies (selective estrogen receptor modulators, teriparatide, calcitonin salmon, and estrogens) is limited by adverse effects, a lack of experience with the drugs in these patient populations, or both. Various drug therapies are in development for managing cancer treatment-induced bone loss and osteoporosis. The agent closest to approval by the Food and Drug Administration, denosumab, has been shown to improve bone mineral density in women and men receiving hormone-ablation therapy for breast or prostate cancer, but additional data are needed to dispel safety concerns that could limit the use of this drug in these patient populations. Health-system pharmacists play an important role in screening patients with a history of breast or prostate cancer for bone loss or osteoporosis, making drug therapy recommendations to address the problem, and counseling patients on modifiable risk factors for osteoporosis and proper use of drug therapies to improve bone health. Health-system pharmacists can improve the detection and management of cancer treatment-induced bone loss and osteoporosis in patients receiving systemic therapy for breast or prostate cancer.
    No preview · Article · Apr 2010 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
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    Laura Boehnke Michaud
    [Show abstract] [Hide abstract] ABSTRACT: To review the pharmacologic properties of a novel class of chemotherapeutic agents, the epothilones, and to summarize findings from recent clinical trials investigating the various epothilones in cancer therapy. Literature searches were conducted using MEDLINE, PubMed, and the abstract search engines for the American Society of Clinical Oncology and American Association for Cancer Research annual meetings (all searches through November 2008). Primary search terms included epothilone, BMS-247550, ixabepilone, EPO906, patupilone, sagopilone, and ZK-EPO. Publications were given priority for inclusion if they discussed structural or pharmacologic properties of the epothilones as a class or if they included preclinical or clinical data for epothilones currently in clinical development. The epothilones are a novel class of microtubule-stabilizing agents (MSAs). Epothilones are structurally and pharmacologically distinct from taxanes, but the exact ways in which the pharmacophores of the 2 classes differ has not been firmly established. A number of natural, semisynthetic, and fully synthetic epothilones are in various stages of clinical development. These agents differ from each other and from existing MSAs; these differences influence potency, stability, and solubility. Ixabepilone is currently approved to treat multidrug-resistant metastatic breast cancer and has demonstrated efficacy in earlier stages of breast cancer and in several other tumor types. Patupilone and sagopilone are currently under clinical investigation and have each shown promise in a number of treatment settings and tumor types. All 3 agents appear to be associated with manageable toxicities, but no class-wide toxicity profile exists for the epothilones and dose-limiting toxicities differ among the agents. The epothilones have demonstrated significant potential for addressing the growing therapeutic challenge of taxane resistance, and the ever-increasing pool of information regarding structure-activity relationships of these MSAs will help to optimize microtubule-targeted chemotherapy.
    Preview · Article · Aug 2009 · Annals of Pharmacotherapy
  • [Show abstract] [Hide abstract] ABSTRACT: Neutropenia and resulting febrile neutropenia (FN) can be induced by myelosuppressive chemotherapy. FN is a major dose-limiting toxicity of chemotherapy, often requiring hospitalization to evaluate and treat. Further, these complications often result in dose reductions or treatment delays, which may compromise clinical outcomes. Although the prophylactic use of colony-stimulating factors (CSFs) can reduce the risk, severity, and duration of FN, they are not administered to all patients undergoing myelosuppressive chemotherapy because of the associated costs. Selective use, however, may enhance cost-effectiveness by directing treatment toward patients most likely to benefit. Filgrastim and pegfilgrastim, both granulocyte colony-stimulating factors (G-CSF), have FDA approval for use in the prevention of chemotherapy-induced neutropenia. In contrast, the labeled indication for sargramostim, a granulocyte-macrophage colony-stimulating factor (GM-CSF), is limited to use after induction therapy for acute myeloid leukemia and in various stem cell transplantation settings. These guidelines focus on the use of CSFs in the cancer setting; specifically addressing adult patients with solid tumors and nonmyeloid malignancies.
    No preview · Article · Feb 2009 · Journal of the National Comprehensive Cancer Network: JNCCN
  • Laura Boehnke Michaud
    [Show abstract] [Hide abstract] ABSTRACT: The epothilones are a new class of microtubule-stabilizing drugs that exert potent antitumor activity against taxane-resistant and multidrug resistant cell lines. The most clinically advanced member of this class is the semisynthetic epothilone B derivative ixabepilone. This article reviews the preclinical and clinical data on ixabepilone in patients with locally advanced and metastatic breast cancer (MBC) and provides guidance for pharmacists on its optimal use. PubMed and conference proceedings through August 2008. In preclinical studies, ixabepilone has demonstrated potent antitumor activity and low susceptibility to mechanisms that confer tumor resistance. Clinically meaningful benefits have been achieved with ixabepilone monotherapy in phase 2 trials of patients with MBC who have failed previous chemotherapies (anthracyclines, taxanes, or capecitabine). In a randomized, phase 3 trial, the combination of ixabepilone and capecitabine proved more effective than capecitabine alone after the failure of taxane and anthracycline regimens. At the recommended dose and schedule, the therapeutic ratio of ixabepilone is generally favorable, and its adverse effects (notably neutropenia and peripheral neuropathy) are generally manageable and reversible. Ixabepilone represents an advance in the treatment of anthracycline - and taxane-pretreated MBC. Future studies will define its efficacy in combination with other drugs used in the treatment of MBC, as well as in other types of cancer.
    No preview · Article · Feb 2009 · Journal of Oncology Pharmacy Practice
  • Laura Boehnke Michaud
    [Show abstract] [Hide abstract] ABSTRACT: Breast cancer, the second leading cause of cancer mortality among women in the U.S., following lung cancer is described and the number of treatment options for patients with breast cancer, which has been accompanied by a trend toward declining cancer mortality, is reviewed. Despite these advances in cancer therapy, many patients with early stage breast cancer eventually progress to metastatic disease. Several prognostic factors have been identified for patients with metastatic breast cancer, including tumor volume and location, comorbid conditions, response to prior therapy, and the presence of molecular tumor markers (e.g., estrogen receptors [ER] and human epidermal growth factor receptor 2 [HER2]). Metastatic breast cancer is usually incurable, and the goals of therapy are palliation of symptoms, extending survival, and improving quality of life. Options for the medical management of metastatic breast cancer include endocrine therapy, cytotoxic chemotherapy, and targeted biologic agents. Treatment guidelines developed by the National Comprehensive Cancer Network generally recommend endocrine therapy for patients with ER-positive or progesterone receptor (PR)-positive disease, for patients with bone or soft tissue metastasis, or those with asymptomatic visceral disease. Cytotoxic chemotherapy alone is usually recommended for patients with ER-negative/PR-negative disease, who have symptomatic visceral disease, or whose tumors are HER2-negative or rapidly growing. Biologic agents (e.g., trastuzumab and lapatinib) alone or in combination are recommended for patients with HER2-positive disease. Treatment options for meta-static breast cancer continue to increase as new antitumor medications enter clinical practice and controlled clinical trials evaluate the optimal combinations of established and novel medications.
    No preview · Article · Jun 2008 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
  • Laura Boehnke Michaud · Julie Phillips Karpinski · Kellie L Jones · Janet Espirito
    [Show abstract] [Hide abstract] ABSTRACT: The risks and key concepts regarding the use of dietary supplements in patients with cancer are described. There are six common characteristics of dietary supplements that must be addressed when used by patients with cancer. Clinicians must establish if the supplement is an antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or immunomodulating properties, has hormonal properties, has known safety issues, and has known or theoretical drug interactions. These six characteristics of the dietary supplements commonly used by patients with cancer are reviewed to aid in the analysis of the scientific data and communication of the results with the patient or family members. A framework upon which clinicians can adequately help patients make informed decisions regarding the use of complimentary and alternative medicine and dietary supplements is also described. When evaluating the appropriateness of a supplement for use by a patient with cancer, clinicians must conduct a safety review (evaluate the six characteristics). If the supplement is considered safe, an efficacy review must be conducted, after which the clinicians can recommend the supplement's use, accept the patient's decision to use the supplement if no or inconclusive evidence exists, or discourage use if there is conclusive evidence supporting inefficacy. Available resources for locating information regarding dietary supplements are also discussed. Counseling patients with cancer about dietary supplements requires a systematic thought process that considers the available theories and data, as well as the patients' views about the agents.
    No preview · Article · Apr 2007 · American Journal of Health-System Pharmacy
  • Laura Boehnke Michaud · Julie Phillips Karpinski · Kellie L Jones · Janet Espirito
    [Show abstract] [Hide abstract] ABSTRACT: The risks and key concepts regarding the use of dietary supplements in patients with cancer are described. There are six common characteristics of dietary supplements that must be addressed when used by patients with cancer. Clinicians must establish if the supplement is an antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or immunomodulating properties, has hormonal properties, has known safety issues, and has known or theoretical drug interactions. These six characteristics of the dietary supplements commonly used by patients with cancer are reviewed to aid in the analysis of the scientific data and communication of the results with the patient or family members. A framework upon which clinicians can adequately help patients make informed decisions regarding the use of complimentary and alternative medicine and dietary supplements is also described. When evaluating the appropriateness of a supplement for use by a patient with cancer, clinicians must conduct a safety review (evaluate the six characteristics). If the supplement is considered safe, an efficacy review must be conducted, after which the clinicians can recommend the supplement's use, accept the patient's decision to use the supplement if no or inconclusive evidence exists, or discourage use if there is conclusive evidence supporting inefficacy. Available resources for locating information regarding dietary supplements are also discussed. Counseling patients with cancer about dietary supplements requires a systematic thought process that considers the available theories and data, as well as the patients' views about the agents.
    No preview · Article · Mar 2007 · American Journal of Health-System Pharmacy
  • [Show abstract] [Hide abstract] ABSTRACT: Chemotherapy-induced neutropenia can cause complications that result in dose reductions or treatment delays that can, in turn, compromise clinical outcomes. Although the prophylactic use of colony-stimulating factors (CSFs) can reduce the risk, severity, and duration of severe and febrile neutropenia, they are not routinely administered to all patients undergoing myelosuppressive chemotherapy because of the costs. Selective use may, however, enhance their cost-effectiveness. These guidelines discuss the preventative or prophylactic use of recombinant human granulocyte-CSF to reduce the incidence, length, and severity of chemotherapy-related neutropenia and and prevent life-threatening complications.
    No preview · Article · Mar 2007 · Journal of the National Comprehensive Cancer Network: JNCCN
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    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX). Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF). The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up. The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.
    Full-text · Article · Oct 2006 · Journal of Clinical Oncology
  • Laura Boehnke Michaud · Susan Goodin
    [Show abstract] [Hide abstract] ABSTRACT: The pathophysiology, frequency, sequelae, diagnosis, and treatment of cancer-treatment-induced bone loss (CTIBL) are discussed. CTIBL is a long-term complication associated with cancer therapies that can directly or indirectly affect bone metabolism. Although CTIBL can occur in any patient receiving a cancer therapy known to cause bone loss, CTIBL is most common in patients with breast or prostate cancer who receive chemotherapy, hormone therapy, or surgical castration, as these can cause hypogonadism and induce bone loss. CTIBL causes bone fragility and an increased susceptibility to fractures; therefore, prevention, early diagnosis, and treatment of CTIBL are essential to decrease the risk of fracture. Bone loss occurs more rapidly and tends to be more severe in patients with CTIBL compared with those with normal age-related bone loss. Fractures of the hip, vertebra, and wrist are the fractures most commonly associated with bone loss. CTIBL is diagnosed by measuring bone mass using bone densitometry. Treatment of CTIBL consists of changing diet and lifestyle such as optimizing calcium and vitamin D intake, exercising, modifying behaviors known to increase the risk of CTIBL and pharmacologic therapy with hormone replacement therapy (HRT), selective estrogen-receptor modifiers (SERMs), calcitonin, or a bisphosphonate. Early identification and treatment of CTIBL are essential to prevent fractures. Patients should be instructed to optimize calcium and vitamin D intake, exercise regularly, and modify lifestyle behaviors known to cause bone loss. Patients with CTIBL should be treated with an oral or i.v. bisphosphonate; SERMs or HRT may be an option in some patients if contraindications do not exist.
    No preview · Article · Apr 2006 · American Journal of Health-System Pharmacy
  • Laura Boehnke Michaud · Susan Goodin
    [Show abstract] [Hide abstract] ABSTRACT: The pathophysiology, frequency, sequelae, diagnosis, and treatment of cancer-treatment-induced bone loss (CTIBL) are discussed. CTIBL is a long-term complication associated with cancer therapies that can directly or indirectly affect bone metabolism. Although CTIBL can occur in any patient receiving a cancer therapy known to cause bone loss, CTIBL is most common in patients with breast or prostate cancer who receive chemotherapy, hormone therapy, or surgical castration, as these can cause hypogonadism and induce bone loss. CTIBL causes bone fragility and an increased susceptibility to fractures; therefore, prevention, early diagnosis, and treatment of CTIBL are essential to decrease the risk of fracture. Bone loss occurs more rapidly and tends to be more severe in patients with CTIBL compared with those with normal age-related bone loss. Fractures of the hip, vertebra, and wrist are the fractures most commonly associated with bone loss. CTIBL is diagnosed by measuring bone mass using bone densitometry. Treatment of CTIBL consists of changing diet and lifestyle such as optimizing calcium and vitamin D intake, exercising, modifying behaviors known to increase the risk of CTIBL and pharmacologic therapy with hormone replacement therapy (HRT), selective estrogen-receptor modifiers (SERMs), calcitonin, or a bisphosphonate. Early identification and treatment of CTIBL are essential to prevent fractures. Patients should be instructed to optimize calcium and vitamin D intake, exercise regularly, and modify lifestyle behaviors known to cause bone loss. Patients with CTIBL should be treated with an oral or i.v. bisphosphonate; SERMs or HRT may be an option in some patients if contraindications do not exist.
    No preview · Article · Apr 2006 · American Journal of Health-System Pharmacy
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    [Show abstract] [Hide abstract] ABSTRACT: Capecitabine is active against anthracycline- and taxane-pretreated metastatic breast cancer. Post-marketing use of capecitabine at the FDA-approved dose (2500 mg/m2/day) leads to unacceptable toxicity in many patients. Dose reductions anecdotally improve tolerability without compromising efficacy. This retrospective analysis was designed to verify these anecdotal reports. Patients and methods: We retrospectively reviewed the records of 141 consecutive patients with metastatic breast cancer identified from pharmacy records as receiving capecitabine outside of a clinical trial between May 1998 and February 1999. Responses were defined as clinical improvement (ID), stabilization of disease (SD) for 6 weeks or longer, or progression (PD). Patients were grouped according to the starting dose level of capecitabine: A=2500+/-5% (dose range 2385-2560) mg/m2/day; B=2250+/-5% (range 2130-2350) mg/m2/day; C < or = 2000+5% (range 1000-2100) mg/m2/day. We also reviewed the safety profile of capecitabine at these doses and performed a safety review of capecitabine in phase II and III metastatic breast and colorectal cancer trials. Clinical data were available for 113 patients (105 for response, 106 for toxicity). The median age was 52.5 years and the mean number of prior metastatic chemotherapy regimens was 2 (range 0-7). The mean capecitabine starting dose was 2220 mg/m2/day and the median number of cycles administered was 4 (range 1-19). The mean tolerated dose was 2040 mg/m2/day (range 960-2670). Grade 3/4 toxic effects at dose levels A, B and C, respectively, included palmar-plantar erythrodysesthesia (33%, 63%, 20%), diarrhea (13%, 12%, 3%), stomatitis (8%, 0%, 3%), and nausea/vomiting (4%, 6%, 5%). Forty per cent of all patients required capecitabine dose reductions; fewer patients treated with 2000 mg/m2/day required dose modification (28%). Five per cent of the patients required discontinuation of capecitabine owing to toxicity. Patients started at the lowest doses of capecitabine did not have poorer response rates or shorter time to progression. This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.
    Preview · Article · Sep 2005 · Annals of Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Chemotherapy-induced neutropenia is the major dose-limiting toxicity of systemic cancer chemotherapy, associated with substantial morbidity, mortality, and cost. Although prophylactic colony-stimulating factors (CSFs), can reduce this complication, their routine use in all patients on myelosuppressive chemotherapy is prohibitively costly. Selective use in patients most at risk for neutropenia may enhance cost-effectiveness, but determining the actual risk is complicated by issues in reporting myelosuppression and dose intensity, among other factors. For this reason, NCCN experts developed these guidelines to assist practitioners in the appropriate prophylactic use of CSFs.
    No preview · Article · Aug 2005 · Journal of the National Comprehensive Cancer Network: JNCCN
  • No preview · Conference Paper · Jun 2005