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M Aapro

Publications and source records attributed to M Aapro.

At least 19 recordsLinked to original sources
PubMed2006

Effect of treatment with epoetin beta on short-term tumour progression and survival in anaemic patients with cancer: A meta-analysis.

To assess the early effect of epoetin beta on survival and tumour progression in anaemic patients with cancer, data were pooled from nine randomised clinical trials comparing epoetin beta with placebo or standard care. Studies were not primarily designed to assess these end points. Follow-up was for treatment duration plus 4 weeks following therapy completion. All adverse events (AEs) were retrospectively reviewed blinded, for progression. Thromboembolic events were also assessed. Data analysis involved standard statistical tests. Overall, 1413 patients were included (epoetin beta, n = 800; control, n = 613; 56% haematological, and 44% solid). Median initial epoetin beta dose was 30,000 IU/week. Overall survival during months 0-6 was similar with epoetin beta and control (0.31 vs 0.32 deaths/patient-year). No increased mortality risk was seen with epoetin beta (relative risk (RR) 0.97, 95% CI: 0.69, 1.36; P = 0.87). There was a significantly reduced risk of rapidly progressive disease for epoetin beta (RR 0.78, 95% CI: 0.62, 0.99; P = 0.042). Epoetin beta was associated with a slightly higher frequency of thromboembolic events vs control (5.9% vs 4.2% of patients) but thromboembolic-related mortality was identical in both groups (1.1%). Epoetin beta provided a slight beneficial effect on tumour progression and did not impact on early survival or thromboembolic-related mortality.

Adult↗
PubMed2006

Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases.

BACKGROUND: Bisphosphonates are recommended to prevent skeletal related events (SREs) in patients with breast cancer and bone metastases (BCBM). However, their clinical and economic profiles vary from one agent to the other. MATERIALS AND METHODS: Using modeling techniques, we simulated from the perspective of the UK's National Health Service (NHS) the cost and quality adjusted survival (QALY) associated with five commonly-used bisphosphonates or no therapy in this patient population. The simulation followed patients into several health states (i.e. alive or dead, experiencing an SRE or no SRE, and receiving first or second line therapy). Drugs costs, infusion costs, SREs costs, and utility values were estimated from published sources. Utilities were applied to time with and without SREs to capture the impact on quality of life. RESULTS: Compared to no therapy, all bisphosphonates are either cost saving or highly cost-effective (with a cost per QALY < or = 6126 pounds sterlings). Within this evaluation, zoledronic acid was more effective and less expensive than all other options. CONCLUSIONS: Based on our model, the use of bisphosphonates in breast cancer patients with bone metastases should lead to improved patient outcomes and cost savings to the NHS and possibly other similar entities.

Bone Diseases↗
PubMed2006

Improving bone health in patients with early breast cancer by adding bisphosphonates to letrozole: the Z-ZO-E-ZO-FAST program.

Women undergoing treatment for breast cancer often have a number of pre-existing risk factors for bone loss, including existing or induced postmenopausal status. Long-term anticancer treatments may further augment this risk, inducing further bone-loss, increasing the incidence of bone fractures, associated morbidity and mortality, and healthcare costs. Long-term treatment with third-generation antiaromatase agents (AAAs) is used more and more instead of or after the selective estrogen-receptor modulator tamoxifen for the adjuvant treatment of postmenopausal women with breast cancer. These AAAs include anastrozole, letrozole, and exemestane, and all are superior to tamoxifen in both efficacy and safety. In particular, they reduce the incidence of serious adverse events such as thromboembolism and endometrial cancer that are associated with tamoxifen treatment. On the other hand, the AAAs lead to profound estrogen depletion and appear to have a pronounced effect on bone mineral density (BMD), and a significantly higher incidence of osteoporosis/osteopenia and bone fracture has been reported in some trials. Bisphosphonate therapies, including zoledronic acid (ZA), have emerged as a promising means of reducing bone loss associated with antiaromatase therapy. Several large, randomized, multicenter trials are underway to determine whether upfront or delayed ZA therapy can decrease BMD losses in patients undergoing treatment with the antiaromatase agent letrozole (Z-FAST; ZO-FAST, and E-ZO-FAST), and early results from the Zometa-Femara adjuvant synergy trial (Z-FAST) trial indicate a significant benefit of upfront ZA therapy compared with delayed ZA therapy. Forthcoming results from all these trials should determine whether ZA could be used to improve bone heath in women undergoing adjuvant therapy with AAAs for breast cancer.

Aromatase Inhibitors↗
PubMed2005

Incidence of febrile neutropenia and neutropenic infections in elderly patients receiving anthracycline-based chemotherapy for breast cancer without primary prophylaxis with colony-stimulating factors.

There is concern about the potential increase of hematological toxicity in elderly patients treated with chemotherapy. Recently, primary prophylaxis with colony-stimulating factors (CSFs) was proposed for elderly patients receiving moderately toxic chemotherapy. However, evidence for the benefits of this primary prophylaxis for elderly breast cancer patients is currently lacking. We retrospectively analyzed the incidence of febrile neutropenia (FN) and neutropenic infections in elderly breast cancer patients receiving anthracycline-based chemotherapy without primary prophylaxis with colony-stimulating factors. In addition, we assessed the direct costs of hospitalization for these complications. Febrile neutropenia or neutropenic infection occurred in 13% of the 46 patients. Further studies are needed to adequately evaluate the risk of neutropenic complications (NC) in elderly patients receiving standard-dose chemotherapy for breast cancer and the potential benefits of primary prophylaxis with colony-stimulating factors.

Aged↗
PubMed2004

Treatment implications for radiation-induced nausea and vomiting in specific patient groups.

Radiation-induced nausea and vomiting (RINV) affect the management and quality of life of cancer patients. Current guidelines for RINV prevention recommend prophylaxis with a 5-hydroxytryptamine (5-HT(3))-receptor antagonist for patients receiving moderately or highly emetogenic radiotherapy regimens. Randomised trials have compared such antagonists with conventional antiemetics, and have demonstrated their efficacy and safety. Special consideration is needed for antiemetic treatment in certain patient groups, particularly the elderly and those with renal or hepatic impairment. Radiation oncologists should be aware of the effect on antiemetic treatment of factors such as comorbid conditions (particularly cardiovascular disease), polypharmacy and drug-drug interactions, and choose the agent with the lowest potential for additional complications. The most appropriate antiemetic treatment to improve patient compliance and quality of life should ideally combine proven efficacy with uncomplicated administration and convenient dosing regimens.

Age Factors↗
PubMed2004

HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.

Adolescent↗
PubMed2004

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.

Aged↗
PubMed2003

Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists.

Advances in antiemetic therapy for chemotherapy-induced emesis have resulted in improved protection against symptoms occurring within 24 h of chemotherapy. However, the vomiting which tends to occur beyond 24 h after chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of chemotherapy-induced emesis includes a serotonin (5-HT(3)) antagonist and a corticosteroid. The neurokinin-1 (NK(1)) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT(3) antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK(1) antagonist had a superior prevention of emesis. However, in the first 24 h after cisplatin, emesis occurred in fewer patients who received the 5-HT(3) antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK(1) antagonist occurred within the first 8-12 h of chemotherapy, whereas the treatment failures in patients who received a 5-HT(3) antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in chemotherapy-induced vomiting. Serotonin mediates the early vomiting process that occurs within 8-12 h following cisplatin-based chemotherapy, after which time substance P acting at NK(1) receptors becomes the dominant mediator of vomiting

Antiemetics↗
PubMed2003

Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.

BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)] during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (</=5 days post-chemotherapy) and overall tolerability. RESULTS: 563 patients were evaluable for efficacy. CR rates were significantly higher (P <0.01) for palonosetron 0.25 mg than ondansetron during the acute (0-24 h) (81.0% versus 68.6%, respectively), delayed (24-120 h) (74.1% versus 55.1%) and overall (0-120 h) (69.3% versus 50.3%) periods. CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals. Both treatments were well tolerated. CONCLUSIONS: A single i.v. dose of palonosetron 0.25 mg was significantly superior to i.v. ondansetron 32 mg in the prevention of acute and delayed CINV.

Adult↗
PubMed2003

Rapid intravenous administration of granisetron prior to chemotherapy is not arythmogenic: results of a pilot study.

Patients with advanced malignancy are at an increased risk of cardiac arrhythmias, from their cancer and cardiotoxic treatments. Supportive care products co-administered should therefore not increase this risk. No clinically important cardiovascular effects are associated with the administration of granisetron over 30 s. To determine the effects of a rapid (1 s) injection of granisetron, 3 mg, on measures of cardiac repolarisation, a pilot study was performed in 17 patients undergoing moderately/highly emetogenic chemotherapy at two centres. All received dexamethasone, 8-12 mg, infused over 30 min, followed immediately by granisetron and then chemotherapy. Twelve-lead electrocardiograms (ECGs) performed before granisetron treatment, 2 h later and the following day (11 patients) showed no differences in QTc(end max), QTc(apex max) or QT-interval dispersion between baseline and subsequent measurements, and there were no significant secondary adverse events. On this basis, granisetron should be considered the first-choice antiemetic for patients at increased risk of cardiac complications.

Adult↗
PubMed2001

Pharmacology.

Explore the source record for details and available documents.

Aged↗
PubMed2001

Chemotherapy in elderly patients with colorectal cancer.

BACKGROUND: Colorectal cancer is usually diagnosed in patients around 70 years of age. With a continuous increase in life expectancy we may expect a higher number of elderly patients in the future. Because patients above 70 or 75 years are often excluded there is uncertainty as to what extent systemic adjuvant and palliative treatment should be offered to elderly patients. METHODS: We reviewed the available literature on adjuvant and metastatic colorectal cancer in order to identify reports on elderly patients treated within chemotherapy trials. RESULTS: Only about 20% of patients entering clinical trials belong to the age group of over 70 years and represent the minority of the very fit patients. Compared to their younger counterparts 5-FU-based treatment appears to be equally effective and more toxic according to some reports. Data regarding raltitrexed, oral fluoropyrimidines, topoisomerase I inhibitors or DACH-platin derivates are limited but suggest no age-specific differences in activity or toxicity. CONCLUSIONS: Elderly patients should not be excluded from clinical trials and studies in unfit elderly patients are warranted. Elderly patients need more attention regarding their functional, social and mental status. Fit elderly patients should be offered adjuvant or palliative chemotherapy.

Aged↗
PubMed2000

Assessment of the older cancer patient.

The correct assessment of a cancer patient is a key step in the treatment process. In older people, this assessment entails not only the patient's basic medical history and the standard cancer staging, but also much more comprehensive evaluation of the various facets of the patient's health and environment that may interfere with his or her therapy. Patient fitness for elective surgery, radiation therapy, and chemotherapy must be considered. Geriatricians have defined the relevant aspects of the general evaluation of the older person, and now this work is being adapted to cancer patients. This article reviews the various aspects of a comprehensive assessment applicable to the cancer patient in settings such as academic oncology programs, cooperative group studies, and private oncology practice.

Aged↗
PubMed2000

New directions in the treatment of colorectal cancer: a look to the future.

Today, adjuvant 5-fluorouracil based therapy is known to significantly reduce the relapse rates and the risks of dying from resected colon cancer; chemotherapy approximately doubles overall survival of advanced colorectal cancer and second line treatment prolongs the survival of patients compared with best supportive care. At the molecular level a number of key genes are often mutated in cancer of the colon and some of these key regulators of apoptosis are discussed (p53 and bcl-2 family of proteins). Dihydropyrimidine dehydrogenase (DPD) activity may be a potential factor controlling fluorouracil (FU) responsiveness at the tumoral level and its importance is stressed. The rationale of combining FU with DPD inhibitors is fairly strong. Ethynyluracil, UFT and S1 pursue this strategy while capecitabine has another the rationale. Drug resistance should be at least partially overcome by combination chemotherapy (FU plus mitomycin, oxaliplatin, irinotecan) and combined modality (FU+RT) regimens. Improved surgical techniques and radiotherapy have substantially decreased local failure rates for rectal cancers. Finally, innovative treatment modalities such as anti-angiogenetic and antimetastatic agents, farnesyl transferase inhibitors, vaccine and gene therapy are in early clinical trials.

Antimetabolites, Antineoplastic↗