The different pharmacokinetic profiles of the intramuscularly administered antioestrogen fulvestrant and oral endocrine treatments have led to speculation among some physicians that this could result in a delayed time to response (TTR) with fulvestrant.

Docetaxel has to be considered as the reference control arm for second line chemotherapy for advanced NSCLC. Weekly docetaxel has been compared to standard 3-weekly schedule in a randomized fashion to determine if such schedule improves survival and quality of life. We performed a literature-based meta-analysis of all randomized clinical trials (RCTs) comparing weekly over 3-weekly docetaxel in advanced NSCLC.

To determine the overall survival and relative effect of multiple prognostic variables in cohorts of patients with advanced-stage ovarian cancer treated with platinum-based neoadjuvant chemotherapy in lieu of primary cytoreductive surgery.

The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of randomized controlled clinical studies, published between 1966 and 2004, the aim of which was the prevention of mucositis in cancer patients undergoing head and neck radiation, chemotherapy, or chemoradiation. The control group consisted of a placebo, no intervention, or another intervention group. Mucositis was scored by either the WHO, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) score, or the absence or presence of ulcerations, or the presence or absence of grades 3 and 4 mucositis. The meta-analyses included 45 studies fulfilling the inclusion criteria, in which 8 different interventions were evaluated: i.e., local application of chlorhexidine; iseganan; PTA (polymyxin E, tobramycine, and amphotericin B); granulocyte macrophage-colony-stimulating factor/granulocyte colony-stimulating factor (GM-CSF/G-CSF); oral cooling; sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G-CSF. Four interventions showed a significant preventive effect on the development or severity of oral mucositis: PTA with an odds ratio (OR) = 0.61 (95% confidence interval [CI], 0.39-0.96); GM-CSF, OR = 0.53 (CI: 0.33-0.87); oral cooling, OR = 0.3 (CI: 0.16-0.56); and amifostine, OR = 0.37 (CI: 0.15-0.89). To date, no single intervention completely prevents oral mucositis, so combined preventive therapy strategies seem to be required to ensure more successful outcomes.

Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.

To characterize the population pharmacokinetics of tipifarnib.

The risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk.

Capecitabine is a novel, orally administered fluoropyrimidine carbamate that has been approved for adjuvant treatment in patients with Stage III colon cancer, first-line metastatic colorectal cancer, and metastatic breast cancer, both as a single agent (for patients who are resistant to paclitaxel and anthracyclines) and in combination with docetaxel (after failure on anthracycline-based therapy). Capecitabine is being investigated in Phase I and II trials for the treatment of gastric, gastroesophageal, and esophageal cancers, primarily in the first-line metastatic setting but also in the adjuvant setting. The MEDLINE data base was searched for English-language clinical trials that were published from 1996 through October 2005 along with relevant abstracts that were presented at the American Society of Clinical Oncology and at meetings of the European Cancer Conference and the European Society of Medical Oncology. The most frequently investigated combinations were capecitabine with docetaxel, paclitaxel, cisplatin, or oxaliplatin, and capecitabine also has been combined with irinotecan. These therapies have yielded efficacy data that compare favorably with data from Phase III trials of parenteral 5-fluorouracil (5-FU) in the first-line metastatic setting, and they mostly are well tolerated. Capecitabine, when combined in doses <1250 mg/m(2) twice daily, consistently resulted in a lower frequency of Grade 3 or 4 toxic effects. Capecitabine, as a representative of oral fluoropymidine, is a promising agent in gastroesophageal cancers. Although some Phase III trials are completed, additional Phase III trials of capecitabine-based combinations that compare its efficacy and safety with parenteral 5-FU-based combinations, in both first-line metastatic and adjuvant settings, would be important.

The magnitude of the survival benefit of aromatase inhibitors (AIs) after 2-3 years of tamoxifen as adjuvant hormonal therapy for early breast cancer is still unclear. We performed a literature-based meta-analysis, to look how much advantages adjuvant the "early switch" strategy add over standard tamoxifen for 5 years.

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

The colony-stimulating factors (CSFs) are widely utilized to prevent neutropenic complications in both adults and children, but randomized controlled trials in the pediatric setting have reported varied results. A systematic review of the literature and meta-analysis were conducted to definitively assess the impact of prophylactic CSFs on the risk of febrile neutropenia (FN) in pediatric oncology patients.

There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms.

Treatment of cancer is increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers).

Oral and gastrointestinal (GI) mucositis are frequent complications of chemotherapy and radiotherapy for cancer, contributing to not only the morbidity of treatment but its cost as well. The risk associated with specific chemotherapeutic agents, alone and in combination, has been characterized previously. In the current study, we sought to estimate the risk associated with newer regimens for the treatment of non-Hodgkin's lymphoma (NHL) and common solid tumors.

High intake of soy foods has been proposed to contribute to the low breast cancer risk in Asian countries. However, results of epidemiologic studies of this association are highly variable, and experimental data suggest that soy constituents can be estrogenic and potentially risk enhancing. Thus, rigorous evaluation of available epidemiologic data is necessary before appropriate recommendations can be made, especially for women at high risk of breast cancer or those who have survived the disease.

Benefit and harm associated with treating actinic keratosis (AK) with the immune response modifier imiquimod was assessed using published randomized-controlled trials. Five randomized double-blind trials lasted 12-16 weeks and treated 1,293 patients. Complete clearance occurred in 50% of patients treated with imiquimod, compared to 5% treated with vehicle, and the number needed to treat (NNT) for one patient to have their keratosis completely cleared after 12-16 weeks was 2.2 (95% confidence interval 2.0-2.5). For partial (>/=75%) clearance the NNT was 1.8 (1.7-2.0). The proportion of patients with any adverse event, any local adverse event, or any treatment-related adverse event was substantially higher with imiquimod than with vehicle, and numbers needed to harm for one additional adverse event with imiquimod over 12-16 weeks ranged from 3.2 to 5.9. Particular local adverse events with imiquimod included erythema (27%), scabbing or crusting (21%), flaking (9%), erosion (6%), edema (4%), and weeping (3%). Imiquimod 5% cream was effective in the treatment of AK, preventing potential development of squamous cell carcinoma. Future investigation might be aimed at elucidating optimal dosing to minimize adverse events without detriment to efficacy, and evaluating long-term recurrence.

Despite several randomised trials comparing radiotherapy alone with concomitant radio-chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC), it is not clear whether the addition of chemotherapy improves survival.

To review the management of spontaneous ruptured hepatocellular carcinoma in the acute phase, the definitive treatment after hemostasis, and the prognosis.

A systematic review and meta-analysis was conducted to test the hypothesis that oncology health care workers are at an increased risk of cancer, reproductive complications and acute toxic events.

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36-40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.