Interferon-alpha (IFN-alpha) has been extensively explored for its efficacy in various disease conditions and is currently used as a standard treatment in several of these. Its use is accompanied by a wide variety of possible side effects. These side-effects may hamper reaching and maintaining the dose needed for maximal therapeutic effect while their occurrence can outweigh clinical benefit of IFN-alpha treatment. This review addresses the toxicity profile of IFN-alpha, the presumed pathophysiology of the different side effects and the strategies to handle these.

Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.

Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking.

Advanced, metastatic non-small-cell lung cancer (NSCLC) remains a challenge to oncologists. There is little doubt that platinum-based combination chemotherapy improves survival and has a palliative effect by improved patients' symptoms and quality of life. Yet chemotherapy is not curative, is associated with toxicity, and can be costly. In most recent phase III trials, the median survival time is 8 to 10 months. Therefore, the optimal duration of therapy-one that balances survival and palliative effects against toxicity, cost, and intrusiveness on patients' lives-remains an important issue. Three recent randomized trials that addressed this in stage IIIB/IV NSCLC are reviewed. Two evaluated brief durations of first-line therapy (3 cycles in one, 4 in the other) versus longer-duration therapy (6 cycles and continuous therapy, respectively). No benefit in response rate, symptom relief, quality of life, or survival was noted for the longer-duration therapy. In addition, cumulative toxicities occurred more frequently in patients who received longer treatment durations. The third trial administered 4 cycles of first-line platinum-based therapy and then randomized responding patients to observation or 6 months of further therapy with vinorelbine. No survival benefit was noted for vinorelbine. There trials suggest that duration of first-line therapy in advanced, metastatic NSCLC should be brief (3 to 4 cycles). Prolonged therapy does not appear to improve survival and carries the risk of cumulative toxicity. Second-line therapy considered in those patients fit enough to receive it at the time of disease progression.

To review the clinical evidence for routine use of bleomycin test dosing.

Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function.

Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.

Treatment with epoetin alfa has repeatedly been shown to improve the quality of life (QoL) of cancer patients with anaemia. We used meta-analytical techniques to synthesise data from all available (published and unpublished) studies of epoetin alfa in cancer patients receiving chemotherapy that used validated QoL instruments. Results from 23 studies were synthesised. These employed the CLAS, FACT, SF-36 and ECOG (WHO) QoL scales. The meta-analysis indicated that treatment with epoetin alfa was associated with a clear and statistically significant improvement in QoL as measured by all subscales of CLAS, all subscales of FACT, and 5 subscales of SF-36. In contrast, control groups experienced no significant change, or, in some cases, a deterioration in QoL. Improvement was related to treatment duration. The generic ECOG (WHO) performance scale indicated that, even though epoetin alfa treatment is associated with clear benefits in terms of QoL, this population of patients receiving chemotherapy for cancer experience a gradual decrease in functional status over time.

Bacterial infections are a major cause of illness and death in patients who are neutropenic after chemotherapy treatment for cancer. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections but not in reducing mortality rates.

Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN.

In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.

Aromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.

The antiemetic efficacy and tolerability of Tropisetron (Navoban, Novartis Pharma Switzerland AG, Bern), a selective 5-hydroxytriptamine receptor antagonist, has been assessed in the prevention of acute vomiting in children receiving chemotherapy for solid tumors. Tropisetron iv was given 30 min before administration of chemotherapy at a dose of 5 mg in children <20 kg body weight and at a dose of 10 mg in those >20 kg. A total of 50 children were studied in 189 courses of chemotherapy. Control of emesis was defined as total in absence of acute vomiting, as major if 1 or 2 events of acute vomiting occurred, and as not controlled if >2 events of acute vomiting occurred. Response was studied, taking into account Tropisetron dosage, degree of emetogenicity of the chemotherapeutic agents in pretreated and non-pretreated patients, and according to age groups. Tropisetron, administered in a single daily dose of 8-12 mg/m(2), was found to be very effective in completely controlling acute emesis in 92% of the courses of moderately and highly emetogenic chemotherapy administered to pediatric patients with solid tumors. Moreover, Tropisetron, at this dosage, did not lead to any adverse effects.

We compared the risk of stent thrombosis (ST) after drug-eluting stents (DES) versus bare-metal stents (BMS), and tested the hypothesis that the risk of DES thrombosis is related to stent length.

Side effects, including nausea and vomiting, sore mouth , diarrhoea, hepatotoxicity, myelosuppression, and immunosuppression , are commonly encountered in patients with colorectal cancer who are treated with chemotherapy. A variety of Chinese herbal medicines have been used for managing these adverse effects.

Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.

The magnitude of the benefit of adding taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma is still unclear. The authors performed a pooled analysis as well as a meta-analysis of all Phase III trials, to determine whether the combination of anthracyclines plus taxanes provided an advantage over standard anthracyclines-based regimens.

The role of p53 in modifying sensitivity to cytotoxic drugs has been commonly studied by creating transfection pairs of wt p53 parental cells and altered p53 daughter cells, or vice versa. Authors inevitably tended to extrapolate and generalize their experimental observations, and conflicting reports have been more the rule than the exception. We have performed a meta-analysis of 356 independent studies. Average changes of drug sensitivity after a change of p53 status were observed. E6 transfection predominantly induces sensitization to cytotoxic drugs, whereas p53-/- knockout cells are more drug-resistant than their normal p53+/+ counterpart. Unexpectedly, transfection with a mutated p53 does not change much the drug sensitivity of most wt p53 cancer lines, with the notable exception of A2780, a predominant cell line in the studies analyzed (A2780 cells show increased resistance after transfection with a mutated p53). Rather interestingly, mitotic spindle poisons acted differently from other classes of cytotoxic drugs. A crucial indication of our findings is that the role of p53 alone in determining sensitivity/resistance to cytotoxic drugs is limited: the individual molecular pathology and differentiation of a given cancer line prevail over any average trend, and are causal to a broad spreading of the data. We also identify major "confounding factors", alias independent categorical variables, capable of affecting the average outcome.

Information about breast cancer treatment and prevention in African American women is scant, and recommendations for therapy from clinical trials for breast cancer are based primarily on data obtained from white women.