Bevacizumab 5 or 7.5 mg/kg in Metastatic Colorectal Cancer Can Be Infused Safely Over 10 Minutes

Background  

Bevacizumab is a humanized monoclonal antibody that blocks vascular endothelial factor. It demonstrated an efficacy in many cancer types. The standard recommendation of administration is the 90-, 60-, and 30-min infusion sequence for all doses. We evaluated in this study the possibility of reducing infusion time to 10 min for bevacizumab given at 5 or 7.5 mg/kg in metastatic colorectal cancer (MCRC).     

Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience

Background

Fulvestrant 500 mg is currently approved for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer after failure of prior endocrine therapies.

Methods

A total of 117 postmenopausal women with metastatic breast cancer, who experienced progression after previous endocrine therapies, were treated with fulvestrant 500 mg between January 2012 and June 2014. Clinical response, time to progression (TTP) and adverse events were investigated.

Results

Ninety-nine patients had recurrent breast cancer and 18 patients had stage IV disease. Patients had received a median of two endocrine therapies and a median of two chemotherapies, prior to fulvestrant. There were 10 patients with partial response, 39 patients with long stable disease, 18 patients with stable disease, and 50 patients with progressive disease, so that the objective response rate was 8.5 %, with a clinical benefit rate of 41.9 %. The median TTP was 6.1 months. The absence of liver metastases, a small number of previous chemotherapies, and the longer duration of first-line endocrine therapy were positively correlated with TTP in univariate analysis. In multivariate analysis, a significant association was observed between TTP and duration of first-line endocrine therapy. Serious adverse events were observed in one patient with pulmonary embolism and in one patient with psychiatric symptoms.

Conclusions

Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. Patients with acquired resistance to endocrine therapies might be good candidates for fulvestrant therapy regardless of the number of prior endocrine treatments.

     

Chirurgische Therapie im Stadium I und II des nichtkleinzelligen Lungenkarzinoms

Background

Despite modern diagnostics and multimodal treatment strategies, overall survival of lung cancer could not be significantly improved in recent decades. The majority of patients with non-small cell lung cancer (NSCLC) have distant metastases at the time of diagnosis (57%) and only approximately 40% of patients are in a potentially curable tumor stage.

Material and methods

A systematic literature search concerning original research and review articles on surgery of NSCLC in stages I and II was carried out in the PubMed database.

Results

For patients in an early tumor stage, stages I and II tumors according to the 8th edition of the Union for International Cancer Control (UICC) tumor stage classification, surgical removal of the tumor remains the therapeutic gold standard. By complete anatomical resection (lobectomy, bilobectomy or pneumonectomy) combined with a systematic mediastinal and hilar lymphadenectomy, 5?year survival rates of more than 80% in early stage IA and 48% in stage II can be achieved. In addition to open surgical resection, video-assisted, minimally invasive thoracoscopic (VATS) resection was successfully implemented worldwide for the treatment of NSCLC patients in stages I and II. For patients with stage II NSCLC, adjuvant chemotherapy was shown to improve the overall survival.

Discussion

Whether targeted therapies or immunotherapy in a neoadjuvant or adjuvant treatment modality further improve the survival of NSCLC patients in the multimodal treatment of early stage NSCLC, is currently under investigation in randomized studies.

     

Zervixkarzinom und seine Vorstufen

Background

The nomenclature of squamous and glandular precursor lesions has been reformed in the World Health Organization (WHO) classification as well as in national and international guidelines in recent years.

Methods

This study was based on a PubMed search and a review of current national and international guidelines pertaining to the subject.

Results

With regards to cervical intraepithelial neoplasia associated with human papillomavirus (HPV), an accurate distinction between low grade and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and a thorough evaluation of glandular precursor lesions are emphasized. Morphological changes associated with the productive phase of HPV infection are referred to as LSIL and changes associated with deregulation of HPV expression and of the cell cycle as HSIL; however, for the clinical management of squamous cell precursor lesions, the 3?tiered classification of cervical intraepithelial neoplasia (CIN) is still indispensable. In the differential diagnosis of HPV-associated precursors and metaplastic squamous cell and glandular lesions in particular, the relevance of p16 immunohistochemistry or combined p16/Ki-67 determination is emphasized. The staging of cervical cancer has been complemented by subdividing stage IIA into IIA1 and IIA2 and the importance of a standardized determination of morphological prognostic factors is underlined. Particular attention must be paid to differentiate special types of squamous cell carcinoma and rare non-HPV associated adenocarcinomas.

Conclusion

The recently updated recommendations and guidelines on the diagnosis and classification of cervical cancer have taken our improved understanding of the biology and natural history of the disease into account.

     

Bewältigungsstrategien in der Onkologie

Background

Coping with cancer is a great challenge for patients and their relatives. The initial shock of the diagnosis is followed by different coping strategies and phases of adaptation and processing of the situation.

Methods

This article is based on a selective literature search in PubMed on the topic of coping with disease and cancer.

Results and discussion

Psychosocial resources and factors of resilience can heIp patients to find positive perspectives apart from all the negative aspects associated with cancer. Coping with denial requires a sensitive handling by professionals bearing in mind the protective character of this coping strategy for the mental state of patients. Confrontation with reality is only a realistic option if denial results in damaging effects. Aggression and depression are antagonists in disease processing and coping strategies and are often in danger of becoming unbalanced. It must be taken into consideration that a reactive depressive mood might be an adequate state, whereas a depressive episode should be differentiated as a mental comorbidity that needs to be treated.

     

Efficacy and safety of nab-paclitaxel 125 mg/m<Superscript>2</Superscript> and nab-paclitaxel 150 mg/m<Superscript>2</Superscript> compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69)

Purpose

The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel.

Methods

Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m² (nP150) weekly, after study amendment 125 mg/m² (nP125) weekly or solvent-based paclitaxel 80 mg/m² (P80) weekly followed by epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² on day 1 for four 3-week cycles.

Results

229 patients received nP150, 377 nP125. Baseline characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for hormone receptor status, HER2 status, and Ki67. Taxane treatment was discontinued in 26.8% (nP150), 16.6% (nP125), and 13.3% of (P80) patients, respectively. Median relative total dose intensity (mRTDI) based on 125 mg/m² for nP was 103% with nP150, 95% with nP125, 99% with P80 before and 98% with P80 after the amendment. PSN grade 3–4 was observed in 14.5% of patients with nP150, 8.1% of patients with nP125 (p = 0.018), and 2.7% of patients with P80. Overall pCR before the amendment was 33.6% after nP150 and 23.5% after P80 (OR 1.65 [95% CI 1.10–2.50]; p = 0.022); pCR after the amendment was 41.4% after nP125, and 32.4% after P80 (1.48 [95% CI 1.10–1.99]; p = 0.013).

Conclusions

Nab-paclitaxel 125 mg/m² was associated with a better safety profile and compliance without compromising the efficacy compared to nab-paclitaxel 150 mg/m².

     

Saffron Can Prevent Chemically Induced Murine Skin Carcinogensis In Swiss Albino Mice

One of the most promising strategies for cancer prevention today is chemoprevention using readily available ‍natural substances from vegetables, fruits, herbs and spices . Among the spices, saffron (Crocus sativus, L) a member ‍of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological ‍studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and ‍immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin ‍papillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted with ‍croton oil were investigated. Significant reduction in papilloma formation was found with saffron application in the ‍pre-initation and post-initation periods, and particular when the agent was given both pre- and post-initation. The ‍inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes ‍like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide ‍dismutase (SOD). ‍     

Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial

Background and purpose

Fulvestrant, an oestrogen receptor (ER) antagonist with no known agonist effects, has shown activity in postmenopausal patients with ER-positive advanced breast cancer recurring or progressing following prior endocrine therapy. This double-blind, double-dummy, randomised phase III study (NCT00327769) was designed to compare the efficacy and safety of fulvestrant versus anastrozole in advanced breast cancer of Chinese postmenopausal women whose disease has progressed following prior endocrine treatment.

Materials and methods

A total of 234 patients were randomised to fulvestrant 250 mg/month (n = 121) or 1 mg/day anastrozole (n = 113), together with matching placebo. The primary endpoint was time to progression (TTP). Secondary endpoints included objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR) and time to treatment failure (TTF).

Results

Baseline characteristics were similar, with the possible exception that a higher number of fulvestrant patients had received two prior chemotherapy regimens. Median TTP was 110 days in the fulvestrant group versus 159 days in the anastrozole group (hazard ratio [HR], 1.314; 95% confidence intervals [CI], 0.948, 1.822; P = 0.101). ORR was 10% in the fulvestrant group and 14% in the anastrozole group. Median DoR from randomisation to progression was 436 days versus 432 days for the fulvestrant and anastrozole groups, respectively. CBR for fulvestrant (36.1%) versus anastrozole (48.2%) was not statistically different between the groups. TTF (110 days versus 147 days for the fulvestrant and anastrozole groups, respectively) was not statistically different between the treatments (HR, 1.307; 95% CI, 0.961, 1.778; P = 0.088). Both treatments were well tolerated, with only two patients treated with fulvestrant and four patients treated with anastrozole withdrawn from study treatment due to adverse events.

Conclusions

These data demonstrate that fulvestrant 250 mg and anastrozole were similarly effective and well tolerated in the treatment of postmenopausal Chinese women with advanced breast cancer whose disease had progressed or recurred on prior endocrine treatment.     

A Retrospective Study of Double-hit Lymphomas in Elderly Patients (Aged > 70 Years): Overall Outcomes

Background

Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies. We retrospectively studied the efficacy and tolerability of chemotherapy regimens in elderly patients within the Advocate Healthcare System.

Phase II study of S-1 plus oxaliplatin 130 mg/m<Superscript>2</Superscript> in Japanese patients with advanced gastric cancer

Purpose

Although oxaliplatin 130 mg/m² every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m² (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer.

Methods

Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0–1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥?80% relative dose intensity of oxaliplatin.

Results

Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8–86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1–19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9–8.5) and 13.1 months (95% confidence interval 7.4–19.0), respectively.

Conclusion

Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.

     

Paclitaxel-Loaded Polymeric Micelle (230 mg/m2) and Cisplatin (60 mg/m2) vs. Paclitaxel (175 mg/m2) and Cisplatin (60 mg/m2) in Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase IIB Trial

IntroductionThe development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin.Patients and MethodsPatients with stage IIIB/IV or recurrent non–small-cell lung cancer (NSCLC) who were chemonaive were eligible for participation. The patients were randomly assigned to receive PPM 230 mg/m² plus cisplatin 60 mg/m² or paclitaxel 175 mg/m² plus cisplatin 60 mg/m² once every 3-week cycle. The primary endpoint was to compare the response rate (RR) between the groups with coprimary analyses to assess noninferiority. Secondary endpoints included progression-free survival, overall survival, and safety.ResultsA total of 276 patients were randomized to PPM plus cisplatin (n = 140) or paclitaxel plus cisplatin (n = 136). RR was 43.6% in the PPM plus cisplatin group and 41.9% in the paclitaxel plus cisplatin group. Noninferiority of PPM plus cisplatin compared with paclitaxel plus cisplatin was confirmed for RR. There were no differences in progression-free survival and overall survival between the groups. Although there was a higher rate of grade 3 neutropenia in the PPM plus cisplatin group, the overall rate of adverse events was comparable between the 2 groups.ConclusionPPM in combination with cisplatin was well tolerated, and its response rate was noninferior to that of paclitaxel plus cisplatin in patients with advanced NSCLC and who were chemonaive.     

Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer

Objective:A randomized multicenter (14 centers) trial was conducted in 114 men with prostate cancer to determine whether the antiestrogen tamoxifen (Nolvadex) 20 mg or the aromatase inhibitor anastrozole (Arimidex) 1 mg prevent gynecomastia and breast pain during treatment with the non-steroidal antiandrogen bicalutamide (Casodex) 150 mg, without compromising efficacy, safety, or quality of life. Plasma samples were collected in a subgroup of these patients to investigate whether trough (pre-dose) concentrations of bicalutamide 150 mg are influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg; the results of this pilot study are reported in this article. Methods: A subpopulation of patients from a randomized placebo-controlled trial evaluating tamoxifen 20 mg and anastrozole 1 mg for the prevention of gynecomastia and breast pain in men receiving bicalutamide 150 mg for early or recurrent prostate cancer were selected on a voluntary basis from three of the trial centers. Plasma samples were collected on days 7, 14, 28, and 84 of therapy and analyzed to determine the plasma concentrations of (R)–bicalutamide and (S)-bicalutamide. In addition, plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were determined. Results: A total of 21 patients were selected. There was no significant difference between treatment groups with respect to the trough plasma concentrations of either bicalutamide enantiomer at any point during the study. Plasma concentrations of the enantiomers, and the relative proportion of the ®)- and (S)–enantiomers, were consistent with those reported in previous studies. Plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were also similar to those described elsewhere in the literature. Conclusions: The findings of this pilot study suggest that trough plasma concentrations of bicalutamide enantiomers following administration of bicalutamide 150 mg are not markedly influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg. However, an effect of tamoxifen on bicalutamide pharmacokinetics can not be completely excluded due to the size of this study. Further studies are needed to clarify the effect of tamoxifen on bicalutamide pharmacokinetics and prostate cancer control in bicalutamide-treated patients. Arimidex, Casodex, and Nolvadex are trademarks of the AstraZeneca group of companiesThis trial was sponsored by AstraZeneca (Milan, Italy)     

Vitamin B12 and Folate Status in Head and Neck Cancer

Deficiency of vitamin B12 and folate is associated with causation of certain precancerous conditions and cancer.The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214head and neck cancer patients, to evaluate the plasma vitamin B12 and folate levels to determine their associationwith tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using ahealth habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B12and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower educationand low income were among the risk factors. A decrease in the plasma vitamin B12 and folate levels with respect totobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile forvitamin B12 and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly,the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts.There was a significant positive correlation between vitamin B12 and folate levels in the subjects consuming tobacco,and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advancedas compared with early disease (ANOVA p=0.006 and Spearman’s Rho = -0.211 and p=0.01). The results suggest,potential significance of plasma vitamin B12 and folate levels in head and neck malignancies which needs to beconfirmed by further studies on a large population.     

A phase I study to determine the effect of tamoxifen on the pharmacokinetics of a single 250 mg oral dose of gefitinib (IRESSA) in healthy male volunteers

Objectives: To determine the effect of tamoxifen on the pharmacokinetics of a single 250 mg oral dose of gefitinib (IRESSA) in healthy volunteers. Methods: An open-label, single-center, phase I study in healthy male volunteers. Each volunteer received a single 250 mg oral dose of gefitinib on day 1. On days 11–14, oral loading doses of 60 mg tamoxifen were administered, followed by 20 mg tamoxifen for a further 16 days to maintain steady-state exposure. On day 24, volunteers received a second single 250 mg oral dose of gefitinib. The last dose of tamoxifen was given on day 30. Pharmacokinetic and safety assessments were conducted throughout the trial. Results: A total of 18 volunteers were recruited. The presence of tamoxifen did not have a clinically significant effect on the primary variables AUC and C_max of gefitinib, nor on the secondary variables AUC_(0-t), t_max, t_1/2, and _z. The geometric least square mean values for AUC were 3,407.6 versus 3,397.9 ng.h/ml in the absence and presence of tamoxifen, respectively (90% CL 0.894, 1.112) and for C_max were 110.8 versus 103.6 ng/ml, respectively (90% CL 0.786, 1.111). The combination of gefitinib with tamoxifen was generally well tolerated by the volunteers. There were no serious adverse events and no volunteer discontinued the study due to an adverse event. NCI-CTC grade 1/2 drug-related adverse events were observed in seven volunteers, including loose stools and skin events associated with gefitinib, and lethargy and headache, flushing, and dizziness associated with tamoxifen. Conclusions: This study suggests that tamoxifen has no significant effect on the pharmacokinetics, tolerability, or safety of a single 250 mg oral dose of gefitinib. Therefore, in clinical investigations of this combination, no dose adjustment of gefitinib is indicated.IRESSA is a trademark of the AstraZeneca group of companies     

Humane Papillomaviren und Zervixkarzinom

Background

Cervical cancer is the fourth most commonly occurring malignancy in women worldwide. Extrapolations by the Robert Koch Institute on the basis of cancer registry data in Germany showed that approximately 4600 women were diagnosed with cervical cancer in 2012.

Results

The cause of cervical cancer is a long-lasting infection with certain types of human papillomavirus (HPV) and without these viruses almost no cases of cervical cancer occur. A differentiation is made between types of virus that cause mainly warts (so-called low-risk types) and those that can trigger cancer (high-risk types). The first group includes HPV 6 and 11 and the second group includes types HPV 16 and 18, which are responsible for approximately 70?% of all cervical cancer cases. Since 2006 two vaccines have been available against the two types with the highest risk (HPV 16 and 18) and since 2015 there is a vaccine on the market that protects against five additional high-risk types (HPV 31, 33, 45, 52 and 58). This new nonavalent vaccine can prevent roughly 90?% of cervical cancers.

Conclusion

Regular participation in cervical cancer screening programs is still recommended.

     

Fulvestrant 500?mg versus anastrozole 1?mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized ‘FIRST’ study

Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II, randomized, open-label study comparing fulvestrant 500?mg with anastrozole 1?mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. At data cut-off, only 36?% of patients had progressed and the median time to progression (TTP) had not been reached for fulvestrant. Here, we report follow-up data for TTP for fulvestrant 500?mg versus anastrozole 1?mg. Key inclusion criteria were postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy. Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug. Fulvestrant was administered 500?mg/month plus 500?mg on day 14 of month 1; anastrozole was administered 1?mg/day. TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis, and investigator opinion after data cut-off. Best overall response to subsequent therapy and serious adverse events are also reported. In total, 205 patients received fulvestrant 500?mg (n?=?102) or anastrozole (n?=?103). Follow-up analysis was performed when 79.5?% of patients had discontinued study treatment. Median TTP was 23.4?months for fulvestrant versus 13.1?months for anastrozole; a 34?% reduction in risk of progression (hazard ratio 0.66; 95?% confidence interval: 0.47, 0.92; P?=?0.01). Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups. No new safety concerns for fulvestrant 500?mg were documented. These longer-term, follow-up results confirm efficacy benefit for fulvestrant 500?mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP, and, importantly, show similar best overall response rates to subsequent endocrine therapy.     

32mg恩丹西酮预防化疗所致呕吐的临床效果

[目的]观察32mg盐酸恩丹西酮预防含顺铂方案引起的恶心呕吐的临床疗效和不良反应。[方法]对120例患者采用多中心随机单盲对照试验法，分别用32mg盐酸恩丹西酮和3次8mg盐酸恩丹西酮预防呕吐。[结果]32mg盐酸恩丹西酮和3次8mg盐酸恩丹西酮第一天预防呕吐的有效率分别为85.0％和93.3％(P>0.05)，患者第一天平均呕吐次数分别为2.25±1.57次和1.83±0.96次(P>0.05)。[结论]32mg盐酸恩丹西酮与8mg盐酸恩丹西酮3次给药预防含顺铂化疗方案所致呕吐同样有效。