Economic evaluation for the UK of nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreas cancer

Background:

The combination of nab-paclitaxel plus gemcitabine (NAB-P+GEM) has shown superior efficacy over GEM monotherapy in metastatic pancreas cancer (MPC). Independent cost-effectiveness/utility analyses of NAB-P+GEM from the payer perspective have not been conducted for the UK.

Methods:

A Markov model simulating the health outcomes and total costs was developed to estimate the life years gained (LYG) and quality-adjusted life years gained (QALY) and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) for patients with MPC in a base case and in a probabilistic (PSA) sensitivity analysis. Total cost included the cost of supportive care medications, administration, chemotherapy, disease monitoring, and adverse reactions; and was discounted at 3.5% per year. A full lifetime horizon and third party payer perspective was chosen.

Results:

The total cost of NAB-P+GEM was £5466 higher than the cost for GEM. Respectively, LYGs were 0.97 vs 0.79 and QALYs were 0.52 vs 0.45, with ICER of £30 367/LYG and ICUR of £78 086/QALY, confirmed by PSA.

Conclusions:

The superior survival efficacy of NAB-P+GEM over GEM in the management of MPC is associated with positive cost-effectiveness and cost-utility.     

A prospective study of coffee intake and pancreatic cancer: results from the NIH-AARP Diet and Health Study

Background:

Evidence evaluating the association between type of coffee intake (caffeinated, decaffeinated) and risk of pancreatic cancer is limited.

Methods:

In the US NIH-AARP Diet and Health Study, we used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for coffee intake and risk of pancreatic cancer among 457 366 US adults.

Results:

Over 4 155 256 person-years of follow-up, 1541 incident first primary pancreatic cancers occurred. Following detailed adjustment for tobacco smoking history, risk estimates for coffee drinking were not statistically significant; compared with never drinkers of coffee, the hazard ratios (95% CI) were 1.05 (0.85–1.30), 1.06 (0.86–1.31), 1.03 (0.85–1.25), 1.00 (0.79–1.25), and 1.24 (0.93–1.65) for <1, 1, 2–3, 4–5, and ≥6 cups per day, respectively (P-value for trend 0.46). The observed null association was consistent across all examined strata (sex, smoking status, coffee caffeination, and prevalent diabetes).

Conclusions:

In a prospective study of coffee intake with the largest number of pancreatic cancer cases to date, we did not observe an association between total, caffeinated, or decaffeinated coffee intake and pancreatic cancer.     

Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

Background:

Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.

Methods:

Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg⁻¹ verteporfin. After 60–90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.

Results:

In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm³ at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple''s pancreaticoduodenectomy.

Conclusions:

Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.     

New-onset type 2 diabetes,elevated HbA1c,anti-diabetic medications,and risk of pancreatic cancer

Background:

Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.

Methods:

A nested case–control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.

Results:

Among 1 574 768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol⁻¹ compared with <0 mmol mol⁻¹) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72–2.72 and OR, 5.06, 95% CI 1.52–16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55–56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85–2.52), compared with no use of any anti-diabetic medications.

Conclusions:

New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.     

Phase II study of gemcitabine,oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer

Background:

Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer.

Methods:

Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0–2 were treated with panitumumab 6 mg kg⁻¹, GEM 1000 mg m⁻² (10 mg m⁻² min⁻¹) and OX 85 mg m⁻² on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival.

Results:

Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5–24 months) and median overall survival 20.3 months (95% CI 9–25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%.

Conclusions:

The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.     

Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer

Background:

The purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic.

Methods:

Temsirolimus (20 mg Kg⁻¹ daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days. Xenografts were characterised at baseline by gene expression and comparative genomic hybridisation. Patients with advanced, gemcitabine-resistant pancreatic cancer were treated with sirolimus (5 mg daily). The primary end point was 6-month survival rate (6mSR). Correlative studies included immunohistochemistry assessment of pathway expression in baseline tumours, drug pharmacokinetics (PKs), response assessment by FDG-PET and pharmacodynamic effects in peripheral-blood mononuclear cells (PBMCs).

Results:

In all, 4 of 17 xenografts (23%) responded to treatment. Sensitive tumours were characterised by gene copy number variations and overexpression of genes leading to activation of the PI3K/Akt/mTOR pathway. Activation of p70S6K correlated with drug activity in the preclinical studies. Sirolimus was well tolerated in the clinic, showed predictable PKs, exerted pathway inhibition in post-treatment PBMCs and resulted in a 6mSR of 26%. No correlation, however, was found between activated p70S6K in tumour tissues and anti-tumour effects.

Conclusion:

Sirolimus activity in pancreatic cancer was marginal and not predicted by the selected biomarker.     

Nut consumption and risk of pancreatic cancer in women

Background:

Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer.

Methods:

We prospectively followed 75 680 women in the Nurses'' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.

Results:

We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables.

Conclusion:

Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.     

Serum levels of IL-6 and IL-1β can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer

Background:

With this study, we sought to characterise the impact of pro-inflammatory cytokines on the outcomes of gemcitabine monotherapy (GEM) in patients with pancreatic cancer (PC).

Methods:

Treatment-naive patients with advanced PC and no obvious infections were eligible for enrolment. All of the patients were scheduled to undergo systemic chemotherapy. Serum pro-inflammatory cytokines were measured using an electro-chemiluminescence assay method before chemotherapy. High cytokine levels were defined as values greater than the median. Clinical data were collected prospectively.

Results:

Sixty patients who received GEM were included in the analysis. High IL-6 and IL-1β levels were poor prognostic factors for overall survival in a multivariate analysis (P=0.011 and P=0.048, respectively). Patients with both a high IL-6 level and a high IL-1β level exhibited shortened overall and progression-free survival, a reduction in the tumour control rate, and a high dose intensity of GEM compared with patients with low levels of both IL-6 and IL-1β.

Conclusion:

The serum levels of IL-6 and IL-1β predict the efficacy of GEM in patients with advanced PC.     

The frequency and severity of capecitabine-induced hypertriglyceridaemia in routine clinical practice: a prospective study

Background:

Capecitabine is known to rarely cause raised serum triglycerides (TG). In our centre, several patients receiving capecitabine developed raised TG levels corresponding to the ‘very high risk'' category for potentially serious acute pancreatitis.

Methods:

A fasting blood lipid screening protocol was introduced into clinical practice for patients receiving capecitabine. Patients with TGs >5 mmol l⁻¹ were treated and followed up. An 18-month prospective audit was performed to establish the incidence and severity of capecitabine-induced hypertriglyceridaemia (CIHT).

Results:

A total of 304 patients received capecitabine for colorectal cancer between January 2008 and June 2009. Of these, 212 patients (70%) were screened and 8 (3.7%) developed clinically significant hypertriglyceridaemia requiring lipid-lowering therapy. Two of the eight patients had diabetes and one had pre-existing dyslipidaemia. One suffered cerebral infarction during chemotherapy. There were no cases of acute pancreatitis. Follow-up showed that serum TGs safely and rapidly returned to normal with appropriate treatment without discontinuation of capecitabine.

Conclusions:

This is the first prospective study evaluating CIHT. These results suggest that it should be classed as a ‘common'' undesired effect of capecitabine. Despite this, the incidence does not justify routine screening in all patients. Targeted screening in those with diabetes or pre-existing hyperlipidaemia is recommended, together with adoption of a clear management policy.     

Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study

Background:

Studies document that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. However, studies on the direct association of magnesium with pancreatic cancer are few and findings are inconclusive. In this study, we aimed to investigate the longitudinal association between magnesium intake and pancreatic cancer incidence in a large prospective cohort study.

Method:

A cohort of 66 806 men and women aged 50–76 years at baseline who participated in the VITamins And Lifestyle (VITAL) study was followed from 2000 to 2008. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatic cancer incidence by magnesium intake categories.

Result:

During an average of 6.8-year follow-up, 151 participants developed pancreatic cancer. Compared with those who met the recommended dietary allowance (RDA) for magnesium intake, the multivariable-adjusted HRs (95% CIs) for pancreatic cancer were 1.42 (0.91, 2.21) for those with magnesium intake in the range of 75–99% RDA and 1.76 (1.04, 2.96) for those with magnesium intake <75% RDA. Every 100 mg per day decrement in magnesium intake was associated with a 24% increase in the incidence of pancreatic cancer (HR: 1.24; 95% CI: 1.02, 1.50; P_trend=0.03). The observed inverse associations appeared not to be appreciably modified by age, gender, body mass index, and non-steroidal anti-inflammatory drug use but appeared to be limited to those taking magnesium supplementation (from multivitamins or individual supplement).

Conclusions:

Findings from this prospective cohort study indicate that magnesium intake may be beneficial in terms of primary prevention of pancreatic cancer.     

Insulin-like growth factors and liver cancer risk in male smokers

Background:

The liver is the primary source of circulating insulin-like growth factor (IGF)-I, yet the relation between IGFs and liver cancer is uncertain.

Methods:

In a case–cohort study within a cohort of 29 133 male smokers we examined associations of serum IGF-I and IGF binding protein (IGFBP)-3 with liver cancer (50 cases).

Results:

Nonlinear associations between liver cancer and IGF-I and IGFBP-3 were observed (P=0.04 and P<0.01, respectively), strongest association at lowest levels (odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1–0.7 for 80 vs 30 ng ml⁻¹ of IGF-I; OR=0.2, 95% CI=0.1–0.6 for 1400 vs 700 ng ml⁻¹ of IGFBP-3).

Conclusions:

Low IGF-I and IGFBP-3 levels in male smokers are associated with increased risk of liver cancer.     

Diabetes type II,other medical conditions and pancreatic cancer risk: a prospective study in The Netherlands

Background:

To date, only a few risk factors for pancreatic cancer have been established. We examined prospectively relations between several medical conditions and pancreatic cancer incidence.

Methods:

In 1986, 120 852 participants completed a baseline questionnaire on cancer risk factors, including several self-reported physician diagnosed medical conditions. At baseline, a random subcohort of 5000 participants was selected using a case-cohort approach for analysis. After 16.3 years of follow-up, 448 pancreatic cancer cases (63% microscopically confirmed) were available for analysis.

Results:

Diabetes mellitus type II and hepatitis were positively associated with pancreatic cancer risk (multivariable-adjusted hazard ratio: 1.79; 95% confidence interval: 1.12–2.87 and hazard ratio: 1.37; 95% confidence interval: 1.04–1.81, respectively). Furthermore, a positive trend in risk with increasing years of diagnosis of diabetes (P=0.004) and of hepatitis (P=0.02) was observed. However, an inverse association was observed between hypertension and pancreatic cancer risk, this was found among microscopically confirmed cases only (hazard ratio: 0.66; 95% confidence interval: 0.49–0.90), while years since diagnosis of hypertension significantly decreased cancer risk (P for trend=0.02).

Conclusion:

In this prospective study, a positive association was observed between self-reported physician diagnosed diabetes mellitus type II and hepatitis and pancreatic cancer risk, whereas an inverse association was observed with hypertension.     

The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

Background:

The risk of cancer with hypercalcaemia in primary care is unknown.

Methods:

This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified.

Results:

Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l⁻¹. Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17–3.93, P=<0.001; positive predictive value (PPV) 11.5% females: OR 1.86, 95% CI 1.39–2.50, P<0.001: PPV 4.1%.

Conclusions:

Hypercalcaemia is strongly associated with cancer in primary care, with men at most risk, despite hypercalcaemia being more common in women.     

Physical function as a prognostic biomarker among cancer survivors

Background:

We tested the hypothesis that objectively measured physical function predicts mortality among cancer survivors.

Methods:

We assessed objectively measured physical function including the short physical performance battery (SPPB) and fast walk speed in older adult cancer survivors.

Results:

Among 413 cancer survivors, 315 (76%) died during a median follow-up of 11.0 years. In multivariable-adjusted analyses, each 1-unit increase in the SPPB score and 0.1 m s⁻¹ increase in fast walk speed predicted a 12% reduction in mortality (hazard ratio (HR): 0.88 (95% confidence interval (CI): 0.82–0.94); P<0.001, and HR: 0.88 (95% CI: 0.82–0.96); P=0.003, respectively).

Conclusions:

Objectively measured physical function may predict mortality among cancer survivors.     

Analysis of the intra- and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole

Background:

Hypoxia is thought to be an adverse feature of pancreatic cancer, but direct measurement in patients is technically challenging. To address this, we characterised the intra/interpatient heterogeneity of hypoxia in surgical specimens from patients who received the 2-nitroimidazole tracer pimonidazole pre-operatively.

Methods:

Pimondazole was given intravenously 16–20 h before pancreatectomy, and the extent and intratumoral heterogeneity of hypoxia determined by image analysis applied to multiple tissue blocks stained by immunohistochemistry. Intra/interpatient heterogeneity was estimated by variance component analysis.

Results:

Pimonidazole staining was analysed in 10 tumours. The extent of labelling varied amongst patients (0–26%), with a broader range of hypoxia in the epithelial (1–39%) compared with the stromal (1–13%) compartments. Variance component analysis demonstrated greater inter- than intrapatient variability of hypoxia, and that multiple (4–5) tumour sections are required to provide a consistent evaluation of its extent in individual tumours.

Conclusions:

There is significant intra- and intertumoral heterogeneity of hypoxia in pancreatic cancers, and these do not appear to be generally more hypoxic than other cancer types. This study establishes the feasibility to assess hypoxia in pancreatic cancer patients using pimonidazole, but questions the reliability of measurements made using a single tissue section.     

Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden

Background:

A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association.

Methods:

Hepatitis C virus- and hepatitis B virus-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIRs), and with a matched reference population using a Cox proportional hazards regression model to calculate hazard ratios (HRs).

Results:

In total 340 819 person-years in the HCV cohort and 102 295 in the HBV cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIR_HCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIR_HBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders.

Conclusion:

Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power.     

Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results

Background:

Radiolabelled antibody targeting of cancer is limited by slow blood clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves tumour localisation. The primary goals of this first pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC).

Methods:

Different dose schedules were studied in four cohorts of five patients: (1) shortening the interval between the bsMAb and peptide administration (5 days vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 μg). After confirmation of tumour targeting by ¹¹¹In-IMP288, patients were treated with a bsMAb/¹⁷⁷Lu-IMP288 cycle.

Results:

Rapid and selective tumour targeting of the radiolabelled peptide was visualised within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour targeting was achieved with a 1-day interval between the administration of the bsMAb and the peptide and with the 25-μg peptide dose. High ¹⁷⁷Lu-IMP288 doses (2.5–7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions, and transient grades 3–4 thrombocytopaenia in 10% of the patients who received ¹⁷⁷Lu-IMP288.

Conclusion:

This phase I study demonstrates for the first time that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted.     

Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Background:

Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.

Methods:

During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96–1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.

Conclusion:

Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.     

A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer

Background:

The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor.

Methods:

This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m⁻²) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus.

Results:

Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%.

Conclusion:

Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m⁻² in patients with SCLC.     

50 years of screening in the Nordic countries: quantifying the effects on cervical cancer incidence

Background:

Nordic countries'' data offer a unique possibility to evaluate the long-term benefit of cervical cancer screening in a context of increasing risk of human papillomavirus infection.

Methods:

Ad hoc-refined age-period-cohort models were applied to the last 50-year incidence data from Denmark, Finland, Norway and Sweden to project expected cervical cancer cases in a no-screening scenario.

Results:

In the absence of screening, projected incidence rates for 2006–2010 in Nordic countries would have been between 3 and 5 times higher than observed rates. Over 60 000 cases or between 41 and 49% of the expected cases of cervical cancer may have been prevented by the introduction of screening in the late 1960 s and early 1970 s.

Conclusions:

Our study suggests that screening programmes might have prevented a HPV-driven epidemic of cervical cancer in Nordic countries. According to extrapolations from cohort effects, cervical cancer incidence rates in the Nordic countries would have been otherwise comparable to the highest incidence rates currently detected in low-income countries.