Anthropometric measures at different ages and endometrial cancer risk

Background:

Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain.

Ethods:

M A case–control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models.

Results:

The OR for BMI >30 at diagnosis compared with 20 to <25 kg m⁻² was 4.08 (95% CI: 2.90–5.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43–3.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR=1.60; 95% CI: 0.52–4.96).

Conclusion:

The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age.     

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study

Background:

The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear.

Methods:

A population-based cohort of 36 959 Swedish men aged 45–79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases).

Results:

From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m^–2 when compared with 22 kg m^–2 was 0.69 (95% CI 0.52–0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88–1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51–1.01)).

Conclusion:

Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa – a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.     

Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study

Background:

Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear.

Methods:

Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression.

Results:

Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m⁻² increase in BMI, 95% confidence interval (CI): 1.77–1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09–1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77–1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61–2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88–1.22).

Conclusion:

Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women''s current BMI.     

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study

Background:

Smokers with low body mass index (BMI) may be more susceptible to lung cancer.

Methods:

We prospectively examined the association between baseline BMI and lung cancer risk in the Singapore Chinese Health Study, a cohort of 63 257 Chinese enrolled between 1993 and 1998.

Results:

After adjustment for smoking intensity and duration, BMI was inversely associated with risk of lung cancer among current smokers (P for trend=0.0004). Current smokers at different dosage of smoking with low BMI had significantly higher risk for lung cancer than those with high BMI. Hazard ratios (95% confidence intervals) of lung cancer for heavy smokers with BMI of ⩾28, 24–<28, 20–<24, and <20 kg m⁻² were 6.37 (2.10–19.30), 9.01 (5.04–16.10), 8.53 (6.35–11.5), and 11.12 (6.60–18.70), respectively, as compared with nonsmokers. BMI had no modifying effects on lung cancer risk among nonsmokers and former smokers.

Conclusion:

Smokers with lower BMI may experience an enhanced risk of lung cancer. The findings have significant public-health implication given the increase in smoking prevalence in developing countries, where people still have relatively low BMI.     

Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer

Background:

Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy.

Methods:

Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15–30 mg m⁻² per week and cisplatin 15–30 mg m⁻² per week in six planned dose levels (DLs) in 3–6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.

Results:

A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m⁻², cisplatin 15 mg m⁻²) and grade 3 nausea in DL2 (20 mg m⁻², 15 mg m⁻²). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial).

Conclusion:

Cisplatin and docetaxel each 30 mg m⁻² per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.     

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium

Background:

Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer.

Methods:

We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype.

Results:

Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30–34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99–1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01–1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m⁻²) and endometrioid subtypes (pHR: 1.08 per 5 kg m⁻²), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m⁻²) subtype, but only the association with high-grade serous cancers was significant.

Conclusions:

Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.     

Men with cancer change their health behaviour: a prospective study from the Danish diet, cancer and health study

Background:

Health behaviour changes may improve the quality of life and survival among cancer survivors. We prospectively examined changes in health behaviour among and between men with prostate cancer (PC), men with cancers other than PC and cancer-free men.

Methods:

We analysed data for 20 914 men (50–65 years), 426 with cancer, and 20 488 persons who were cancer-free between baseline (1993–1997) and follow-up (2000–2002) in multiple linear regression models to determine differences in changes in body mass index (BMI) and in alcohol and tobacco consumption.

Results

Body mass index and tobacco and alcohol consumption decreased significantly (P<0.001) between baseline and follow-up among both men with cancer and cancer-free men. Men with cancers other than PC significantly decreased their BMI (β=−058; 95% confidence interval (CI): −0.77, −0.40) and tobacco consumption (β=−1.36; 95% CI: −2.22, −0.49) compared with cancer-free men and were significantly more likely to quit smoking and lose weight.

Conclusion:

Men with cancers other than PC decreased their tobacco consumption and BMI significantly more than cancer-free men. Men with cancer do change their health behaviour; clinicians should take this into account in planning follow-up care for cancer survivors.     

Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Background:

Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.

Methods:

Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m⁻² at first infusion followed by weekly infusions of 250 mg m⁻² combined with FUFOX (oxaliplatin 50 mg m⁻², 5-FU 2000 mg m⁻², and DL-folinic acid 200 mg m⁻² d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.

Results:

Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50–79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0–10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9–11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.

Conclusion:

Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum–fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial.     

A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9605)

Background:

To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma.

Methods:

Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease. Thymic carcinoma, carcinoid or lymphoma cases were excluded. Patients received 9 weeks of chemotherapy: cisplatin (25 mg m⁻²) on weeks 1–9; vincristine (1 mg m⁻²) on weeks 1, 2, 4, 6 and 8; and doxorubicin (40 mg m⁻²) and etoposide (80 mg m⁻²) on days 1–3 of weeks 1, 3, 5, 7 and 9. Chemotherapy courses were supported by granulocyte colony-stimulating factor. Post-protocol local therapy was allowed.

Results:

From July 1997 to March 2004, 30 patients were entered. Three were ineligible due to different histology. Chemotherapy-associated toxicity was mainly haematological and was well tolerated, with no deaths due to toxicity, and 87% of patients completed the planned 9-week regimen. Overall response rate was 59%, with 16 of the 27 eligible patients achieving partial response. Median progression-fee survival (PFS) was 0.79 years (95% confidence interval: 0.52–1.40 years), and PFS at 1 and 2 years was 37 and 15%, respectively. Overall survival rates at 2 and 5 years were 89 and 65%, respectively.

Conclusion:

In stage-IV thymoma patients, weekly dose-dense chemotherapy offers similar activity to conventional regimens.     

Phase II and UGT1A1 genotype study of irinotecan dose escalation as salvage therapy for advanced gastric cancer

Background:

To assess the efficacy and safety of individualised dose optimisation of irinotecan monotherapy as salvage treatment for advanced gastric cancer (AGC).

Methods:

A total of 43 patients were enrolled. Intravenous irinotecan (350 mg m⁻²) was administered every 3 weeks. The dose was increased (425 mg m⁻² and 500 mg m⁻²) or decreased (250 mg m⁻²) depending on patient tolerance. UGT1A1 genotypes were determined by direct sequencing of genomic DNA extracted from peripheral blood.

Results:

A total of 183 cycles of irinotecan were administered, with a median of four cycles per patient. The overall response rate was 9.3%, and the disease control rate was 62.8%. Median time to disease progression was 2.8 months, and median overall survival was 8.0 months. Grade 3–4 neutropenia was the most common toxicity (53.5%), and febrile neutropenia was the least common toxicity (4.6%). Compared with defective allele groups, UGT1A1 *1/*1 was associated with a lower incidence of grade 3–4 neutropenia during the first cycle (P=0.018).

Conclusion:

Individualised irinotecan dose escalation based on patient tolerance was not associated with increased toxicity and shows modest activity as salvage chemotherapy for AGC. The role of UGT1A1 genotype in clinical toxicity requires further evaluation.     

A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours

Background:

On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study.

Methods:

A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10 mg m⁻² and was increased up to 120 mg m⁻² according to the accelerated titration method and modified Fibonacci method.

Results:

One dose-limiting toxicity (DLT) occurred in a patient who was given 90 mg m⁻² of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120 mg m⁻², which led to the conclusion that the maximum tolerated dose was 120 mg m⁻², and the recommended dose was 90 mg m⁻², although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration–time curve of ultrafilterable platinum at 120 mg m⁻² NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin.

Conclusion:

The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.     

Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer

Background:

Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m⁻² per day on days 3–16 every 3 weeks.

Methods:

Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m⁻² and an S-1 dose of 80 mg m⁻².

Results:

In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1–72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8–12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind.

Conclusion:

Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.     

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials

Background:

Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy.

Methods:

Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m⁻² over 30 min), oxaliplatin (65 mg m⁻²) and 5-FU (1500 mg m⁻² over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure.

Results:

Response rates were 19% (95% CI: 6–32%) and 23% (95% CI: 9–37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6–12.4) and 9.9 months (95% CI: 7.5–12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia.

Conclusion:

Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.     

Phase I study of lapatinib plus vinorelbine in patients with locally advanced or metastatic breast cancer overexpressing HER2

Background:

To determine the recommended doses of lapatinib (LPT) combined with vinorelbine (VNR) in women with human epidermal growth factor receptor 2-overexpressing advanced breast cancer pretreated with trastuzumab.

Methods:

In this phase I study, women were treated with oral daily LPT and i.v. VNR infused on days 1 and 8 every 3 weeks. Dose levels (DL) of LPT (mg)/VNR (mg m⁻²) ranged from 750/20 to 1250/30. The primary end point was feasibility based on maximal tolerated dose (MTD) and maximum administered dose (MAD). Pharmacokinetic interactions were investigated.

Results:

Of 33 patients included, 29 were evaluable. Two DLT occurred at DL4 (1000/25) meeting the MAD criteria. Despite an additional intermediate DL3′ (1250/22.5), MTD was reached at DL3 (1000/22.5). Grade 3–4 neutropenia was the most common toxicity (34% and 38% of patients, respectively). Other significant toxicities included grade 3–4 diarrhoea (3% each), and grade 3 asthenia (10%). Although not statistically significant, LPT (at 1000 or 1250 mg) decreased the VNR clearance by 30–40% compared with DL1.

Conclusion:

The MTD LPT 1000 mg/VNR 22.5 mg m⁻² (DL3) is recommended for additional development. Pharmacokinetic interactions might increase the exposure to VNR and consequently alter the hematological tolerance.     

Randomised, non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial

Background:

Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity.

Methods:

Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m⁻²) on days 1 and 8, cisplatin (60 mg m⁻²) on day 1, and 5-fluorouracil (200 mg m⁻² per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m⁻²) on days 1 and 8 and capecitabine (1600 mg m⁻² per day) on days 1–14, every 3 weeks (weekly TX, wTX).

Results:

A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rates of febrile neutropenia were low in each arm. Median progression-free and overall survival times were 5.9 and 11.2 months for wTCF and 4.6 and 10.1 months for wTX, respectively.

Conclusion:

Weekly TCF and TX have encouraging activity and less haematological toxicity than TCF administered 3-weekly. Weekly docetaxel-based combination regimens warrant further evaluation in this disease.     

Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts

Background:

No comparisons of different doses of docetaxel-capecitabine in patients with advanced gastric cancer have been performed.

Methods:

Patients with previously untreated metastatic/locally advanced gastro-oesophageal or gastric adenocarcinoma were enrolled in a prospective multicentre phase II trial. Two sequential cohorts received docetaxel 75 mg m⁻² (day 1) plus capecitabine 1000 mg m⁻² twice daily (days 1–14) (cohort I) or docetaxel 60 mg m⁻² (day 1) plus capecitabine 800 mg m⁻² twice daily (days 1–14) (cohort II) every 3 weeks. The primary end point was confirmed overall response rate.

Results:

In all, 91 patients were enrolled (cohort I, n=40; cohort II, n=51) and 87 were evaluable for efficacy (n=38, 49, respectively). Overall response rate was 50.0% in cohort I and 23.5% in cohort II (exploratory analysis, P=0.014). Median times to tumour progression and overall survival were 5.6 and 10.1 months in cohort I and 3.7 and 7.2 months in cohort II, respectively. Dose reductions for docetaxel and capecitabine were required in 50.0% and 57.5% of patients in cohort I and 11.8% and 15.7% in cohort II, respectively.

Conclusion:

Starting treatment with full doses and reducing promptly seems to be the more promisingly effective strategy than starting cautiously with lower doses. Docetaxel/capecitabine 75/2000 mg m⁻² is a manageable, convenient outpatient combination with promising efficacy against advanced gastric cancer.     

Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

Background:

Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine+irinotecan (2-weekly schedule), as first-line therapy of MCRC.

Methods:

Patients received irinotecan 175 mg m⁻² on day 1 and oral capecitabine 1000 mg m⁻² twice daily on days 2–8 every 2 weeks. For patients aged ⩾65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m⁻², respectively.

Results:

A total of 53 patients were enrolled: 29 (55%) were ⩾65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR + stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1–2 hand–foot syndrome in 7 (13%) patients.

Conclusion:

Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients.     

Phase I/II study of sagopilone (ZK-EPO) plus carboplatin in women with recurrent platinum-sensitive ovarian cancer

Background:

Sagopilone is the first fully synthetic epothilone in clinical development and has demonstrated promising preclinical activity. This phase I/II, prospective, open-label trial investigated the efficacy and safety of sagopilone plus carboplatin in patients with recurrent platinum-sensitive ovarian cancer (OC).

Methods:

In phase I (dose-escalation stage), patients with OC recurring at least 6 months after platinum-containing chemotherapy received 3-h infusions of sagopilone (initial dose of 12 mg m⁻²) followed by carboplatin every 3 weeks, for 2–6 treatment courses. Patients enrolled in phase II received 3-h infusions of 16 mg m⁻² sagopilone. Efficacy was assessed using modified Response Evaluation Criteria in Solid Tumors (modRECIST) and Gynecologic Cancer InterGroup CA125 criteria. The safety and tolerability of sagopilone were also evaluated.

Results:

In all, 45 patients received sagopilone at 12 mg m⁻² or 16 mg m⁻². There were 29 confirmed tumour responses (21 modRECIST and 8 CA125) across both treatment groups, indicating that the primary objective of the study was reached. The main adverse events (AEs) reported were peripheral neuropathy (75.6%), fatigue (71.1%) and nausea (64.4%). Grade ⩾3 AEs occurred in 35 patients (77.8%). No deaths related to the study drug were reported.

Conclusion:

Sagopilone in combination with carboplatin was effective and toxicities were manageable in patients with recurrent platinum-sensitive OC.     

Body mass index and the risk of meningioma,glioma and schwannoma in a large prospective cohort study (The HUNT Study)

Background:

Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS).

Methods:

In a large population study (The Nord–Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma.

Results:

A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0–25) of follow-up. In obese women (BMI ⩾30 kg m⁻²), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97–2.92, P-trend=0.05) than in the reference group (BMI 20–24.9 kg m⁻²), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ⩾25 kg m⁻²) with the risk of schwannoma (HR=0.48, 95% CI: 0.23–0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup.

Conclusion:

These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk.