To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer.
...Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight.
Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05).
There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.
Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) ...and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone. Menopausal symptoms are significant but are not worse than those seen in older premenopausal women.
To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).
Patients with AS in the Swiss Clinical Quality Management cohort ...with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis.
A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97).
TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.
Abstract Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 ...trial. In BIG 1-98 patients were randomized to receive adjuvant (A) 5-years tamoxifen, (B) 5-years letrozole, (C) 2-years tamoxifen followed by 3-years letrozole, or (D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B + C; N = 65) vs. tamoxifen (A + D; N = 55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z -scores = 0.28, P = 0.04, 95% CI: 0.02, 0.54, Cohen’s D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their ...sequential combination, and to investigate differential effects by age.
We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were randomly assigned to receive six courses of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy, ovarian suppression with goserelin for 24 months, or six courses of classical CMF followed by 18 months of goserelin. We report QOL data collected during 3 years after random assignment in patients without disease recurrence.
Overall, patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF. There were no differences at 3 years after random assignment according to treatment except for hot flashes. As reflected in the hot flashes scores, patients in all three treatment groups experienced induced amenorrhea, but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy. Younger patients (< 40 years) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy, while those who received CMF showed marginal changes from their baseline hot flashes scores.
Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment, such as considering the trade-offs between delayed endocrine symptoms, but higher risk of permanent menopause with chemotherapy, and immediate but reversible endocrine symptoms with goserelin, in younger premenopausal patients.
Background
Functional outcomes of different reconstruction techniques have an impact on patients’ quality of life (QoL), but information on long-term QoL is lacking. We compared QoL among three ...reconstruction techniques after total mesorectal excision (TME).
Methods
Quality of life was assessed within a randomized, multicenter trial comparing rectal surgery using side-to-end anastomosis (SEA), colon J-pouch (CJP), and straight colorectal anastomosis (SCA) by the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) before randomization and every 6 months up to 2 years post-TME. The primary QoL endpoint was the change in the Trial Outcome Index (TOI), including the FACT-C subscales of physical and functional well-being and colorectal cancer symptoms (CSS), from baseline to month 12. Pair-wise comparisons of changes from baseline (presurgery) to each timepoint between the three arms were analyzed by Mann–Whitney tests.
Results
For the QoL analysis, 257 of 336 randomized patients were in the per protocol evaluation (SEA = 95; CJP = 63; SCA = 99). Significant differences between the reconstruction techniques were found for selected QoL scales up to 12 months, all in favor of CJP. Patients with SEA or SCA reported a clinically relevant deterioration for TOI and CSS at 6 months, those with SCA for CSS also at 12 months after TME. Patients with CJP remained stable.
Conclusions
Although the three reconstruction techniques differ in their effects on QoL at months 6 and 12, these differences did not persist over the whole observation period of 24 months. Patients with a colon J-pouch may benefit with respect to QoL in the short-term.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
To explore the effect of comedication with conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) on drug retention and clinical effectiveness of tumor necrosis factor ...inhibitors (TNFi) in patients with axial spondyloarthritis (SpA).
Methods
The study included all patients starting treatment with a TNFi in a large prospective cohort of axial SpA patients (Swiss Clinical Quality Management in axial SpA). Crude drug retention was analyzed using the Kaplan‐Meier method, and in adjusted analyses, Cox proportional hazards regression was used to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time.
Results
A total of 2,765 TNFi treatment courses were included from 1,914 patients with axial SpA, 20.4% in combination with a conventional synthetic DMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months) compared to the cotherapy group (39.1 months) (P = 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95% confidence interval 95% CI 1.01–1.35). This effect was even larger when only infliximab‐treated patients were considered, with an HR for monotherapy of 1.36 (95% CI 1.06–1.74). Clinical response rates were almost identical at 1 year, with a change in the Bath Ankylosing Spondylitis Disease Activity Index of −2.02 and −2.00 (P = 0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using C‐reactive protein of −1.14 and −1.12 (P = 0.45) in the monotherapy and cotherapy groups, respectively.
Conclusion
We demonstrate an association between the combination of a TNFi with conventional synthetic DMARDs and improved drug retention in patients with axial SpA, particularly in the subgroup of patients with infliximab.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
We aimed to explore the return to work (RTW) experience of individuals in remission from extremital sarcoma.
Methods
Using a qualitative survey design, we asked sarcoma survivors about ...their RTW experiences after treatment. Seven men and eight women (n = 15), 43 years old in average, participated. The majority had soft tissue sarcoma (n = 14) and no amputations (n = 14). We analysed data thematically through an inductive approach.
Results
Participants' motivation to RTW and their experiences of this transition could be understood under the main theme of “searching for distraction and wanting to leave the disease behind,” followed by “problems of the new normal.” RTW was the next step after treatment; however, being back at the same workplace/institution was challenging due to the interference of the effects of the disease and treatments and peer perceptions. In other subthemes, we identified that RTW was facilitated by different “signs of readiness,” as well as by “motivating factors and the meaning of having an occupation.”
Conclusions
Readiness to RTW while primarily an autonomous decision can also be guided by third parties, including treating physicians. RTW can be challenging, since changes in performance as well as comments from peers become a constant reminder of the status prior to the illness. Given that RTW helps distract from the disease, these reminders can be confronting and highlight the role of health professionals and employers in preparing survivors and peers to facilitate the RTW.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
•Prostate Cancer.•Salvage Radiotherapy.•Dose intensification.•Erectile Dysfunction.•Patient Reported Outcome Measures (PROMs).
To evaluate effects of dose intensified salvage radiotherapy (sRT) on ...erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP).
Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT.
344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm.
ED after RP is a known long-term side effect with significant impact on patients’ QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.
ClinicalTrials.gov. Identifier: NCT01272050.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
