To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion high-dose chemotherapy (HD-CT arm) ...to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC).
Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual.
One hundred thirty-one patients were included in this analysis. The complete response rates in the HD-CT and in the BEP arm did not differ: (intention to treat) 44.6% versus 33.3% (P = 0.18). There was no difference in FFS between the two treatment arms (P = 0.057, 66 events). At 2 years, the FFS rate was 44.8% 95% confidence interval (CI) 32.5–56.4 and 58.2%, respectively (95% CI 48.0–71.9); but this 16.3% (standard deviation 7.5%) difference was not statistically significant (P = 0.060). Overall survival did not differ between the two groups (log-rank P > 0.1, 47 deaths).
This study could not demonstrate that high-dose chemotherapy given as part of first-line therapy improves outcome in patients with poor-prognosis GCC.
Background: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC ...treatment is examined in long-term survivors.
Patients and methods: In a national follow-up study (1998–2002), 1463 TC survivors (diagnosed 1980–1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) ≤850 mg (n = 376) and Cis >850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition.
Results: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6–4.7. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3–3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status.
Conclusion: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.
Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one ...injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment.
Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7×glomerular filtration rate+25 mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214.
885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3·0–4·9), relapse-free survival rates for radiotherapy and carboplatin were similar (96·7% 95% CI 95·3–97·7
vs 97·7% 96·0–98·6 at 2 years; 95·9% 94·4–97·1
vs 94·8% 92·5–96·4 at 3 years, respectively; hazard ratio 1·28 90% CI 0·85–1·93, p=0·32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy–chemotherapy) were −1·0% (90% CI −2·5 to 0·5) by direct comparison of proportions, and 0·9% (−0·5 to 3·0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1·96% 95% CI 1·0–3·8
vs 0·54% 0·1–2·1, p=0·04). One seminoma-related death occurred after radiotherapy and none after carboplatin.
This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.
To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities.
One thousand eight hundred fourteen patients treated for ...unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose < or = 850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromsø Population Study (n = 2,847).
At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension.
Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls.
One of the aims of the European Palliative Care Research Collaborative (EPCRC) is to achieve consensus on a classification system for cancer pain. We performed a systematic literature review to ...identify existing classification systems and domains/items used to classify cancer patients with pain. In a systematic search in the databases Medline and Embase, covering 1986–2006, 692 hits were obtained. 92 papers were evaluated to address pain classification. Six standardised classification systems were identified; three of them systematically developed and partially validated. Both pain characteristics and patient characteristics relevant for cancer pain classification were included in the classification systems. All but one of the standardised systems aim at predicting treatment response or adequacy of treatment. Several domains and items used to describe cancer pain but not formally described as part of a classification system were also identified and systematised. The existing approaches to pain classification in cancer patients are different, mostly not thoroughly validated, and none is widely applied. An internationally accepted classification system for cancer pain could improve research and cancer pain management. This systematic review suggests a need for developing an international consensus on how to classify pain in cancer patients.
Background
Even though validation studies of the WHO analgesic ladder have indicated that the simple approach of the analgesic ladder can provide adequate pain control in most patients, prevalence ...studies have documented a high prevalence of pain in cancer patients. Little is known about how analgesics are actually prescribed for cancer pain. The aim of the study was to study prescriptions of analgesics during the entire disease trajectory in patients dying from cancer within five years of diagnosis.
Methods
Complete national data from the Norwegian Cancer Registry, the Norwegian Prescription Database, the Cause of Death Registry and Statistics Norway were used to study prescriptions of analgesics in a complete study population of all patients dying from cancer within five years of diagnosis in Norway from 2005 to 2009.
Results
Of a total of 10,977 subjects who received prescriptions for analgesics between diagnosis and death, 56% started analgesic treatment at step I of the analgesic ladder, 29% started at step II and 14% started at step III. Of the patients starting at step I, 28% continued to step II, 37% bypassed step II and moved directly to step III whereas the remaining 35% remained at step I. Approximately 60% received one or more dispensed prescription of a step III analgesic during the disease trajectory, whereas nearly 20% remained at step I and 20% at step II respectively.
Conclusion
The study indicates that clinicians seem to individually tailor analgesic treatment instead of applying the stepwise approach in the WHO analgesic ladder.
Significance
Complete national data covering the complete disease trajectory in cancer patients dying within five years of diagnosis. The majority of patients do not receive treatment in concordance with the stepwise approach suggested by the WHO analgesic ladder.
Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and ...services in participating centres and (2) characteristics of patients in PC programmes.
This was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme.
30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21-97); median Karnofsky score 70 (10-100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) <3 months from inclusion and 701 (68%) within 6 months. ANOVA and χ
tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (p<.0.001).
There is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research.
ClinicalTrials.gov Identifier: NCT01362816.
Abstract Context The use of unidimensional pain scales such as the Numerical Rating Scale (NRS), Verbal Rating Scale (VRS), or Visual Analogue Scale (VAS) is recommended for assessment of pain ...intensity (PI). A literature review of studies specifically comparing the NRS, VRS, and/or VAS for unidimensional self-report of PI was performed as part of the work of the European Palliative Care Research Collaborative on pain assessment. Objectives To investigate the use and performance of unidimensional pain scales, with specific emphasis on the NRSs. Methods A systematic search was performed, including citations through April 2010. All abstracts were evaluated by two persons according to specified criteria. Results Fifty-four of 239 papers were included. Postoperative PI was most frequently studied; six studies were in cancer. Eight versions of the NRS (NRS-6 to NRS-101) were used in 37 studies; a total of 41 NRSs were tested. Twenty-four different descriptors (15 for the NRSs) were used to anchor the extremes. When compared with the VAS and VRS, NRSs had better compliance in 15 of 19 studies reporting this, and were the recommended tool in 11 studies on the basis of higher compliance rates, better responsiveness and ease of use, and good applicability relative to VAS/VRS. Twenty-nine studies gave no preference. Many studies showed wide distributions of NRS scores within each category of the VRSs. Overall, NRS and VAS scores corresponded, with a few exceptions of systematically higher VAS scores. Conclusion NRSs are applicable for unidimensional assessment of PI in most settings. Whether the variability in anchors and response options directly influences the numerical scores needs to be empirically tested. This will aid in the work toward a consensus-based, standardized measure.
Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well ...documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged <or=55 years. The patients represented three principal treatment strategies: 1962/1969 (period 1): radiotherapy only; 1970/1979 (period 2): radiotherapy with or without noncisplatin-containing chemotherapy; 1980/1997 (period 3): surgery only or radiotherapy or cisplatin-based chemotherapy. Patients were censored when they reached the age of 60 years. Patients not dying from MGCT displayed significantly increased SMRs for respectively diseases of the circulatory system (SMR: 1.2, 95% confidence interval (CI): 1.0-1.5), benign gastrointestinal disorders (SMR: 2.1, 95% CI: 1.1-3.5) and nongerm cell malignancies (SMR: 2.0, 95% CI: 1.7-2.4). The SMRs for diseases of the circulatory system were similar in the three observation periods, whereas the highest SMR for benign gastrointestinal disorders was observed in patients from period 2. The risk of dying from a nongerm cell malignancy was increased both in periods 2 and 3. In conclusion, although the overall SMR for diseases of the circulatory system is increased in MCGT survivors, the introduction of cisplatin-based chemotherapy into the treatment of MGCT has so far not resulted in increased death rates due to these conditions. Patients with MGCT have a significantly increased relative death risk due to a second nongerm cell cancer, even after the introduction of modern treatment principles with overall reduction of radiotherapy. The increased death risk due to benign gastrointestinal disorders, probably related to radiotherapy, requires future in-depth analysis.
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