Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain.

OBJECTIVE: This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression. PATIENTS AND METHODS: The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation. RESULTS: TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results. CONCLUSION: These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.

Is there a common etiology for the rising incidence of and decreasing survival with adenocarcinoma of the lung?

We studied possible explanations for the deteriorating survival for adenocarcinoma of the lung between 1975 and 1994 in relation with trends in incidence. The proportion of adenocarcinoma among men has been increasing since 1975 and for those born after 1920, while survival has decreased since 1975 and for those born since 1930. Among women, both the proportion of adenocarcinoma and survival have remained more or less constant. The rising incidence and the decreasing survival may both be related to changes in tobacco use, the increased use of low-tar filter cigarettes since the 1960s being the most likely candidate.

[Lung cancer in the Netherlands in the period 1989-1997: the epidemic is not over yet]. / Longkanker in Nederland in de periode 1989-1997: de epidemie is nog niet voorbij.

OBJECTIVE: To describe and interpret changes in incidence, mortality and survival of lung cancer in the Netherlands in the period 1989-1997. DESIGN: Secondary data analysis. METHODS: Data on the incidence of lung cancer were collected from the Dutch Cancer Registration (1989-1997), on mortality from Statistics Netherlands (CBS; 1989-1994), on the incidence of lung cancer in other European countries from EUROCIM (1990-1994), on survival of Dutch lung cancer patients from the Comprehensive Cancer Centre Amsterdam (1988-1997) and the Comprehensive Cancer Centre South (1988-1992) and on survival of other European lung cancer patients from EUROCARE (1985-1989). Incidence rates were calculated per 100,000 person years and standardized by age according to the European population structure. Survival was calculated as the ratio of observed survival among the lung cancer patients and the expected survival of the general population. RESULTS: The incidence of lung cancer among men decreased from 109 to 93, whereas that among women increased from 18 to 23. The incidence of lung cancer among Dutch men was high in comparison to other European countries, whereas that among women was average. The trends in lung cancer incidence were probably related to the trends in past smoking behaviour. Mortality decreased among men from 106 to 91 and increased among women from 15 to 20. Survival was better for younger patients, a localised tumour, and better for squamous cell carcinoma or adenocarcinoma than for large-cell undifferentiated or small-cell carcinoma. The relative 5-year survival was 12%, the relative 1-year survival 39%; these were good in comparison with other European countries. CONCLUSION: The incidence and mortality of lung cancer among Dutch men decreased, but still in 1997 almost 20 men in the Netherlands died each day of lung cancer. Among women the end of the increase is not in sight and in 1997 over 5 women died each day of lung cancer.

Increased but low incidence and poor survival of malignant mesothelioma in the southeastern part of The Netherlands since 1970: a population-based study.

Changes in the incidence and survival rates for malignant mesothelioma in the southeastern part of The Netherlands since 1970 were investigated, using data from the Eindhoven Cancer Registry (ECR). The exposure to asbestos in this area is presumed to be limited. Most of the mesotheliomas occurred in the pleura, where there were 119 (88%) against 15 (11%) in the peritoneum and two in the tunica vaginalis testis. Compared to other European countries, the incidence rate for the southeastern part of The Netherlands was fairly low in the second half of the 1980s. Between 1975 and 1994 the age-adjusted incidence rates (ESR) for pleural mesothelioma increased twofold (from 10 to 19 per one million person-years among men and from 2.4 to 3.8 among women). The rate for peritoneal mesothelioma remained constant. The overall relative 0.5-, 1-, and 3-year survival rates remained 68, 42, and 8%, respectively. The fourfold higher incidence rate for men compared with women reflects the fact that mesothelioma is mainly an occupational disease. In view of presumed limited exposure to asbestos and small geographical variation, the incidence of mesothelioma in the southeastern part of The Netherlands will probably remain low, despite an increase in the past decades.

Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: a population-based study.

BACKGROUND: With the rising mean age of lung cancer patients, the number of patients with serious co-morbidity at diagnosis is increasing. As a result, co-morbidity may become an important factor in both the choice of treatment and survival. We studied the prevalence of serious co-morbidity among newly diagnosed lung cancer patients and its association with morphology, stage and treatment. PATIENTS: A total of 3864 lung cancer patients registered in the population-based registry of the Comprehensive Cancer Centre South between 1993 and 1995. RESULTS: During the study period, the mean age of patients was 67 years (range: 29-93). The most frequent concomitant diseases were cardiovascular diseases (23%), chronic obstructive pulmonary diseases (COPD) (22%) and other malignancies (15%). The prevalence of concomitant diseases was highest for men (60%), patients with squamous-cell carcinoma (64%) and those with a localised tumour (66%). The resection rate for patients < 70 years, with a localised non-small-cell lung tumour, was especially low for those with COPD (67%) or diabetes (64%) compared with patients without concomitant diseases (94%). The association between co-morbidity and chemotherapy for patients with small-cell lung cancer was limited. CONCLUSIONS: The prevalence of co-morbidity, especially cardiovascular diseases and COPD, among lung cancer patients is about twice as high as in the general population. Co-morbidity seems to be associated with earlier diagnosis of lung cancer, but it may also lead to less accurate staging and less aggressive treatment. Thus, prognosis is likely to be negatively influenced by co-morbidity.

Improvement and plateau in survival of small-cell lung cancer since 1975: a population-based study.

BACKGROUND: Cytotoxic therapy appears to have improved short-term survival for patients with small-cell lung cancer, but little is known about the results for unselected patients and trends in long-term survival. PATIENTS AND METHODS: One thousand seven hundred ninety-six patients with small-cell lung cancer diagnosed between 1975 and 1994 in southeastern Netherlands. We studied treatment policy for and survival of unselected patients since 1975, when cytotoxic therapy emerged. RESULTS: The proportion patients receiving chemotherapy, with or without irradiation, almost tripled from 30% to 82% for patients younger than 70 years of age and from 15% to 56% for those over 70, whereas the proportion receiving only radiotherapy decreased from 36% to 5% in both age groups. The short-term (< 2 year) survival rate improved markedly between 1975 and 1989, especially for patients younger than 70 (median survival increased from five to 10 months). Two-year survival remained poor (8%). Two percent of all patients younger than 70 years at diagnosis survived for at least eight years, but these patients still represent an excess five-year mortality of 39%. CONCLUSIONS: In southeastern Netherlands short-term survival of patients with small-cell lung cancer improved markedly up to the end of the 1980s, but a major impact on cure rates has not been achieved.

Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since 1975.

We studied the incidence and survival rates for the histological subtypes of non-small-cell lung cancer, using data from the Eindhoven Cancer Registry over the period 1975-94. The proportions with adenocarcinoma and large-cell undifferentiated carcinoma increased from 11% to 21% and from 11% to 15%, respectively, while those with squamous cell carcinoma decreased from 78% to 62%. The increase in the proportion with adenocarcinoma was only found among men. Although the overall prognosis for patients with non-small-cell lung cancer has remained unchanged, there have been divergent changes between morphological subtypes. Relative 1- and 5-year survival rates for squamous cell carcinoma have improved slightly from 48% to 51% and from 14% to 16%, respectively, because of an increase in the proportion with localized tumours, while relative 1- and 5-year survival rates for adenocarcinoma have decreased from 59% to 45% and from 28% to 18%, respectively, because of a decrease in localized tumours. The proportion with localized tumours and the relative 1-year survival for large-cell undifferentiated carcinoma (about 18% and 30% respectively) were markedly lower. The divergent trends could partly be explained by changes in the histological classification of tumours, but changes in patterns of risk and biological behaviour of adenocarcinoma cannot be excluded.

Transmural care of terminal cancer patients: effects on the quality of life of direct caregivers.

BACKGROUND: The burden of caring for terminal cancer patients has a negative effect on the informal caregivers' quality of life. OBJECTIVES: To investigate the effects of a transmural home care intervention program for terminal cancer patients on the direct caregivers' (the patient's principal informal caregiver) quality of life, compared with standard care programs. The intervention program intended to optimize the cooperation and coordination between the intramural and extramural health care organizations (transmural care). METHODS: Direct caregivers of terminal cancer patients (estimated prognosis of less than 6 months) could be included in this quasi-experimental study. The direct caregivers' quality of life was measured in a multidimensional way 1 week before (T1), 1 week after (T2), and 4 weeks after (T3) the patient's discharge from the hospital (discharge being the starting point of the intervention), then again at 3 months after the patient's death (T4). Factor analyses on the four outcome measures yielded one factor. This was considered the primary outcome measure and was named the Overall Quality of Life Index (OQOLI). RESULTS: Multiple regression analyses showed that the intervention contributed significantly positively to the direct caregivers' OQOLI at T2 (beta=.30; p < .05) and T4 (beta=.28; p < or = .05), compared with standard care. CONCLUSION: Transmural care forms a significantly positive contribution to the OQOLI of direct caregivers of terminal cancer patients 1 week after the patient's discharge from the hospital and 3 months after the patient's death. Good terminal care also appears to be important for direct caregivers as well, with respect to perceived quality of life.

Transmural care. A new approach in the care for terminal cancer patients: its effects on re-hospitalization and quality of life.

Despite their wishes, terminal cancer patients are frequently readmitted to hospitals. This appears in part to be due to poor communication amongst professional caregivers and/or the overburdening of their (informal) caregivers. This quasi-experimental study investigated the effects of a transmural home care programme on re-hospitalization, quality of life and place of death for terminal cancer patients. The programme intended to optimize communication, cooperation and coordination between intra- and extra-mural health care organizations (transmural care). Initial patient characteristics of the intervention group (n = 79) matched those of the control group (n = 37) well. When compared to the control group, which received the standard community care, patients in the intervention group underwent significantly less re-hospitalization during the terminal phase of their illness (5.8 versus 11.5 days; P < 0.01) while the intervention contributed significantly positive to the patients' "physical" quality of life 1 month after the start of the intervention. A higher, but not significant (P = 0.06) percentage of patients in the intervention group also died at home (81 versus 65%). The introduction of measures to enhance coordination and cooperation of intra- and extramural care, seems to be an improvement compared to standard community care.