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ABSTRACT: Sequential administration of chemotherapeutic drugs might have advantages: additive toxicity is avoided and the individual drugs can be given in full dosages. The Swedish group earlier found the combination of gemcitabine and carboplatin to be effective and with acceptable toxicity. The group therefore decided to add docetaxel in a sequential way in a randomized phase II study. Patients were randomized to either gemcitabine or carboplatin for six cycles or the same regimen for three cycles followed by weekly single agent docetaxel. The primary objective was time to progression (TTP). One hundred and twenty-three patients with performance status WHO 0-2 and with earlier un-treated non-small cell lung cancer with measurable stage IIIB disease, not amenable to curative treatment, or stage IV disease without known metastatic spread to the CNS, were enrolled. Hematological toxicity was more common in the GC group but clinically significant bleeding or leucopenic fever occurred only in a minority of patients. No complete responses were noted. Partial response (PR) was observed in 19.3% and 20.8% in the GC and GCD group, respectively. Progression-free survival was 5.6 and 4.8 months and overall survival time 10.6 and 10.1 months in the GC and GCD groups, respectively. Thus, sequential treatment with docetaxel after treatment with gemcitabine and carboplatin did not improve time to progression, response rates, or overall survival.
Lung cancer (Amsterdam, Netherlands) 02/2011; 71(2):178-81. · 3.14 Impact Factor
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ABSTRACT: Material from 117 consecutive patients with lung cancer was investigated with respect to serological markers for chronic Chlamydia pneumoniae infection. Specific C. pneumoniae IgA antibodies were found significantly more often in patients with lung cancer than in control groups with coronary heart disease and in healthy controls, even after adjustment for smoking. The results suggest that chronic C. pnmmoniae infection is common in patients with lung cancer.
Apmis 08/2009; 107(7‐12):828 - 832. · 1.99 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.
From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death.
Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.
The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2008; 3(11):1325-31. · 4.55 Impact Factor
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Gunnar Hillerdal
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ABSTRACT: The present paradigm is that slow-growing and clinically unimportant lung cancers are very rare. Over the years, convincing evidence for their existence in significant numbers has been dismissed, but with computerized tomography scanning being increasingly common, their reality can no longer be denied. The time is now ripe for a paradigm shift--with consequences for screening as well as clinical practice in the future. The doubling time of the tumor is probably the most important factor for survival of the patient, and research on how to measure this figure is urgent. Age, smoking habits, and comorbidities of the patient are now the main factors when discussing treatment with the patient; once we can predict the behavior of the cancer, i.e., whether it is indolent or actually threatens the patient's life, we will be able to give better advice.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2008; 3(3):208-11. · 4.55 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma (MPM) has a poor prognosis and there is limited effect of treatment. Lately, pemetrexed and cisplatin have been established as the standard treatment.
The present study was planned in 1998, when there was no standard treatment. Single-dose doxorubicine had, in small studies, accomplished remissions, and the Scandinavian Mesothelioma Groups therefore decided to test a liposomized form of this drug, which had shown limited toxicity but good efficacy in a few small studies.
Fifty-four evaluable patients with histologically verified and inoperable MPM were treated with liposomized doxorubicine 40 mg/m(2), every 4 weeks for six cycles.
In all, 29 patients (54%) received at least six treatments. The quality of life remained good during the study. Hematologic toxicity was very low. Palmo-plantar erythema occurred in 11 patients (20%), thereof 7 grade II but none was severe and none was dose-limiting. There were four partial responses (7%). The median time to progression (TTP) was 5 months, the median survival was 12 months, and at 24 months, 22% were still alive.
Liposomized doxorubicine has a low toxicity and is well tolerated; there were a remarkably long TTP and a good survival. Thus, despite the low response rate, liposomized doxorubicine remains an interesting drug for the treatment of malignant mesothelioma.
The Clinical Respiratory Journal 04/2008; 2(2):80-5. · 1.06 Impact Factor
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Gunnar Hillerdal
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ABSTRACT: The yellow nail syndrome (YNS) is the triad of 'yellow' nails, peripheral oedema and pleural effusions. For diagnosis, which is clinical, at least two of these findings are necessary. Also typical is a long-standing chronic cough often caused by low-grade bronchiectases. The pleural effusions often require pleurodesis. The pathogenesis is probably a dysfunction of the lymphatic system (1, 2). Octreotide regulates the release of growth hormone and thyrotropin, and also has effects on the gastro-intestinal tract, where it inhibits glandular secretion, neurotransmission, smooth-muscle contraction and absorption of nutrients. Adverse effects are nausea, abdominal cramps, diarrhoea, malabsorption of fat and flatulence (3). Because of the inhibition of absorption of fats and other nutrients, octreotide has been useful in chylothorax from many different causes (4). The pleural effusion in YNS is usually an exudate, but in rare cases a frank chylothorax. One such case with successful octreotide treatment has been described in the literature (5).
The aim of this report was to investigate the effect of octreotide treatment on a patient with YNS with pleural exudates not resulting from chylothorax.
A 62-year-old man with typical YNS presented with bilateral large pleural effusions (Fig. 1). He had suffered from repeated pneumonia for many years, and 10 years earlier mild bronchiectases were diagnosed and yellow nails were noted. From the right pleura, 1750-mL clear yellowish fluid was removed and a few days later, 1300 mL was removed from the left side. During the next few weeks, repeated thoracocenteses on both sides were necessary for the palliation of his dyspnoea, and the total amount of removed fluid was more than 10 L. The pleural fluid showed a low cholesterol value, 1.2 mmol/L (serum, 3.5), a fairly high albumin level, 19.0 g/L [serum, 25 g/L (normal, 36-45)], and no triglycerides. Octreotide was administered, initially 0.5 mg subcutaneously twice daily to make sure that there were no side effects, then the long-acting drug, 30 mg given every fourth week. There was a subjective improvement after the first week, and even though he still has pleural effusions bilaterally, he no longer needs palliative thoracocenteses and can live a normal life. His nails are better, as is the oedema. He is satisfied with his treatment and does not wish to have any pleurodesis. The observation time is now 6 months, and no adverse side effects have been seen so far.
Octreotide can be tried in cases of YNS before more aggressive therapies are started. However, the best results are probably achieved in the rare cases where the effusion is a chylothorax. The other symptoms, such as yellow nails and oedema, also seemed to improve but evaluation is difficult because even normally, there are variations over time with these symptoms. Pleurodesis will probably be necessary in the future for our patient despite his octreotide treatment. Further studies are warranted in this rare disease.
The Clinical Respiratory Journal 12/2007; 1(2):120-1. · 1.06 Impact Factor
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ABSTRACT: Mesothelioma can occur in different variants, some of which are difficult or impossible to differentiate from sarcomas. There are scattered reports of sarcomatous mesotheliomas that have osteogenic properties. Here, we report a 57-year old man who presented with a mediastinal tumor containing scattered irregular calcifications with some scattered pleural thickening of the right pleura. Biopsy showed a sarcoma with bone formation. The man was born in the Turkish village of Karain, where the incidence of mesothelioma is extremely high, and a sarcomatous mesothelioma was therefore diagnosed. Since the tumor was pressing against the large vessels and heart, a debulking was performed, followed by Pemetrexed and Carboplatin treatment. However, the tumor grew rapidly and spread to the pleura, involved the heart, and the patient succumbed. This is to our knowledge the first report of a sarcomatous mesothelioma with bone formation from environmental exposure to mineral fibers.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2007; 2(10):983-4. · 4.55 Impact Factor
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is associated with smoking but other etiological factors contribute. Chlamydia pneumoniae is an obligate intracellular bacterium causing both acute and chronic respiratory tract infections. Studies have revealed an association between chronic C. pneumoniae infection and COPD, asthma and lung cancer but there have been difficulties detecting C. pneumoniae in the bronchial tree. Cytospin slides prepared from bronchoalveolar lavage (BAL) fluid from 14 patients with COPD, 10 healthy smokers (S) and 7 non smokers (NS) were analyzed with a fluorescein isothiocyanate labeled monoclonal antibody to C. pneumoniae. Lung tissue from 24 patients with advanced emphysema who had undergone lung volume reduction surgery (LVRS) was examined with immunohistochemistry for C. pneumoniae. Archived serum samples for detection of specific C. pneumoniae antibodies by microimmunofluorescence were available for 30 of the BAL subjects and 11 of LVRS patients. C. pneumoniae elementary body like structures were found in 29% of cytospin specimens from COPD patients, 14% of NS and 10% of HS. C. pneumoniae was detected in lung tissue in 8%. COPD patients had higher titres of IgG and IgA than NS and S. There was no association between occurrence of C. pneumoniae in BAL fluid and antibody titres. In conclusion, the assays used for detection of C. pneumoniae in lung tissue are feasible, and could be adapted in adequately powered studies to further confirm an association between C. pneumoniae infection and COPD.
International Journal of COPD 02/2007; 2(4):643-50.
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ABSTRACT: Three patients with very similar clinical symptoms, i.e. hemoptysis and coughing up of staples some time after volume-reducing surgery, are described. There was no deterioration in lung function, nor in the patient's well-being, which could be ascribed to the coughing up of the staples. Thus, staples can some time after volume reducing surgery erode out into the bronchi and be coughed up, often with some small amounts of blood. This has no clinical significance other than the disturbing symptoms. Possibly, the calf pericardium used as strenghtener of the suture lines will with time cause an immunological reaction, causing destruction of the foreign material and thereby dislodging the staples.
Respiratory Medicine 03/2006; 100(2):371-3. · 2.47 Impact Factor
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ABSTRACT: This study investigated the possibility of pleuropulmonary lesions, which can occur as rare but serious side effects of different ergot drugs, occurring more commonly in persons earlier exposed to asbestos.
All reports of pleuropulmonary side effects of the ergot drugs used in Sweden in the Swedish side effect registry from 1985 to 2003 were studied. In addition, the literature was reviewed.
In the registry, 47 men and 3 women were found. Of the men, 24 were exposed to asbestos, and 2 denied such exposure; 2 of the 3 women were exposed. In the literature, 111 patients were found--32 had confirmed exposure and 15 denied it. For most of the patients, it was not possible to determine exposure.
Enough evidence exists to postulate that earlier asbestos exposure in combination with the intake of ergot drugs can cause pleuropulmonary lesions.
Scandinavian journal of work, environment & health 01/2006; 31(6):459-64. · 3.12 Impact Factor
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ABSTRACT: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements.
After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year.
All seven thoracic surgery centers in Sweden.
All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS.
Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively.
Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months.
In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.
Chest 12/2005; 128(5):3489-99. · 5.25 Impact Factor
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ABSTRACT: This phase III study compared overall survival in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life.
Chemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2 on days 1 and 8; gemcitabine arm) or with carboplatin (area under the curve 5 on day 1; GC arm) every 21 days.
Demographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v 11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms.
In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.
Journal of Clinical Oncology 11/2005; 23(33):8380-8. · 18.37 Impact Factor
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Gunnar Hillerdal
Lung Cancer 02/2004; 43(1):75-6. · 3.43 Impact Factor
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ABSTRACT: Autopsy studies have shown that a sizeable portion of lung cancers are never diagnosed and thus not entered into any cancer registry.
In 1997, we decided to make all available efforts to find all patients with lung cancer who had not been registered previously.
The local hospitals in the county of Gävleborg, Sweden.
All patients with lung cancer diagnosed in the county from 1997 to 2000.
In meetings with all the general practitioners of the county, these were asked to refer all suspected cases as early as possible, including those with a seemingly dismal prognosis. This initiative was also covered by the newspapers and the local television station.
From 1997 onwards, the incidence of lung cancer in the county was found to be 40-50 per 100,000 inhabitants compared with an incidence of about 30 during the ten preceding years. This difference is significant in time (P<0.0001) and is compared with the incidence of lung cancers in four neighboring counties (P=0.002).
There can be a considerable number of patients with lung cancer who are never diagnosed. This can explain differences in survival between various countries and this will also affect the results of screening programs, since the control groups will also include a number of lung cancer cases which will never be recognized.
Lung Cancer 08/2002; 37(2):137-42. · 3.43 Impact Factor
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ABSTRACT: The epidemiology of lung cancer is changing in many parts of the world. In the industrialized countries, there is a trend that the incidence in men is declining, while it is increasing for women. Also, adenocarcinomas are becoming relatively more common, especially among men. The purpose of this study was to investigate whether such trends also occur in Sweden and also to describe other aspects of an unselected lung cancer material today, such as symptoms, stage and smoking habits. In the county of Gaevleborg, Sweden, practically all patients with lung cancer are referred to the lung department, and thus a total material of lung cancer patients with only a minimal selection bias can be studied. All patients with lung cancer in the county from January 1, 1997 to December 31, 1999, were investigated prospectively regarding stage, type of cancer, and symptoms. In all, there were 364 patients, 237 (65.1%) men and 127 (34.9%) women. The mean age for men was 69.8 and for women, 68.1 years. 91.9% of the men and 78.6% of the women were smokers or ex-smokers. In general the men were heavier smokers than were the women (P<0.0001). Adenocarcinoma was the most common subtype found in women and squamous cell carcinoma in men. The excess of adenocarcinoma in women was due to never-smoking women; for smoking and ex-smoking men and women, the proportion of adenocarcinomas was the same. In all, 240 patients (68.0%) were diagnosed at Stage IIIb (27.2%) or IV (40.8%), with no significant differences between the sexes. The most common first symptom was cough. Only 7.0% of patients were asymptomatic. In conclusion, the trend of an increasing proportion of adenocarcinoma in lung cancer is seen also in Sweden. A depressingly high percentage of patients present in late stages and are thus inoperable.
Lung Cancer 04/2002; 36(1):9-14. · 3.43 Impact Factor
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ABSTRACT: It is well known that there are delays in diagnosis of lung cancer, both from the patients and from the doctors. We decided to prospectively study this in our area.
All patients with known lung cancer (134 cases) seen at the Department of Respiratory Medicine in Gaevle from February 1, 1997, to February 28, 1998, were investigated prospectively. A questionnaire recorded all symptoms, smoking habits, etc. All dates for visits to doctors and investigations were noted.
The mean delay of the patients, i.e. from the first symptom(s) until the GP was contacted, was 43 days (median 21). From the first contact with the GP until referral to the specialist the mean time was 56 days (median 33). From the first visit to the specialist to diagnosis the mean time was 33 days (median 9), with 68% of the patients diagnosed within a month. The mean time from first symptom(s) until treatment or the decision not to treat (the sum of all delays) was 203 days (median 189), i.e. around 7 months.
The delays are in most instances fairly long. With a planned approach, the delays due to the doctors could probably be shortened.
Lung Cancer 02/2002; 35(1):53-7. · 3.43 Impact Factor
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Lakartidningen 103(44):3375-6.
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Gunnar Hillerdal
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ABSTRACT: After World War II, large quantities of asbestos were imported to Sweden and used in construction and ship building. In 1976, the use of asbestos was for practical purposes prohibited. Today, the only exposures are environmental, from asbestos in place and when buildings are demolished or rebuilt, and there are very strict rules for such work. Consequently, it is assumed that the asbestos-related diseases will gradually disappear from society, but due to the long latency time, about 100 mesotheliomas still occur every year in Sweden, and so far there is no certain sign of a decrease in incidence. Compensation is from the state via general insurance and consists basically of compensation for lost income and medical costs.
International journal of occupational and environmental health 10(2):154-8. · 1.03 Impact Factor
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Gunnar Hillerdal
Lakartidningen 107(39):2301.
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Roger Tell,
Christer Sederholm,
Claes Klintenberg,
Lars Franksson,
Eva Brandén, Gunnar Hillerdal,
Ulf Lönn,
Carl-Johan Lindén,
Sven-Börje Ewers,
Kristina Lamberg,
Eva Mrazek,
Britta Lödén,
Anders Sjögren,
Thomas Linné,
Signe Friesland,
Florin Sirzén
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ABSTRACT: To evaluate weekly induction chemotherapy followed by weekly concomitant chemoradiotherapy in a multicentre phase II study of patients with unresectable stage III non-small cell lung cancer (NSCLC; stage wet IIIB excluded).
Eligible patients received three weekly cycles of paclitaxel 100 mg/m2 and carboplatin AUC2 followed by six weekly cycles of paclitaxel 60 mg/m2 and carboplatin AUC2 in combination with thoracic radiotherapy (2 Gy per fraction and day to a total dose of 60 Gy).
Sixty-four patients (40 males and 24 females) with a median age of 63 years (range, 43-79 years) entered the study. T and N stage were distributed as follows: T1 2 patients (3.2%), T2 10 patients (15.6%), T3 15 patients (23.4%), T4 37 patients (57.8%); N0 10 patients (15.6%), N1 1 patient (1.6%), N2 26 patients (40.6%), N3 26 patients (40.6%), and N missing 1 patient (1.6%). Seven patients (10.9%) suffered from grade 3/4 oesophagitis. Grade 1/2 oesophagitis occurred in 36 patients (56.3%) and pneumonitis grade 1/2 occurred in 10 patients (15.6%). Sixty-three patients were evaluated on an intent-to-treat basis. The overall response rate was 74.6%. The median time to progression was 247 days and median overall survival was 461 days. According to subgroup analyses, no statistically significant differences were noted according to gender, age (<65 vs. > or =65 years), performance status, histology, or study centre.
Induction chemotherapy followed by concurrent chemoradiotherapy with weekly cycles of paclitaxel and carboplatin is feasible and generates moderate toxicity. Efficacy is comparable to other recently published regimens. However, prognosis remains, in general, poor for this group of patients and further work to develop better therapy is required.
Anticancer research 28(5B):2851-7. · 1.73 Impact Factor
