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Biomedical subjects

N Van Zandwijk

Publications and source records attributed to N Van Zandwijk.

At least 19 recordsLinked to original sources
PubMed2006

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer.

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

Adolescent↗
PubMed2006

The psychological impact of annual chest X-ray follow-up in head and neck cancer.

CONCLUSION: Annual post-treatment screening of head and neck squamous cell carcinoma (HNSCC) patients for second primary lung cancer and metastatic recurrence appeared to form no major burden for head and neck cancer patients. A majority of patients regard the annual chest X-ray as a reassurance. Given these results a more intensive screening program seems psychologically justifiable for this group. OBJECTIVE: To assess the psychological impact of annual post-treatment screening for second primary lung cancer and metastases in HNSCC patients. PATIENTS AND METHODS: In a cohort of 106 patients, 68 men and 38 women, with a mean age of 56, the impact of the yearly chest radiograph was evaluated by means of a nine-item questionnaire. RESULTS: In all, 90% of the patients were in favor of annual post-treatment screening, 2% would not like to receive this screening, and 8% had no preference. A majority (98%) considered the screening as an extra medical check and 76% felt reassured. Although 21% of the patients were very nervous about the outcome of the screening, only 3% wanted to avoid the yearly chest X-ray for this reason.

Adult↗
PubMed2004

Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer.

BACKGROUND: Trastuzumab provides significant clinical benefits in HER2-positive metastatic breast cancer patients when administered in combination with chemotherapy. Chemotherapy has also been shown to be beneficial in some patients with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II trial examined the effect of adding trastuzumab to a standard chemotherapeutic combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC. PATIENTS AND METHODS: Patients with untreated stage IIIB/IV HER2-positive NSCLC received up to six 21-day cycles of gemcitabine 1250 mg/m(2) (days 1 and 8) and cisplatin 75 mg/m(2) (day 1). Patients in the trastuzumab arm received trastuzumab 4 mg/kg intravenously (i.v.) followed by 2 mg/kg/week i.v. until progression. RESULTS: Of 619 patients screened, 103 were eligible. Fifty-one patients were treated with trastuzumab plus gemcitabine-cisplatin and 50 with gemcitabine-cisplatin alone. Efficacy was similar in the trastuzumab and control arms: response rate 36% versus 41%; median time to progression 6.3 versus 7.2 months; and median progression-free survival (PFS) 6.1 versus 7 months. Response rate (83%) and median PFS (8.5 months) appeared relatively good in the six trastuzumab-treated patients with HER2 3+ or fluorescence in situ hybridization (FISH)-positive NSCLC. Addition of trastuzumab to gemcitabine-cisplatin was well tolerated, side-effects were as expected, and trastuzumab did not exacerbate the known toxicity of gemcitabine and cisplatin. Symptomatic cardiotoxicity was observed in one trastuzumab-treated patient. Serum trastuzumab concentrations in the presence of gemcitabine-cisplatin were comparable to those of trastuzumab alone. CONCLUSIONS: Trastuzumab plus gemcitabine-cisplatin is well tolerated. Clinical benefit was not observed. Although HER2 3+/FISH-positive patients may benefit from trastuzumab, the subgroup is too small to provide definitive information. No significant effect of gemcitabine-cisplatin on trastuzumab pharmacokinetics was observed.

Adult↗
PubMed2001

[Therapeutic strategies in neoadjuvant therapy of non-small cell lung cancer: benefits of gemcitabine].

Stages of non-small cell lung cancer (NSCLC) that are potential candidates for surgical resection have been treated in several ways: surgery alone is curative in only two-thirds of cases and post-operative radiotherapy (RT) provides only weak control of advanced-stage disease. Since metastatic recurrence is due to the presence of micrometastases, chemotherapy (CT) can be envisaged, even at an early stage of the disease--first with the CT/RT induction combination, which improves survival (median survival: 15 months) and the resection rate (70%). Recent studies on neoadjuvant therapy have evaluated the usefulness of different induction CT regimens. Among these, the gemcitabine/cisplatin study protocol (GC), set up in a phase II study for patients with stage IIIA N2 NSCLC, was very effective [objective response (OR): 70.2%; median survival: 19 months] and should be promising for stages IB and II. Other studies involving platinum analogs have shown good OR rates inducing a high resection rate and a reduction in the spread to mediastinal lymph nodes. Major studies are ongoing, one of which compares GC + surgery versus surgery alone (stages IB-IIIA); the other regimen aims to evaluate GC versus paclitaxel/carboplatin as well as two induction strategies.

Antimetabolites, Antineoplastic↗
PubMed2000

Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in mouth floor and buccal mucosa cells of smokers and nonsmokers.

Tobacco smoking is a major risk factor for oral cancer; mouth floor and buccal mucosa are among the most and least cancer-prone subsites, respectively, in the oral cavity. We investigated the applicability of immunohistochemistry of smoking-induced DNA adducts in oral cells for assessing the exposure to carcinogens, and estimating the risk for oral cancer. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were measured in mouth floor and buccal mucosa cells of smokers (n = 26) and nonsmokers (n = 22) by means of a semiquantitative immunoperoxidase assay. Smokers had elevated levels of PAH-DNA adducts compared to nonsmokers in their mouth floor cells (0.045 +/- 0.022 versus 0.022 +/- 0.016, P = 0.0008 arbitrary units of immunohistochemistry) as well as in their buccal mucosa cells (0.058 +/- 0.028 versus 0.028 +/- 0.012, P = 0.001). Also, there was a correlation between the levels of PAH-DNA adducts in mouth floor cells and those in buccal mucosa cells (r = 0.4, P = 0.01). Furthermore, PAH-DNA adduct levels in both mouth floor and buccal mucosa cells were significantly related to current smoking indices (amount of tar and number of cigarettes consumed per day). Expectedly, the levels of PAH-DNA adducts neither in mouth floor cells nor in buccal mucosa cells, both being short-lived cells, were related to smoking history index (pack years). The levels of PAH-DNA adducts, however, in mouth floor cells as the cancer prone cells were lower than those in buccal mucosa cells (0.037 +/- 0.023 versus 0.044 +/- 0.026, P = 0.04). We conclude that immunohistochemistry of PAH-DNA adducts in oral cells can be used for exposure assessment of tobacco-related carcinogens, however, it cannot be used for oral cancer risk estimation.

Adult↗
PubMed2000

Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955).

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.

Adult↗
PubMed1998

Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers.

The 32P-post-labelling assay for DNA adduct quantification gives the opportunity to examine endogenous exposure to DNA reactive compounds. Most human biomonitoring studies applied white blood cells (WBC) or cells obtained by broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what cell type represents the most reliable indicator for exposure to cigarette smoke-associated genotoxins. At first, we examined DNA adduct levels by means of nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides, n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/- 0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0 +/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/- 0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or = lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol-enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in granulocytes using butanol enrichment. Thirdly, dose-response relationships were investigated in mononuclear white blood cells (MNC, i.e. monocytes plus lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78). Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P < 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but after correction for age this relationship was lost. Butanol extraction resulted in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL-DNA of the same individuals yielded only 2-fold higher adduct levels. The two enrichment procedures of 32P-post-labelling were correlated in BAL cells (r = 0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates for the detection of smoking-related DNA adducts.

Adult↗
PubMed1998

The role of prognostic factors and oncogenes in the detection and management of non-small-cell lung cancer.

Like other epithelial tumors, non-small-cell lung cancer (NSCLC) is a result of a series of genetic and epigenetic changes that eventually progress to invasive cancer. The order and timing of these changes, involving specific chromosomal locations, oncogenes, and tumor-suppressor genes, have become important areas of translational research. It is hoped that this research will lead to "very early" diagnosis and "very early" treatment of non-small-cell lung cancer, and to the identification of patients with poor prognostic tumor characteristics who may be helped by additional treatment. The recognition of persons with inherited predisposition to lung cancer is also on the horizon, and, together with the molecular characterization of lung cancer, brings with it a promise of improved treatment results.

Biomarkers↗
PubMed1997

32P-postlabelling of aromatic DNA adducts in white blood cells and alveolar macrophages of smokers: saturation at high exposures.

DNA adducts may serve as a molecular dosimeter of exposure to cigarette smoke-associated carcinogens such as polycyclic aromatic hydrocarbons (PAH). Target tissues for cigarette smoke-induced carcinogenesis are rarely accessible; therefore, peripheral blood cells or cells obtained by bronchoalveolar lavage (BAL) may be used as surrogate sources of exposed DNA. However, the relationship between cigarette smoke exposure and aromatic-DNA adducts in white blood cells and BAL cells is still unclear. In this study, we examined DNA adduct formation in lymphocytes and BAL cells in several populations of smoking individuals by means of 32P-postlabelling. Significant correlations between the amount of cigarettes smoked per day and the level of aromatic-DNA adducts were found in lymphocytes. In BAL cells, DNA adduct levels were associated with age (p = 0.05) and gender (p = 0.10) after adjustment for smoking behaviour. Adduct formation levelled off at higher exposure levels, suggesting less efficient adduct formation; decreases in the formation of adducts per unit of exposure were found in lymphocytes (r(s) = -0.80, p < 0.001) and BAL cells (r(s) = -0.72, p < 0.001). To assess intra-individual variation in adduct levels at constant smoking behaviour, sampling was repeated after a period of 2 and 6 months. In lymphocytes, repeated measurements with an interval of 2 months were highly correlated (r = 0.84, p = 0.009, n = 8), whereas repeated measurements with an interval of 6 months showed no correlation (r = 0.30, p = 0.27, n = 16). Repeated measurements in BAL cells showed a significant correlation after 6 months (r = 0.68, p = 0.03, n = 10). Furthermore, in a group of occupationally exposed aluminium workers, adduct levels in total white blood cells were correlated with the average concentrations of PAH in the ambient air of workers who smoked cigarettes, whereas in non-smokers, no such relationship was found. We conclude that cigarette smoking may directly or indirectly influence DNA adduct levels and saturation of DNA adduct formation may occur, leading to non-linear dose-response relationships.

Adult↗
PubMed1997

Cisplatin/paclitaxel vs cisplatin/teniposide for advanced non-small-cell lung cancer. The EORTC Lung Cancer Cooperative Group. The European Organization for Research and Treatment of Cancer.

A total of 332 patients with advanced non-small-cell lung cancer were randomized by the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC) to receive one of two cisplatin (Platinol)-based chemotherapy regimens: Paclitaxel (Taxol) 175 mg/m2 given by 3-hour infusion followed by cisplatin 80 mg/m2 on day 1; Or cisplatin 80 mg/m2 on day 1, followed by teniposide (Vumon) 100 mg/m2 given on days 1, 3, and 5. Cycles were repeated every 3 weeks. Preliminary analysis of the results of this phase III trial shows that hematologic toxicity was decidedly more severe in the group treated with cisplatin/teniposide than in those given paclitaxel/cisplatin. Of 264 patients evaluable so far, responses have been observed in 47% of those given paclitaxel and in 29% of those treated with teniposide. However, extramural radiologic response evaluation is still under way, so these figures are expected to change somewhat. It appears clear that the paclitaxel-based therapy affords a benefit in terms of response and toxicity, but survival results are premature and any definite conclusions await final analysis.

Adolescent↗
PubMed1995

Heat and moisture exchangers as a treatment option in the post-operative rehabilitation of laryngectomized patients.

A multi-institutional, prospective clinical study was undertaken to investigate whether the use of a heat and moisture exchanger (HME) in the period following total laryngectomy could prevent the development or reduce the severity of respiratory symptoms. Fifty-nine patients from three hospitals were provided with HMEs, either immediately post-surgery or, in the case of post-surgical radiotherapy, upon completion of the radiotherapy. For the total sample (n = 59) statistically significant improvements over time (between 3 and 6 months) could be found in forced expectoration (P < 0.05), in the perceived voice quality (P < 0.001), social anxiety (P < 0.001), social interactions (P < 0.001) and in feelings of anxiety and depression (P < 0.05). Repeated measures analysis of variance indicated statistically significant group differences over time in forced expectoration and stoma cleaning (P < 0.05). No statistically significant differences over time were noted between the regular and non(regular) HME user groups in voice quality or in various aspects of daily living.

Humans↗
PubMed1995

Long-term pulmonary function after total laryngectomy.

In 58 laryngectomized patients pulmonary function tests were performed during a routine visit to the outpatient clinic. The assessment of pulmonary function with an extratracheal device could easily and reliably be accomplished in all instances. The results show that in long-term follow-up post-laryngectomy expiratory lung function values are significantly lower than predicted. Of the various subjective respiratory complaints, only a higher frequency of coughing was statistically significantly associated with decreased lung function values (P < 0.01). Neither time since surgery (> 1 year vs < 1 year), nor radiation therapy seemed to be correlated with the pulmonary function outcomes. In contrast, the age of the patient did have a significant influence. Although an age-related decline in pulmonary function is a well documented phenomenon, an additional adverse effect was suggested by the present series in the group who was over 65 years of age. Bronchodilator treatment was found to significantly ameliorate several pulmonary function parameters in a sub-group of 18 patients. It may be concluded, that after total laryngectomy significant abnormalities in pulmonary function have to be anticipated. We have found that these disturbances seem to be more pronounced with increasing age.

Age Factors↗
PubMed1991

Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma.

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.

Alkaline Phosphatase↗
PubMed1991

Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma.

We investigated the expression of the neural cell adhesion molecule (NCAM) in a series of surgically resected lung carcinomas of various histological subtypes by means of a panel of monoclonal antibodies recognising different N-CAM epitopes. In a subgroup of 56 tumours, the results of immunostaining with MAb 123C3--the antibody studied most extensively in our material--were compared to the ultrastructure, and in 231 radically resected non-small cell carcinomas, with histological tumour type and with clinical follow-up data. N-CAM expression was not limited to neuroendocrine tumours, as assessed ultrastructurally. Non-small cell lung carcinomas positive for MAb 123C3 showed post-operative overall and disease-free survival times significantly shorter than 123C3-negative non-small cell carcinomas.

Antibodies, Monoclonal↗
PubMed1990

Physical and psychosocial consequences of total laryngectomy.

The incidence and severity of respiratory symptoms after total laryngectomy and their influence on daily living were studied in 59 laryngectomized patients. Daily sputum production was the principal complaint of these patients (98%), followed by coughing (64%) and the need for frequent forced expectoration (more than 5 times a day) in order to clear the airway (57%). Frequent stoma cleaning (more than 5 times a day) was required by 37% of the patients. Significant correlation was found between respiratory symptoms, voice rehabilitation and several aspects of daily living, including fatigue, sleep problems, social contacts and psychological distress. These findings indicate that respiratory symptoms after total laryngectomy are both frequent and troublesome. The development of effective methods for minimizing and/or preventing such respiratory problems would contribute significantly to improving the quality of life of laryngectomized patients.

Aged↗