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Biomedical subjects

F R Hirsch

Publications and source records attributed to F R Hirsch.

At least 19 recordsLinked to original sources
PubMed2006

Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy.

BACKGROUND: Survival benefit of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is predicted by high EGFR gene copy number and by strong EGFR protein expression. Clinical relevance of these features in patients treated with chemotherapy has not been reported. PATIENTS AND METHODS: This study included 82 NSCLC patients treated with chemotherapy. There were 45% of females, 6% of never smokers and 45% of patients diagnosed with adenocarcinoma. EGFR gene copy number was evaluated by fluorescence in situ hybridization and EGFR protein level by immunohistochemistry. RESULTS: High EGFR gene copy number and protein level were found in 33% and 71% of patients, respectively. Both markers were significantly associated (P = 0.01). For objective response and disease control, there was no difference between patients defined as negative or positive for both EGFR gene copy number (P = 0.39 and P = 1.00, respectively) and for EGFR protein (P = 1.00 and P = 0.80, respectively). There were no differences in progression-free and overall survival according to EGFR gene copy number (P = 0.76 and P = 0.82, respectively) and protein level (P = 0.67 and P = 0.62, respectively). CONCLUSION: In chemotherapy-treated NSCLC patients, EGFR gene copy number was positively associated with protein level but none of the features were predictive for either treatment response or survival.

Adult↗
PubMed2006

Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib.

BACKGROUND: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib. PATIENTS AND METHODS: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry. RESULTS: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012). CONCLUSIONS: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.

Adult↗
PubMed2005

HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients.

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P=0.04) than patients with HER3- tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3- tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.

Antineoplastic Agents↗
PubMed2004

Chemoprevention of lung cancer--from biology to clinical reality.

Lung cancer is the commonest cause of cancer death in developed countries and throughout the world. Cigarette smoking is the main risk factor for lung cancer and ex-smokers today comprise approximately 50% of all new lung cancer cases. Chemoprevention builds on the concepts of field of cancerization and multistep carcinogenesis and can be defined as the use of natural or chemical compounds to prevent, inhibit or reverse the process of carcinogenesis. So far, chemoprevention studies in lung cancer have failed to reduce lung cancer mortality. New developments in biotechnology have made it possible to define more accurately high-risk populations, make earlier diagnosis possible, and allow more specific targeted therapies to be developed. Both the development and validation of biomarkers, for the selection of high-risk study populations and for response evaluation in chemoprevention studies, are important for the faster turnover of studies evaluating new agents. This article reviews the current status and describes the perspectives for new approaches in the chemoprevention of lung cancer.

Anticarcinogenic Agents↗
PubMed2002

High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer.

PURPOSE: E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in non-small-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. PATIENTS AND METHODS: Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (alpha)-, beta (beta)-, and gamma (gamma)-catenin, p120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). RESULTS: Absent or severely reduced membranous expression for E-cad, alpha-, beta-, and gamma-catenin, and p120 were observed in 10%, 17%, 8%, 31%, and 61% of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, beta-catenin, gamma-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and gamma-catenin. Besides the traditional clinical prognostic variables, E-cad and alpha-, beta-, and gamma-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. CONCLUSION: Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.

Adenomatous Polyposis Coli Protein↗
PubMed2002

Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas.

HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials.

Aged↗
PubMed2002

Role of biomarkers for early detection of lung cancer and chemoprevention.

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage. Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments. Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes. The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.

Biomarkers↗
PubMed2001

Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study.

BACKGROUND: There are no currently approved methods for the screening and early detection of lung cancer. We compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions in a randomized trial in which both the order of the procedures and the bronchoscopists were randomly assigned. METHODS: The study included high-risk subjects enrolled because of a cigarette smoking history of at least 30 pack-years, an air-flow obstruction, and either an abnormal sputum cytology (n = 48) or a previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. All statistical tests were two-sided. RESULTS: A total of 391 biopsy specimens were taken from the 55 patients. Thirty-two patients (58%; 95% confidence interval [CI] = 44% to 71%) had at least one biopsy with moderate or severe dysplasia, and 19 (59%; 95% CI = 41% to 76%) of these patients could be diagnosed based solely on the results of LIFE. LIFE was statistically significantly more sensitive than WLB for detecting moderate dysplasia or worse (68.8% versus 21.9%, respectively) (difference = 46.9%; 95% CI = 25% to 68%; P< .001). The relative sensitivities (WLB = 1.0) were 3.1 (95% CI = 1.6 to 6.3) for LIFE and 3.7 (95% CI = 1.9 to 7.3) for LIFE and WLB combined. LIFE was less specific than WLB (69.6% versus 78.3%, respectively; P = .45), but the difference was not statistically significant. The relative specificities (WLB = 1.0) were 0.9 for LIFE (95% CI = 0.6 to 1.3) and 0.6 (95% CI = 0.4 to 1.0) for LIFE and WLB combined. The results were similar regardless of the order of the procedures or the order of the bronchoscopists. Also, LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB (detection ratio [DR], which indicates the relative likelihood of getting a positive result in a sample with dysplasia compared with one without, for LIFE = 1.39 [95% CI = 1.17 to 1.65] versus DR for WLB = 0.67 [95% CI = 0.38 to 1.21]). CONCLUSION: LIFE was more sensitive than WLB in detecting preneoplastic bronchial changes in high-risk subjects. The prognostic implication of this finding is not yet clear.

Adult↗
PubMed2001

[Lung cancer screening--what now?].

BACKGROUND: Lung cancer is the most common cause of cancer death in developed countries. Because of the lack of efficient diagnostic tools for early detection and of efficient treatment for advanced disease, the prognosis of lung cancer is generally poor, with 10-15% surviving 5 years after diagnosis. Still, the majority of patients present with advanced disease. Stage IV disease is beyond cure and stage III disease is rarely curable with current therapies. Over the course of the last decade, rapid advances in molecular biology, pathology, bronchoscopy and radiology have provided a rational basis for earlier diagnosis and improved outcome. MATERIAL AND METHODS: This article reviews recent advances in the early detection of lung cancer by low-dose spiral CT scanning. The review is based on a literature search in Medline and data presented at the 3rd International Conference on Screening for Lung Cancer in New York in October 2000. RESULTS: The most promising advent has been the development of low-dose spiral CT as a screening tool for lung cancer. The advantage of this method is the possibility of diagnosing small peripheral tumours before they have spread to regional or distant areas. INTERPRETATION: A shift in the therapeutic paradigm from targeting clinically manifest advanced lung cancer towards asymptomatic preinvasive and early invasive cancer is occurring. If the altered stage distribution (87% stage I) as seen in three non-randomized population-based studies is real, CT screening may raise the lung cancer cure rate above 60%.

Clinical Trials as Topic↗
PubMed2001

Superiority of high-dose platinum (cisplatin and carboplatin) compared to carboplatin alone in combination chemotherapy for small-cell lung carcinoma: a prospective randomised trial of 280 consecutive patients.

PURPOSE: A prospective randomized trial in small-cell lung cancer (SCLC) was performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields higher response rates and survival, than carboplatin alone in a combination chemotherapy regimen. PATIENTS AND METHODS: Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by stage of disease, LDH and performance status. The treatment was in arm A: three courses induction chemotherapy with carboplatin (AUC = 4, day 1), cisplatin (35 mg/m2, days 2 and 3), teniposide (50 mg/m2, day 1-5), vincristine (1.3 mg/m2, day 1) every four weeks, followed by cyclophosphamide (3 g/m2, day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m2, day 112), and finally one course cisplatin, carboplatin, teniposide and vincristine, (days 140-144). Arm B also comprised a total of six courses, identical to those in arm A except for omission of cisplatin. RESULTS: There were no significant differences in the overall treatment outcome for A vs. B, in terms of response rates (72% in both arms), complete response rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both the CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0.05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in the high-dose platinum arm compared to the carboplatin alone arm. CONCLUSIONS: The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.

Adult↗
PubMed2001

Review of recent advances in fluorescence bronchoscopy in early localization of central airway lung cancer.

Centrally located lung cancers are radiologically occult until so far advanced as to have a low cure rate or require extensive resection for cure, but at a cost of high morbidity. These cancers represent about one-fifth of new lung cancers. Autofluorescence bronchoscopy appears to be an important tool in localizing premalignant and early malignant lesions in the large central airways, particularly when applied to high-risk patients. Applications include studies of molecular biology of premalignancy and early malignancy, chemoprevention studies, endobronchial therapy studies, localization of synchronous tumors, estimation of the extent of field cancerization, and better estimation of resection margins. Autofluorescence bronchoscopy appears to be significantly more sensitive than white light examination but has low specificity. This technology is likely to gain widespread use when evaluation of sputum for malignant changes is both more sensitive and specific, and when its application is demonstrated to reduce mortality in this important subgroup of non-small cell lung cancer patients.

Bronchoscopy↗
PubMed2001

Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology.

Lung cancer is the most common cause of cancer death in developed countries. The prognosis is poor, with less than 15% of patients surviving 5 years after diagnosis. The poor prognosis is attributable to lack of efficient diagnostic methods for early detection and lack of successful treatment for metastatic disease. Most patients (>75%) present with stage III or IV disease and are rarely curable with current therapies. Within the last decade, rapid advances in molecular biology, pathology, bronchology, and radiology have provided a rational basis for improving outcome. These advancements have led to a better documentation of morphological changes in the bronchial epithelium before development of clinical evident invasive carcinomas. This has changed our concept of lung carcinogenesis and emphasized the multistep carcinogenesis approach on several levels. Combined with the technical developments in bronchoscopic techniques, e.g., laser-induced fluorescence endoscope (LIFE) bronchoscopy, we now have improved methods to localize preinvasive and early-invasive bronchial lesions. With the LIFE bronchoscope, a new morphological entity (angiogenic squamous dysplasia) has been recognized, which might be an important biomarker and target for antiangiogenic chemopreventive agents. To reduce the mortality of lung cancer, these new technologies have been taken into the clinic in different scientific settings. The use of low-dose spiral computed tomography in the screening of a high-risk population has demonstrated the possibility of diagnosing small peripheral tumors that are not seen on conventional X-ray. A shift in the therapeutic paradigm from targeting advanced clinically manifest lung cancer toward asymptomatic preinvasive and early-invasive cancer is occurring. The present article reviews the recent advances in the diagnosis of preinvasive and early-invasive cancer to identify biomarkers for early detection of lung cancer and for chemoprevention studies.

Aged↗
PubMed2001

Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents.

Overexpression of the Her-2/neu oncogene and receptor protein was reported in approximately 20% of breast cancers and was associated with a poor prognosis. Her-2/neu expression was a predictor for response to trastuzumab, a monoclonal antibody that recognizes the Her-2/neu cell surface receptor. Data regarding the expression of Her-2/neu in lung cancer are far more limited, and there is little information regarding the influence of Her-2/neu expression and response to trastuzumab alone or in combination with chemotherapeutic agents. In this report we evaluated Her-2/neu gene expression by fluorescence in situ hybridization (FISH) and the cell surface expression of the Her-2/neu receptor by immunohistochemistry using the HercepTest and by FACS analysis in 31 lung cancer cell lines with 5 breast cancer cell lines as controls. By FACS, we found Her-2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 non-small cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung cancer (SCLC) cell lines, and 4 of 5 breast cancer cell lines. A positive HercepTest (2+ or 3+) was found in 6 of 19 NSCLC cell lines (26%, 2+; 5%, 3+), 1 of 3 SCLC cell lines (33%), and 4 of 5 breast cancer cell lines (80%). One of 6 NSCLC cell lines examined (17%) had gene amplification with >32 copies of Her-2/neu/cell and had homogeneous staining regions. One NSCLC cell line had a maximum of 14 copies of Her-2/neu/cell, and 3 had modest increases in Her-2/neu gene copy number without gene amplification (maximum 5-8 copies/cell). None of the SCLC cell lines had more than a maximum of 4 copies/cell, whereas the 2 breast cancer cell lines had maximum Her-2/neu copy numbers of 80 and 5, respectively. Aneusomy rather than true amplification was the major cause of increased Her-2/neu expression in most of the NSCLC cell lines. There was a strong correlation when the results of fluorescence-activated cell sorter, HercepTest results, and FISH were compared in pairs. Furthermore, Trastuzumab produced a G(1) cell cycle arrest and growth inhibition only in cell lines expressing Her-2/neu. The IC(50) for growth inhibition was correlated with cell surface Her-2/neu expression. The combination of trastuzumab and chemotherapeutic agents produced more than additive growth inhibition in cell lines expressing Her-2/neu, but the level of additivity was not related to the amount of Her-2/neu expression. These data indicate that trastuzumab alone and in combination with chemotherapeutic agents should be tested in NSCLC patients and that Her-2/neu should be assessed by both immunohistochemistry and FISH methods in these studies to determine which test is the best predictor of outcome.

Antibodies, Monoclonal↗
PubMed2000

Incidence of lung cancer in Denmark: historical and actual status.

This is a registry-based analysis of 97,281 lung cancer patients diagnosed in Denmark during the period 1943-1994. The development of lung cancer incidence in Denmark in the study period is described and this information is used to predict the future trends in lung cancer in Denmark. Since 1960, lung cancer has been the most frequent type of cancer in Danish men, excluding skin cancer. The incidence in men reached its maximum in 1985, when it was 100 new cases per 100,000 inhabitants, whereafter the incidence began to level off and was 83 per 100,000 inhabitants in 1994. During the study period, the incidence of lung cancer in Danish women was somewhat lower than in men. The incidence in women has been steadily increasing since 1960 by approximately 20% per each 5-year period, and was 46 per 100,000 inhabitants in 1994. Adenocarcinoma is the most frequent histological subtype in women and the only subtype increasing in incidence in men. Taking the actual development into account, the incidence of lung cancer will continue to fall among men and rise among women, leading to a reversal of the classical gender ratio in about 15 years.

Adenocarcinoma↗
PubMed2000

A dose escalating study of topotecan preceding cisplatin in previously untreated patients with small-cell lung cancer.

BACKGROUND: The aim was to define the MTD of topotecan (TPT) given before cisplatin in patients with previously untreated SCLC. PATIENTS AND METHODS: Alternating cycles A and B to a total of 6 cycles were given. Cycle A: TPT days 1-5 and cisplatin (50 mg/m2) day 5. Cycle B consisted of teniposide, carboplatin, vincristine, and cisplatin. TPT was escalated at doses 0.75, 1.0, 1.25, and 1.5 mg/m2. DLT was defined for the first cycle as grade 4 neutropenia with fever or when lasting > 7 days, or grade 4 thrombocytopenia. RESULTS: Fifteen patients with limited disease and six patients with extensive disease were included. No episodes of DLT were recorded in the first cycles A and consequently 1.5 mg/m2 was defined as MTD. At 1.5 mg/m2 (11 patients, 30 cycles), four and three episodes of grade 4 thrombocytopenia and neutropenia lasting more than seven days occurred in subsequent cycles A. Thrombocytopenia and anaemia were cumulative as more cycles were administrated. Non-hematological toxicity was mild. The response rate was 86% (95% confidence interval (95% CI): 64%-97%) with 33% (95% CI: 15%-57%) achieving CR. CONCLUSIONS: 1.5 mg/m2 TPT can be delivered safely with 50 mg/m2 cisplatin on day 5 in patients with previously untreated SCLC.

Adolescent↗
PubMed2000

Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer.

PURPOSE: To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. RESULTS: A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P: <.01) and less peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia (P: <.01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Primary lung cancer in Denmark. Historical and current developmental tendencies].

This study describes the development of lung cancer incidence in Denmark based on analysis of the Danish Cancer Registry database containing files on 97,281 lung cancer patients diagnosed in 1943-1994 in Denmark. Since 1960, lung cancer has been the most frequent type of cancer in Danish men, excluding skin cancer, the incidence reached its maximum in 1985, being 100 new cases per 100,000 inhabitants, but thereafter the incidence began to level off. During the study period, the incidence of lung cancer in Danish women was somewhat lower than in men, but increasing and was in 1994 46 per 100,000 inhabitants. Adenocarcinoma is the most frequent histological subtype in women and is the only histological subtype in men that is increasing in incidence. In conclusion, a decrease has been observed in the incidence of lung cancer among Danish males while the incidence of lung cancer in Danish women is increasing. Taking the actual development in incidence into account, the incidence of lung cancer will continue to fall among men and rise among women, leading to a reversal of the classical gender ratio in about 15 years.

Adenocarcinoma↗