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NCI CANCERLIT® Search: Small Cell Lung Cancer - January 2002
National Cancer Institute®
Ultima Vez Modificado: 1 de enero del 2002
Table of Contents
1
UI - 11357499
AU - Schumacher T; Brink I; Mix M; Reinhardt M; Herget G; Digel W; Henke M;
TI -
Moser E; Nitzsche E
FDG-PET imaging for the staging and follow-up of small cell lung cancer.
SO - Eur J Nucl Med 2001 Apr;28(4):483-8
AD - Division of Nuclear Medicine, Albert Ludwigs University, Medical Center,
Freiburg, Germany. tschumacher@uhbs.ch
The staging procedures for small cell lung cancer do not differ
appreciably from those for other forms of lung cancer. For practical
purposes, the TNM stages are usually collapsed into a simple binary
classification: limited disease and extensive disease. This study was
performed to answer the question of whether fluorine-18 labelled
2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging
permits appropriate work-up (including both primary and follow-up
staging) of patients presenting with small cell lung cancer, as compared
with currently recommended staging procedures. Thirty-six FDG-PET
examinations were performed in 30 patients with histologically proven
small cell lung cancer. Twenty-four patients were examined for primary
staging while four were imaged for therapy follow-up only. Two patients
underwent both primary staging and up to four examinations for therapy
follow-up. Static PET imaging was performed according to a standard
protocol. Image reconstruction was based on an ordered subset
expectation maximization algorithm including post-injection segmented
attenuation correction. Results of FDG-PET were compared with those of
the sum of other staging procedures. Identical results from FDG-PET and
the sum of the other staging procedures were obtained in 23 of 36
examinations (6x limited disease, 12x extensive disease, 5x no evidence
of disease). In contrast to the results of conventional staging, FDG-PET
indicated extensive disease resulting in an up-staging in seven
patients. In one patient in whom there was no evidence for tumour on
conventional investigations following treatment, FDG-PET was suggestive
of residual viability of the primary tumour. Furthermore, discordant
results were observed in five patients with respect to lung, bone, liver
and adrenal gland findings, although in these cases the results did not
affect staging as limited or extensive disease. Moreover, FDG-PET
appeared to be more sensitive for the detection of metastatic
mediastinal and hilar lymph nodes and bone metastases. Finally, all
findings considered suspicious for tumour involvement on the other
staging procedures were also detected by FDG-PET. It is concluded that
FDG-PET has potential for use as a simplified staging tool for small
cell lung cancer.
2
UI - 11392578
AU - Jones AM; Hanson IM; Armstrong GR; O'Driscoll BR
TI -
Value and accuracy of cytology in addition to histology in the diagnosis
of lung cancer at flexible bronchoscopy.
SO - Respir Med 2001 May;95(5):374-8
AD - Department of Cardio-Respiratory Medicine, Hope Hospital, Salford, UK.
andmarkj@hotmail.com
There is still disagreement as to the value and reliability of wash and
brush cytology, in comparison with histology, for the diagnosis of
malignancy at flexible bronchoscopy. The present study compares the
yield and concordance of findings from the two modalities for visible
tumours at flexible bronchoscopy. A single-centre study of 514
consecutive flexible bronchoscopy procedures, in which a lesion
suspicious of cancer was seen and bronchial wash cytology, brush
cytology and forceps biopsy samples were taken. All equivocal or
suspicious results were taken as negative. An overall yield of 89.3% was
achieved using a combination of all three tests. This was greater for
endobronchial than submucosal (95% vs. 86%) tumours. Cytology alone
diagnosed 17.7% of cases. Use of all three modalities allowed tumours to
be differentiated between small and non-small cell types in all but
5/459 positive cases (98.9%). There were only 3/313 cases in which there
was a difference in cell type (small cell vs. non-small cell) between
the two modalities. We conclude that wash and brush cytology are
valuable tools, in addition to forceps biopsy, at flexible bronchoscopy.
All three tests should be performed routinely in cases of suspected
malignancy.
3
UI - 11419031
AU - Argiris A; Murren JR
TI -
Advances in chemotherapy for small cell lung cancer: single-agent
activity of newer agents.
SO - Cancer J 2001 May-Jun;7(3):228-35
AD - Northwestern University Medical School and Robert H. Lurie Comprehensive
Cancer Center, Chicago, Illinois, USA.
Small cell lung cancer (SCLC) is a common neoplasm with an extremely
poor prognosis. Patients with extensive-stage disease have a 5-year
survival rate of 1% to 2%. Identification of new active chemotherapy
agents is of great importance for the development of more effective
treatment for SCLC. Several new drugs that have established a role in
the management of non-SCLC in the past decade are also active in SCLC.
The mean response rates in untreated versus previously treated patients
for these newer drugs are: 26% versus 14% for vinorelbine, 27% versus
14% for gemcitabine, 45% versus 29% for paclitaxel, 22% versus 25% for
docetaxel, 39% versus 19% for topotecan, and 50% versus 16% to 24% for
irinotecan. A comparison of the response rates of those agents to more
established drugs (e.g., cisplatin and etoposide) suggests that the
newer drugs are equally or more active in previously treated patients
with SCLC. This activity is even more impressive because initial therapy
during the past decade has almost always included platinum and/or an
epipodophyllotoxin in the regimen. Furthermore, a recent randomized
trial showed that the combination of a newer agent (irinotecan) with
cisplatin was superior to a standard etoposide and cisplatin regimen in
patients with newly diagnosed extensive-stage SCLC. These data support
further evaluation of the newer chemotherapeutic drugs, and especially
the camptothecins (irinotecan and topotecan) and the taxanes (paclitaxel
and docetaxel), in the initial treatment of SCLC.
4
UI - 11432613
AU - Berghmans T; Paesmans M; Sculier JP
TI -
The role of cisplatin in the treatment of small-cell lung cancer?
SO - Ann Oncol 2001 May;12(5):585-6
5
UI - 11432623
AU - Hirsch FR; Osterlind K; Jeppesen N; Dombernowsky P; Ingeberg S; Sorensen
TI -
PG; Kristensen C; Hansen HH
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.
SO - Ann Oncol 2001 May;12(5):647-53
AD - Rigshospitalet, Finsen Center, Department of Oncology, Denmark.
Fred.Hirsch@UCHSC.edu
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
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.
6
UI - 11445877
AU - Machado Paschoal ME; Da Gloria Da Costa Carvalho M
TI -
Alteration of A549 carcinoma cell protein synthesis profile induced by
lung cancer patient serum.
SO - Int J Mol Med 2001 Aug;8(2):211-5
AD - Laboratorio de Oncologia Molecular, Servico de Pneumologia, Hospital
Universitario Clementino Fraga Filho, Brasil.
Several elements such as circulating DNA and metastatic cells,
containing the same primary tumor mutations, oncogenic proteins,
cytokines, and other tumor related not yet identified factors, can be
found in the blood stream of cancer patients. In this study we have
shown that serum factors presented in lung cancer patients can modify
the protein profile of the lung adenocarcinoma cell line (A549). This
alteration in cellular protein profile can be an important event in the
cell phenotype modification necessary for the advance of the disease.
There have been no similar studies regarding cancer cell protein
synthesis induction by human cancer serum.
7
UI - 11491167
AU - Park J; Kim DS; Shim TS; Lim CM; Koh Y; Lee SD; Kim WS; Kim WD; Lee JS;
TI -
Song KS
Lung cancer in patients with idiopathic pulmonary fibrosis.
SO - Eur Respir J 2001 Jun;17(6):1216-9
AD - Dept of Pulmonary Medicine, Asan Medical Center, School of Medicine,
University of Ulsan, Seoul, Korea.
Idiopathic pulmonary fibrosis (IPF) was reported to be associated with
increased risk of lung cancer as a result of the occurrence of atypical
or dysplastic epithelial changes in fibrosis which progressed to
invasive malignancy. In that situation, the cancer will develop in the
area of major fibrosis. To investigate the direct relationship between
fibrosis and cancer development, the real concordance rate of the two
lesions in the chest computed tomography (CT) was analysed and compared
to the histological types of lung cancer. The subjects included 63
patients with combined lung cancer and IPF (IPF-CA), 218 patients with
lone IPF, and 2,660 patients with primary lung cancer. All patients were
diagnosed at Asan Medical Center during the same period. The age,
percentage of smokers, and the male sex were significantly higher in
IPF-CA compared with lone IPF. The odds ratio of smoking was 2.71
compared to nonsmoking IPF controls. In IPF-CA, 56% of the cancer was
located in the periphery of the lung and 52% in the upper lobe. The
majority of the cancers (64%) were found in the nonfibrotic area at
chest CT. The most frequent cell type was squamous cell carcinoma (35%),
and there was no significant difference in the cancer cell type between
IPF-CA and total lung cancer population. These findings suggest that in
combined lung cancer and idiopathic pulmonary fibrosis patients, the
features of the lung cancer are similar to the total lung cancer
population.
8
UI - 11497234
AU - Fukuoka M
TI -
Role of topoisomerase I inhibitors in small-cell lung cancer.
SO - Oncology (Huntingt) 2001 Jul;15(7 Suppl 8):9-13
AD - 4th Department of Internal Medicine, Kinki University School of
Medicine, Osaka, Japan. mfukuoka@med.kimdai.ac.jp
Combination chemotherapy is the cornerstone of treatment that confers a
meaningful survival benefit for patients with small-cell lung cancer.
However, because there have been no major therapeutic advances for
small-cell lung cancer during the last decade, more effective new
treatments are necessary to improve the outcome of therapy. Irinotecan
(CPT-11, Camptosar), a topoisomerase I inhibitor, is one of the new
active agents that provide hope for more effective therapies. In
single-agent phase II studies, irinotecan yielded response rates between
16% and 47% in patients with previously treated small-cell lung cancer.
A phase II study of irinotecan in combination with cisplatin (Platinol)
resulted in a response rate of 86% and a median survival of 13.0 months
in patients with extensive-disease small-cell lung cancer. A phase III
trial that was conducted by the Japan Clinical Oncology Group (JCOG)
clearly demonstrated a survival advantage for the combination of
irinotecan and cisplatin vs the standard regimen of etoposide (VP-16,
VePesid) and cisplatin. Based on these results, the irinotecan and
cisplatin combination is a new standard regimen in the treatment of
extensive-disease small-cell lung cancer.
9
UI - 11504283
AU - Psyrri A; Murren J
TI -
Small cell lung cancer: strategies to optimize chemotherapy response.
SO - Cancer J 2001 Jul-Aug;7 Suppl 1():S28-34
AD - Section of Medical Oncology, Yale University School of Medicine, New
Haven, Connecticut 06511, USA.
During the past two decades, a major focus of clinical research in small
cell lung cancer (SCLC) has been the manipulation of the dose and
schedule of the available active cytotoxic agents. Approaches tested
include alternating cyclic combination chemotherapy, increasing the dose
intensity of chemotherapy with or without the support of either
cytokines or stem cells, and increasing the dose density by delivering
treatment at shorter intervals. Overall, the results of clinical trials
testing these approaches have been disappointing. One of the
difficulties in intensifying treatment for SCLC is that the patients
tend to be elderly and have smoking-related pulmonary and cardiovascular
comorbidities. In fact, as treatment regimens have become more
intensive, several multicenter groups have identified a dramatic
increase in early-treatment-related mortality rates. Yet, toxicity
associated with dose-intensification may obscure a potential therapeutic
advantage in unselected patients. Therefore, some of these groups have
performed retrospective analyses to identify factors that predict
excessive treatment-related toxicity that can be used for patient
stratification in clinical trials. This article reviews the data
regarding the role of dose-intensified therapy in the treatment of SCLC.
We propose that delivery of the currently available chemotherapy drugs
at greater dose intensity, if excessive toxicity is avoided, may offer a
meaningful improvement in survival, and that clinical trials that
appropriately test this hypothesis are warranted.
10
UI - 11504075
AU - Yuksel M; Cermik TF; Karlikaya C; Salan A; Cakir E; Gultekin A; Berkarda
TI -
S
Monitoring the chemotherapeutic response in primary lung cancer using
99mTc-MIBI SPET.
SO - Eur J Nucl Med 2001 Jul;28(7):799-806
AD - Department of Nuclear Medicine, Trakya University Medical Faculty,
Edirne, Turkey. mahmuty@trakya.edu.tr
Prediction and evaluation of the response to chemotherapy (CTx) are
important for the correct and cost-effective treatment of patients with
primary lung cancer. Although fluorine-18 fluorodeoxyglucose positron
emission tomography (FDG-PET) is accepted as the most useful and
accurate nuclear medicine technique for this purpose, its expense and
limited availability restrict its use. Compared with PET agents,
technetium-99m methoxyisobutylisonitrile (MIBI), which is used in
nuclear oncology, is cheaper and available in any nuclear medicine
clinic. With this in mind, in this study we aimed to evaluate the role
of 99mTc-MIBI in monitoring the chemotherapeutic response in primary
lung cancer. Twenty patients with primary lung cancer underwent
99mTc-MIBI single-photon emission tomography (SPET) at 15 min (early)
and 3-4 h (delayed) after injection of the tracer. All patients
underwent 99mTc-MIBI SPET study twice: before and after the 3rd cycle of
CTx. Patients were divided into two groups, responders [R(+), n=10] and
nonresponders [R(-), n=10], according to the change in tumour size on CT
scan taken 2 weeks after the last cycle of the CTx. From the SPET images
early and delayed tumour/lung ratios (ER and DR) were obtained before
and after CTx. In the R(+) group, ER and DR decreased significantly
after CTx, from 3.28+/-1.55 to 1.78+/-0.72 (P<0.04) and from 3.23+/-1.55
to 2.0+/-0.88 (P<0.05), respectively. However, in the R(-) group, while
ER showed a slight and statistically insignificant increase after CTx
(from 2.51+/-1.23 to 2.65+/-1.86), DR increased significantly, from
2.74+/-1.37 to 3.27+/-2.31 (P<0.03). The percentage decreases in ER and
DR in the R(+) group after CTx was significantly higher than that in the
R(-) group: 34.36%+/-26.7% vs -13.78%+/-27.58% (P<0.0002) and
29.45%+/-25.23% vs -18.58%+/-20.51% (P<0.0005), respectively. Using a
decrease of > or =10% as a threshold for monitoring the chemotherapeutic
response, 99mTc-MIBI had a sensitivity of 90% and a specificity of 100%.
We found a positive correlation in 14 patients between ER and DR and
survival: r=0.6754 and P=0.008, and r=0.5755 and P=0.031, respectively.
Our results suggest that 99mTc-MIBI might be used in routine practice to
monitor the chemotherapeutic response in patients with primary lung
cancer, especially when PET is not available.
11
UI - 11509120
AU - Ishikawa N; Oguri T; Isobe T; Fujitaka K; Kohno N
TI -
SGLT gene expression in primary lung cancers and their metastatic
lesions.
SO - Jpn J Cancer Res 2001 Aug;92(8):874-9
AD - Second Department of Internal Medicine, Hiroshima University Faculty of
Medicine, Minami-ku, Hiroshima 734-8551, Japan. tetsuogu@yahoo.co.jp
Cancer cells show increased glucose uptake and utilization in comparison
with their normal counterparts. Glucose transporters play an important
role in glucose uptake. We previously reported the differential gene
expression of the GLUT family in primary and metastatic lesions of lung
cancer. To investigate the role of Na( +) / glucose cotransporter (SGLT)
genes in cancers, we examined the levels of expression of SGLT1 and
SGLT2 genes in primary lung cancers and their metastatic lesions.
Ninety-six autopsy samples (35 primary lung cancers, 35 corresponding
normal lung tissues, 10 metastatic liver lesions, and 16 metastatic
lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2
expression by reverse transcription (RT)-polymerase chain reaction
(PCR). There were no significant differences in the level of expression
of either gene between the primary lung cancers and normal lung tissues.
The level of SGLT1 expression in the metastatic lesions and primary lung
cancers did not differ significantly. The level of SGLT2 expression was,
however, significantly higher in the metastatic lesions of both the
liver and lymph node than in the primary lung cancers. These results
suggest that SGLT2 plays a role in glucose uptake in the metastatic
lesions of lung cancer.
12
UI - 11557123
AU - Agelaki S; Kakolyris S; Palamidas P; Kouroussis C; Mavroudis D; Kalbakis
TI -
K; Georgoulias V; Raptis A
A dose escalation study of topotecan in combination with epirubicin in
pretreated patients with small-cell lung cancer.
SO - Lung Cancer 2001 Oct;34(1):133-9
AD - Department of Medical Oncology, University General Hospital of
Herakijon, Crete, Greece.
PURPOSE: To define the dose-limiting toxicities (DLTs) and the maximum
tolerated doses (MTDs) of topotecan in combination with epirubicin in
pretreated patients with small-cell lung cancer (SCLC). PATIENTS AND
METHODS: Twenty-seven SCLC patients with performance status (WHO) of 0-2
and adequate renal, hepatic, and bone marrow function who had failed
EP-containing front-line chemotherapy entered the study. Patients
received escalated doses of topotecan (starting dose 0.5 mg/m(2)) for 5
days and epirubicin (starting dose 40 mg/m(2)) on day 8, every 28 days.
RESULTS: All patients were assessable for toxicity and 20 for response.
The MTD was topotecan 0.90 mg/m(2) and epirubicin 40 mg/m(2) with
neutropenia being the most common dose-limiting event. Seventy-three
courses were administered. Grade 3-4 neutropenia occurred in 22 (30%)
courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thrombocytopenia in
11 (15%). Seven courses were complicated with fever and one patient died
of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mild and
infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses.
Among 20 patients who were evaluable for response, 16 (80%) were
refractory to prior treatment. One patient with refractory disease (5%)
achieved a complete response of 14 weeks duration and four experienced
stabilization of the disease. CONCLUSIONS: The combination of topotecan
0.90 mg/m(2) on days 1-5, with epirubicin 40 mg/m(2) on day 8,
administered every 28 days is a feasible outpatient regimen which merits
further evaluation in patients with chemosensitive disease.
13
UI - 11557115
AU - Rodriguez-Salas N; Palacios J; Moreno G; de Castro J; Gonzalez-Baron M;
TI -
Gamallo C
Correlation of p53 oncoprotein expression with chemotherapy response in
small cell lung carcinomas.
SO - Lung Cancer 2001 Oct;34(1):67-74
AD - Department of Medical Oncology, Hospital La Paz, Universidad Autonoma de
Madrid, Madrid, Spain.
p53 oncoprotein expression was investigated in small cell lung
carcinomas (SCLC) using immunohistochemical staining with antibodies
against p53. A total of 50 pre-treatment biopsies were examined. We
analyzed the relationship between p53 expression and these patients'
relevant clinical characteristics, response to chemotherapy, time to
progression, and overall survival. We found p53 overexpression in 46% of
the samples but no association with clinical data or overall survival.
Our results show a strong correlation of p53 staining with chemotherapy
response. Multivariate analysis selected p53 as an independent
predictive factor of chemotherapy response.
14
UI - 11562390
AU - Shih JY; Yang SC; Hong TM; Yuan A; Chen JJ; Yu CJ; Chang YL; Lee YC;
TI -
Peck K; Wu CW; Yang PC
Collapsin response mediator protein-1 and the invasion and metastasis of
cancer cells.
SO - J Natl Cancer Inst 2001 Sep 19;93(18):1392-400
AD - Department of Internal Medicine, National Taiwan University Hospital,
Taipei.
BACKGROUND: Numerous genetic changes are associated with metastasis and
invasion of cancer cells. To identify differentially expressed
invasion-associated genes, we screened a panel of lung cancer cell lines
(CL(1-0), CL(1-1), CL(1-5), and CL(1-5)-F(4) in order of increasing
invasive activity) for such genes and selected one gene, collapsin
response mediator protein-1 (CRMP-1), to characterize. METHODS: We used
a microarray containing 9600 gene sequences to assess gene expression in
the cell panel and selected the differentially expressed CRMP-1 gene for
further study. We confirmed the differential expression of CRMP-1 with
northern and western blot analyses. After transfecting and
overexpressing CRMP-1 in highly invasive CL(1-5) cells, the cells were
assessed morphologically and with an in vitro invasion assay. We used
enhanced green fluorescent protein-tagged CRMP-1 and fluorescence
microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80
lung cancer specimens was determined by real-time quantitative reverse
transcription-polymerase chain reaction (RT-PCR). All statistical tests
were two-sided. RESULTS: Expression of CRMP-1 was inversely associated
with invasive activity in the cell panel, an observation confirmed by
northern and western blot analyses. CRMP-1-transfected CL(1-5) cells
became rounded and had fewer filopodia and statistically significantly
lower in vitro invasive activity than untransfected cells (all P< .001).
During interphase, CRMP-1 protein was present uniformly throughout the
cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was
associated with mitotic spindles, centrosomes, and the midbody (in late
telophase). Real-time RT-PCR of lung cancer specimens showed that
reduced expression of CRMP-1 was statistically significantly associated
with advanced disease (stage III or IV; P = .010), lymph node metastasis
(N1, N2, and N3; P =.043), early postoperative relapse (P = .030), and
shorter survival (P = .016). CONCLUSIONS: CRMP-1 appears to be involved
in cancer invasion and metastasis and may be an invasion-suppressor
gene.
15
UI - 11576716
AU - Deppermann KM
TI -
Influence of age and comorbidities on the chemotherapeutic management of
lung cancer.
SO - Lung Cancer 2001 Sep;33 Suppl 1():S115-20
AD - Department of Pneumology, Centre of Lung Diseases and Thoracic Surgery,
Karower Strasse 11, D-13125, Berlin-Buch, Germany. km-deppermann@gmx.de
More than 60% of all patients with cancer are currently older than 65
years. Correspondingly, the peak of lung cancer incidence is reached in
the age group between 75 and 80 years. As a consequence to this ageing
patient population, three factors become of major importance for the
chemotherapeutic management of lung cancer, namely functional status,
age-specific phenomenon and the presence of comorbidities. While the
functional status is dependent on physiological changes in organ
function, ageing-specific phenomena include depression, alterations of
mental status, reduced nutritional status and missing social support.
Comorbidities frequently have a risk profile comparable to that of lung
cancer. Clinical studies with a special focus on elderly patients are
still rare. In small-cell lung cancer retrospective analyses have
demonstrated that age alone is not a major prognostic factor compared to
performance status, tumor stage or gender. Nevertheless elderly patients
with lung cancer are still frequently excluded from clinical trials, and
receive less optimal or even no chemotherapeutic treatment at all.
Studies evaluating less aggressive treatment figured out that single
agent therapy with etoposide is inferior compared to combination
chemotherapy in patients with small cell lung cancer (SCLC). In elderly
patients with non-small cell lung cancer (NSCLC), single agent treatment
with vinorelbine plus 'Best Supportive Care' was significantly superior
to 'Best Supportive Care (BSC)' alone; with respect to survival and
symptom palliation.
16
UI - 11576717
AU - Eberhardt W; Wolf M
TI -
Chemotherapy in stage IV lung cancer (take home messages).
SO - Lung Cancer 2001 Sep;33 Suppl 1():S121-3
AD - Department of Internal Medicine (Cancer Research), University of Essen,
Medical School, Essen Hufelandstrasse 55, D-45122, Essen, Germany.
wilfried.eberhardt@uni-essen.de
17
UI - 11576718
AU - Wolf M
TI -
Dose intensive chemotherapy in small cell lung cancer.
SO - Lung Cancer 2001 Sep;33 Suppl 1():S125-35
AD - Department of Hematology/Oncology, Universitatskliniken Marburg,
Baldingerstrasse, D-35043, Marburg, Germany. wolfm@mailer.uni-marburg.de
The rationale for treatment intensification is to overcome the
occurrence of drug resistance and to improve the outcome in SCLC.
Several different approaches have been tested in the past two decades.
Increasing the dose of conventional chemotherapy has failed to improve
survival in extensive stage. In limited stage patients one randomized
trial demonstrated a significant survival advantage by a 20% increase of
the dose of cisplatin and cyclophosphamide given during the first cycle
of chemotherapy. Shortening treatment intervals is achievable by weekly
chemotherapy or by use of hematopoietic growth factors. Neither weekly
chemotherapy, tested in four randomized trials, nor the application of
hematopoietic growth factors significantly improved survival. However,
two studies described a better survival for patients receiving
chemotherapy in shorter treatment intervals. In one trial a 3-week
interval was superior to a 4-week interval, and in a second one a 2-week
interval superior to a 3-week interval. One smaller study, comparing a
4-week interval with a 2-week interval with stem cell augmentation by
whole blood, revealed no difference in survival between both groups. A
randomized trial comparing chemotherapy in intervals as short as
possible with or without growth factor application showed no difference
for the two groups. Thus, growth factor application seems not to be
essential for treatment in short intervals and was not associated with
superior survival in randomized trials. To achieve a more than two-fold
increase in dose intensity some kind of stem cell support is mandatory.
Several phase II trials with small patient numbers tested the concept of
late intensification with bone marrow support in the 1980s. These trials
did not show any convincing benefit. There is one randomized trial
available testing the late intensification approach in which a superior
progression free survival and a trend for better survival was
demonstrated, but this difference was not statistically significant due
to a high mortality rate and a substantial number of local relapses in
the high dose arm. Newer concepts involving high dose therapy are
combining high dose strategies with approaches for better local tumor
control, administer high dose regimens earlier in the treatment course,
or use multiple sequential high dose cycles. With these approaches
3-year survival rates of up to 40% have been reported. So up to date,
the superiority of an intensified treatment strategy has not been
demonstrated in a convincing way and further controlled trials will be
necessary to clarify the role of dose intense chemotherapy in SCLC.
18
UI - 11576719
AU - Dunst J
TI -
Role of radiotherapy in small cell lung cancer.
SO - Lung Cancer 2001 Sep;33 Suppl 1():S137-41
AD - Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg,
Dryanderstrasse 4, D-06097, Halle, Germany.
juergen.dunst@medizin.uni-halle.de
Traditionally, small cell lung cancer has been considered as a disease
with early onset of distant metastases. Therefore, the role of
locoregional therapy (radiotherapy or surgery) was thought to be very
limited. This was supported by the first trials investigating the role
of radiotherapy since there was no improvement of median survival.
Recently, two meta-analyses changed this point of view: radiotherapy is
essential to achieve long term survival. The possible biological
explanation may be that uncontrolled distant metastases may cause the
death of patients during the first months of their disease. The longer
patients survive the more important local therapy becomes. Today, there
is growing acceptance that adequate systemic and local therapy
contributes to better treatment results of limited small cell lung
cancer.
19
UI - 11576720
AU - Wendt TG
TI -
Thoracic radiotherapy in the treatment of limited disease of small-cell
cancer: sequence and fractionation.
SO - Lung Cancer 2001 Sep;33 Suppl 1():S143-6
AD - Department of Radiation Oncology, Friedrich-Schiller-University,
Bachstrasse 18, D-07743, Jena, Germany. thomas.wendt@med.uni-jena.de
Since two meta-analyses showed improved survival rates at 3 years of
approximately 5%, thoracic radiotherapy is accepted as an essential
component of optimal management of limited-disease. However, optimal
sequencing, timing, fractionation, dose, and field size still remain a
matter of controversy. The issue has changed since the traditional
doxorubicin-based chemotherapy has been substituted by cisplatin based
regimens which clearly produce less acute toxicity and allow concomitant
chemoradiation protocols. Up-front radiotherapy seems to improve 5-years
survival rates compared to the traditional sequential modality.
Different fractionation schedules and escalated total doses are tested
prospectively in order to reduce the intrathoracic relapse rate.
Increased intensity of intrathoracic radiotherapy seems to augment long
term survival rates.
20
UI - 11576721
AU - Passlick B
TI -
Can surgery improve local control in small cell lung cancer?
SO - Lung Cancer 2001 Sep;33 Suppl 1():S147-51
AD - Department of Thoracic Surgery, Asklepios-Fachkliniken Munchen-Gauting,
Klinik fur Thoraxchirurgie, Robert-Koch-Allee 2, D-82131, Gauting,
Germany. passlick@lrz.uni-muenchen.de
Current therapy for small cell lung cancer (SCLC) consists of
chemotherapy with or without radiotherapy. Radiotherapy is generally
accepted as an essential treatment component of limited stage disease.
However, the local failure rate after chemo- and radiotherapy is still
high and ranges from 30 to 70%. Furthermore, despite having obtained a
complete radiographic response, up to 75% of these patients will have
residual disease in the tumor specimen, if resection is performed.
Therefore, more effective means are needed to eradicate the primary
tumor and to obtain an improved local disease control. Recent phase two
trials of multimodal regimens for stage I-IIIA SCLC demonstrate that in
selected patients with early stage SCLC the combination of surgery and
chemotherapy with or without radiotherapy is feasible with low morbidity
and mortality rates. The combination therapy results in satisfying long
term outcome depending on the pathological tumor stage and a local
disease control is achieved in almost all patients. It is remarkable
that the pneumonectomy rate has decreased over the past decades from
almost 100 to 27-39%. In order to confirm these promising results, a
German multicenter prospective randomized phase III trial has been
designed for patients with stage I-IIIA SCLC consisting of induction
chemotherapy, followed by surgery, adjuvant thoracic radiotherapy and
prophylactic cranial radiation compared to thoracic radiotherapy and
prophylactic cranial radiation.
21
UI - 11576723
AU - Passlick B; Fietkau R
TI -
Therapy of small cell lung cancer without distant metastases (take home
messages).
SO - Lung Cancer 2001 Sep;33 Suppl 1():S159-61
AD - Department of Thoracic Surgery, Aesklepios-Fachkliniken Munchen-Gauting,
Klinik fur Thoraxchirurgie, Robert-Koch-Allee 2, D-82131, Gauting,
Germany. passlick@lrz.uni-muenchen.de
22
UI - 11576714
AU - Schuette W
TI -
Chemotherapy as treatment of primary and recurrent small cell lung
cancer.
SO - Lung Cancer 2001 Sep;33 Suppl 1():S99-107
AD - Second Medical Department, City Hospital Martha Maria Halle-Dolau,
Rontgenstrasse 1, D-06120, Halle, Germany.
wolfgang.schuette@medizin.uni-halle.de
Chemotherapy is the treatment of choice in metastatic stage of
small-cell lung cancer (SCLC). Radiation therapy, surgery and other
forms of therapy are only included in special treatment situations,
particularly for different local problems. A wide range of
chemotherapeutic agents have proven to be effective in SCLC, including
carboplatin, cisplatin, cyclophosphamide, doxorubicin, epirubicin,
etoposide, ifosfamide, teniposide and vincristine. However, treatment
results could not be improved over the last 10 years and the median
survival of patients with metastatic disease is limited to 7-10 months.
New agents like docetaxel, gemcitabine, irinotecan, paclitaxel,
topotecan and vinorelbine have shown promising results in phase-II
investigations. Yet, no evidence is provided from randomized trials to
employ these drugs in first line treatment. Clearly, polychemotherapy is
superior to single agent treatment. Compared to the combination of
cisplatin and etoposide, no other combination has clearly shown improved
results in large phase-III randomised trials, yet. The combination of
cisplatin and irinotecan has also shown promising results in a single
randomised trial with the need to be confirmed in larger settings.
Neither extending the initial treatment beyond the median number of six
cycles, nor maintenance treatment have-so far-resulted in any increase
in survival results for patients with metastasised SCLC. Nor has
dose-intensification, which causes significantly higher toxicities in
patients, shown a clear impact on the overall survival of these
patients. Brain metastases represent a high frequent complication
associated with SCLC. In these cases, the combination of chemotherapy
and whole brain radiation therapy is advocated. Second-line treatment
should always be considered in patients with relapse or failure to
first-line therapy. In addition to a rechallenging with the prior drug
combination or selecting a different potentially non-cross resistant
one, monotherapy with topotecan proved to be effective as well. In
summary, up to now, no standard chemotherapy combination exists for
metastatic SCLC. The individual therapy strategy can only be selected by
considering the clinically relevant conditions of the patient.
23
UI - 11593634
AU - Zhang D; Zhang R; Cheng G
TI -
The surgical treatment of lung cancer: a retrospective analysis of 2004
cases.
SO - Chin Med J (Engl) 1999 Jan;112(1):25-8
AD - Department of Thoracic Surgery, Cancer Institute/Hospital, Chinese
Academy of Medical Sciences, Beijing 100021, China.
tsch@public.bta.net.cn
OBJECTIVE: To summarise the clinical results of surgical treatment of
2004 cases of lung cancer over a period of 33 years and to evaluate the
main influencing factors for long-term results. METHODS: 2004 patients
treated at our department were included in this study. The pathological
classification proposed and revised by WHO in 1982 was used. The TNM
(tumour, nodes, and metastasis classification) system of staging
proposed and modified by UICC (International Union Against Cancer) in
1987 was followed. Pearson's Chi-square test was used in comparing
variables. RESULTS: There were 1571 men and 433 women, with a man to
woman ratio of 3.6:1. The pathological findings were squamous cell
carcinoma (944 cases, 47.1%), adenocarcinoma (694, 34.6%), small cell
carcinoma (167, 8.3%), adenosquamous cell carcinoma (78, 3.9%), large
cell carcinoma (22, 1.1%), alveolar cell carcinoma (17, 0.8%) and
miscellaneous carcinoma (82, 4.1%). The p-TNM staging in 1721 resected
cases was: stage 0 (2 cases, 0.1%), stage I (860, 50%), stage II (407,
23.6%), staging IIIa (396, 23.0%), stage IIIb (35, 2.0%) and stage IV
(21, 1.2%). The overall resection rate was 85.9% (1721/2004) and the
complication rate was 15.7% (271/1721). The 30-day mortality was 1.3%
(22/1721). The 5-, 10- and 15-year survival rates were 38.8%, 31.6% and
21.8%, respectively. Factors influencing the long-term survival rate
included the nature of resection, the mode of resection, presence or
absence of lymph gland metastasis, tumour size and degree of extension,
pathological type and p-TNM staging. CONCLUSIONS: Surgery is recommended
for stage I, II and IIIa non-small cell lung cancer and for stage I and
II small cell lung cancer. Meticulous preoperative staging process is
important. Bronchoplastic resection is recommended to replace
pneumonectomy whenever the conditions are permissible.
24
UI - 11680466
AU - Arriagada R; Pignon JP; Le Chevalier T
TI -
Initial chemotherapeutic doses and long-term survival in limited
small-cell lung cancer.
SO - N Engl J Med 2001 Oct 25;345(17):1281-2
25
UI - 11598408
AU - Schiller JH
TI -
Novel therapies in lung cancer management. An update on the role of
topotecan.
SO - Oncology 2001;61 Suppl 1():1-2
AD - University of Wisconsin Hospital, Madison, 53792, USA.
jhschill@facstaff.wisc.edu
26
UI - 11598410
AU - Huang CH; Treat J
TI -
New advances in lung cancer chemotherapy: topotecan and the role of
topoisomerase I inhibitors.
SO - Oncology 2001;61 Suppl 1():14-24
AD - Fox Chase-Temple Cancer Center, Philadelphia, PA 19140, USA.
Objective tumor responses and survival rates with standard chemotherapy
options for small-cell lung cancer (SCLC) and non-small-cell lung cancer
(NSCLC) have been disappointing. However, several promising new classes
of agents have emerged in recent years, including the taxanes, mitotic
spindle inhibitors, antimetabolites, and topoisomerase I and II
inhibitors. The molecular target of several of these new agents is
topoisomerase I, an enzyme that is essential for DNA replication and is
up-regulated in tumor cells. Inhibition of this enzyme by drugs such as
topotecan and irinotecan leads to cell death and is the basis for their
anticancer activity. The process of DNA replication is halted by the
covalent binding of the drug in a topoisomerase I drug/DNA ternary
reaction intermediate. The pharmacokinetics of the approved regimen--a
30-min infusion daily for 5 days at 21-day intervals--are well defined,
with proportional increases in the area under the plasma
concentration-time curve, peak plasma concentration, and steady state
concentration following application of higher doses. The antitumor
activities of both the intravenous and oral formulations of topotecan
have been tested in clinical trials. Topotecan is well tolerated and has
demonstrated good efficacy in patients with relapsed SCLC when
administered as monotherapy or in combination regimens as first-line or
second-line therapy. Preliminary trials also indicate that topotecan is
well tolerated and has activity in the first-line treatment of NSCLC. In
this article an overview of new agents in lung cancer chemotherapy is
provided, with particular attention paid to the topoisomerase I
inhibitors. A review of topotecan--the first topoisomerase I inhibitor
to be approved for second-line therapy in SCLC--is presented as an
illustration of the promise these new agents hold for the treatment of
SCLC and NSCLC. Copyright 2001 S. Karger AG, Basel
27
UI - 11598411
AU - O'Neill P; Clark PI; Smith D; Marshall E; Hannigan K; Ross G
TI -
A phase I trial of a 5-day schedule of intravenous topotecan and
etoposide in previously untreated patients with small-cell lung cancer.
SO - Oncology 2001;61 Suppl 1():25-9
AD - Department of Medical Oncology, Clatterbridge Centre of Oncology,
Bebington, Wirral, Merseyside, UK.
A phase I dose-escalation study was undertaken to determine the maximum
tolerated dose of the intravenous combination of topotecan and etoposide
in previously
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