Table of Contents
1
UI - 11437416
AU - Farrugia D; Lewis R
TI -
Chemotherapy and quality of life in advanced NSCLC.
SO - Br J Cancer 2001 Jul 6;85(1):137-8
2
UI - 11740990
AU - Waller DA
TI -
Neoadjuvant chemotherapy in non small cell lung cancer-the UK
experience.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S31-3
AD - Glenfield Hospital, Leicester LE3 9QP, UK. debra.grew@uhl-tr.nhs.uk
3
UI - 11740991
AU - Sutedja G; Postmus PE
TI -
The role of photodynamic therapy in the management of stage I/II NSCLC.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S35-8
AD - Department of Pulmonology, Academic Hospital Vrije Universiteit, P.O.
Box 7057, 1007 Mb, Amsterdam, The Netherlands. tg.sutedja@azvu.nl
There is a resurgence of interest in lung cancer screening, motivated by
the fact that many lung cancer patients cannot be cured due to advanced
disease at presentation. Lung cancer screening may detect more early
stage disease. Very early stage squamous cell type lung cancer in the
central tracheobronchial tree can be detected and local bronchoscopic
treatments such as photodynamic therapy can be applied if the tumor is
strictly intraluminal and nodal disease is absent. So, accurate staging
regarding tumor size and nodal disease is much more important than
treatment per se. Bronchoscopic treatments are less morbid treatment
alternatives than surgery and surgical bronchoplasty, especially for
patients suffering from COPD and who have poor cardiovascular status due
to their smoking history.
4
UI - 11740994
AU - Kris MG; Azzoli CG
TI -
Chemotherapy for early stage non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S49-52
AD - Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275
York Avenue, New York, NY 10021, USA. krism@mskcc.org
For patients with locally advanced non-small cell lung cancer (NSCLC)
undergoing surgery, both induction and adjuvant chemotherapy improve
survival and curability. Induction chemotherapy is also feasible for
patients with early stage NSCLC. Randomized trials of induction
treatment for early stage NSCLC, as well as induction and adjuvant
treatment for Stage IIIA patients, are in progress. These trials should
build on current successes, and add new approaches such as targeted
therapies and vaccines, in an attempt to prevent metastases, recurrence,
and second primary malignancies.
5
UI - 11740995
AU - Manegold C
TI -
Chemotherapy in Stage I/II NSCLC and projects of the EORTC-Lung Cancer
Group for Early Stage Lung Cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S53-8
AD - Thoraxklinik-Heidelberg gGmbH, Amalienstrasse 5, 69126 Heidelberg,
Germany. prof.manegold@t-online.de
The utilization of systemic chemotherapy within multi-modality treatment
concepts in early stage NSCLC would seem to be a very promising concept,
which potentially could lead to increased survival rates. It must be
noted, however, that application of multi-modality treatment strategies
in Stage I and II NSCLC is still experimental and should only be applied
within clinical trials. Caution is thus advisable because the existing
data are not conclusive and there still are a great number of questions
to be answered concerning at least: (1) the regimen, the intensity, the
duration of therapy and the most appropriate schedule to be used for
chemotherapy, (2) the most appropriate time for surgery and its
extensiveness, and (3) the time, dose, and best application modus for
radiotherapy. The Lung Cancer Group of the EORTC has been active in the
clinical development of multi-modality treatment strategies to improve
treatment results for patients with localized, early NSCLC and presently
offers its members several attractive studies dealing with induction
preoperative chemotherapy, induction preoperative chemo-radiotherapy,
and sequential/concomitant chemo-radiotherapy.
6
UI - 11740996
AU - Novello S; Le Chevalier T
TI -
Ongoing/planned studies in France Stage I-II NSCLC.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S59-61
AD - Department of Medicine, Institut Gustave-Roussy, Rue Camille-Desmoulins,
94805 Villejuif Cedex, France.
7
UI - 11740997
AU - Rosell R; Felip E; Maestre J; Sanchez JM; Sanchez JJ; Manzano JL;
TI -
Astudillo J; Taron M; Monzo M
The role of chemotherapy in early non-small-cell lung cancer management.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S63-74
AD - Medical Oncology Service, Hospital Germans Trias i Pujol, Ctra Canyet,
s/n, 08916 Badalona (Barcelona), Spain. rrosell@ns.hugtip.sc.es
Great advances have been made in chemotherapy in advanced and metastatic
non-small-cell lung cancer (NSCLC), and a major milestone was reached
with the administration of neoadjuvant chemotherapy in stage IIIA N2
disease. The systemic nature of lung cancer has been confirmed by many
genetic analyses documenting micrometastases in negative lymph nodes and
bone marrow, and mRNA gene overexpression as a surrogate of cancer cells
has been identified in peripheral blood. Furthermore, serum or plasma
cell-free tumor DNA has been observed even in tumors with a diameter of
less than 2 cm. Pharmacogenetic screening can lead to tailored
chemotherapy even in patients with early disease through the use of a
genetic tool kit that will allow us to optimize the use of chemotherapy
by using serial measurements of serum DNA that can help to detect
residual disease and re-assess the chemosensitivity of sub-clinical
micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin
hope (NATCH) trial is testing the value of three cycles of chemotherapy
given pre- or post-operatively compared with surgery alone and will
analyze genetic abnormalities in serum DNA at three different points
during patient follow-up. Our major concern in this review is to analyze
the pros and cons of chemotherapy in NSCLC. Although this review is not
a formal meta-analysis, we have discussed the most relevant published
studies in this field. We conclude that not only is there no evidence of
detrimental effects of chemotherapy, in fact, there are many indications
that chemotherapy induces response in up to 80% of patients and
downgrades N2 disease in up to 50% of patients. This translates into
significantly better survival when accompanied by complete resection.
Since at least 50% of patients with stage IB disease develop distant
metastases, it seems logical to explore the role of chemotherapy in
early disease.
8
UI - 11740999
AU - Shepherd FA
TI -
Angiogenesis inhibitors in the treatment of lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S81-9
AD - Division of Medical Oncology, Department of Medicine, Princess Margaret
Hospital, 610 University Avenue, 5-104, University of Toronto, Ont.,
Toronto, Canada, M5G 2M9. frances.shepard@uhn.on.ca
Numerous inhibitors of angiogenesis are currently under study in lung
cancer. Four trials of adjuvant interferon after chemotherapy for small
cell lung cancer (SCLC) were negative. Several metalloproteinase
inhibitors (MMPIs) are now in study in SCLC and non-small cell lung
cancer (NSCLC). Two large randomized trials have closed recently in
which Marimastat 10 mg bid was compared to placebo in responding
patients with SCLC. Two randomized studies of Prinomastat versus placebo
with combination chemotherapy in advanced NSCLC have also completed
accrual. The results of these trials are not yet available, but should
be reported in mid-2001. A Phase III trial of BMS-275291, a
broad-spectrum MMPI in combination with paclitaxel and carboplatin is
open for patients with advanced NSCLC. Neovastat, a standardized shark
cartilage extract is under study in inoperable Stage III NSCLC. VEG-F
gene expression is increased in many tumors including NSCLC, and may act
as a paracrine mediator of growth. A randomized Phase II trial of
paclitaxel and carboplatin with or without a recombinant humanized
anti-VEG-F has been undertaken in NSCLC. Modestly better response and
survival were seen with anti-VEG-F and a large Phase III trial is
planned. Numerous receptor tyrosine kinases (TK) have been found to be
directly or indirectly involved in angiogenesis including Flk-1, Flt-l,
Tie-1 and Tie-2. SU5416 is a small molecular TK inhibitor and potent
inhibitor of VEG-F-mediated Flk-1 receptor signaling. Another TK
inhibitor SU6668 blocks VEG-F, bFGF and PDGF receptor signaling. It is
orally available, and it may be evaluated in lung cancer trials in the
near future. ZD4190 is an inhibitor of KDR/Flk-1 that may be evaluated
in SCLC. Thalidomide has recently been shown in pre-clinical models to
be anti-angiogenic. A randomized trial of paclitaxel/carboplatin and
radiation with or without thalidomide is open for patients with Stage
IIIB NSCLC in the United States. Numerous other anti-angiogenesis agents
are in early clinical trials, but have not been evaluated in lung cancer
yet.
9
UI - 11803144
AU - Turrisi AT; Sherman CA
TI -
The treatment of limited small cell lung cancer: a report of the
progress made and future prospects.
SO - Eur J Cancer 2002 Jan;38(2):279-91
AD - Department of Radiation Oncology, Medical University of South Carolina,
169 Ashley Avenue, POB 250318, Charleston, SC 29425, USA.
turrisi@radonc.musc.edu
The improvements in the treatment of small cell lung cancer over the
last 30 years have been realised by understanding that it is a systemic
disease, but that areas of bulk and sanctuary require a complementary
therapy. Despite successful strategies using combinations and thoracic
radiotherapy, there remains uncertainty about what the best regimens
are, their timing and their intensity. However, earlier concurrent
therapy and rather brief intense chemotherapy and radiotherapy seem to
produce the best results in moderately fit patients of all ages. How to
select the fit patients and what to do about the less fit ones remains
controversial and have economic consequences for governments and payers.
Despite a meta-analysis demonstrating the success of prophylactic
cranial irradiation (PCI), doubts linger about its safety, despite
nothing more than anecdotal evidence from a previous era. The role of
surgery continues to be explored, more in Europe than North America or
Asia. Strategies for treatment of minimum residual disease seem a focus.
New drugs, molecular targeted therapy, immunotherapy and other molecular
therapies offer promise and theory, but there is little evidence about
their place in the treatment protocols of today.
10
UI - 11894020
AU - Gandara DR; Lara PN Jr; Goldberg Z; Le QT; Mack PC; Lau DH; Gumerlock PH
TI -
Tirapazamine: prototype for a novel class of therapeutic agents
targeting tumor hypoxia.
SO - Semin Oncol 2002 Feb;29(1 Suppl 4):102-9
AD - Division of Hematology-Oncology and the Department of Radiation
Oncology, University of California, Sacramento, CA 95817, USA.
Preclinical models in vitro and in vivo have shown that tumor hypoxia
alters the malignant cell phenotype, selecting for p53 mutations,
stimulating angiogenesis and metastasis, and markedly reducing the
efficacy of both radiotherapy and chemotherapy. Similarly, clinical
studies measuring pretreatment tumor oxygen status confirm that the
presence of hypoxia confers a negative impact on local control,
disease-free survival, and overall survival. Despite these data and
extensive past research efforts, the promise of developing selective
hypoxic-cell sensitizers has been largely unfulfilled. In contrast,
tirapazamine is the rationally designed prototype for a new class of
therapeutic agents targeting tumor hypoxia: hypoxic cytotoxins.
Tirapazamine is bioreductively activated in hypoxic cells and has been
shown to potentiate the cytotoxicity of radiation and a number of
chemotherapeutic drug classes, in particular platinum compounds and
taxanes. This article reviews the preclinical and clinical development
of tirapazamine, as well as current trials in non-small cell lung cancer
designed to provide proof of principle for this new category of cancer
therapeutics.
11
UI - 11894021
AU - Rosell R; Monzo M; Alberola V; Taron M; Barnadas A; Sanchez JM; Manzano
TI -
JL; Sanchez JJ
Determinants of response and resistance to cytotoxics.
SO - Semin Oncol 2002 Feb;29(1 Suppl 4):110-8
AD - Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona,
Spain.
There is an underlying feeling in the oncology community that
chemotherapy has reached a therapeutic "glass ceiling" in non-small cell
lung cancer, and that we will never attain the acceptable survival rates
that are just beyond our reach. Multiple clinical trials have tested
doublets, triplets, and sequential chemotherapy in what is often
regarded as a futile attempt to break through this ceiling. Recent large
randomized trials have not shown that any of these combinations is
superior to any of the others. Nevertheless, the analysis of DNA and RNA
from patients' serum can permit us to assess genes that may be specific
targets of certain cytotoxic agents and others that may be markers of
multidrug resistance. With this information, we will hopefully be able
to create guidelines for individualized chemotherapy. With this in mind,
the Spanish Lung Cancer Group has designed a trial to test the
involvement of various genes in resistance to gemcitabine and cisplatin.
With the gene corral that will emerge from this trial, we will create an
up-front diagnostic test for selecting the most appropriate gemcitabine
plus cisplatin regimen for the treatment of non-small cell lung cancer.
12
UI - 11894010
AU - Arteaga CL; Khuri F; Krystal G; Sebti S
TI -
Overview of rationale and clinical trials with signal transduction
inhibitors in lung cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 4):15-26
AD - Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt
University School of Medicine, Nashville, TN 37232-6307, USA.
Most cellular proto-oncogenes encode proteins that participate in
signaling pathways by which cells receive and execute instructions that
lead to mitogenesis, differentiation, lineage determination, cell
migration, extracellular matrix production, and apoptosis, among others.
These proto-oncogene protein products include transmembrane receptor
tyrosine kinases and receptor substrates, serine/threonine kinases,
receptor adaptor molecules, low-molecular-weight GTPases, and
transcription factors that, when overexpressed or mutationally
activated, can lead to cell transformation and tumor progression. The
large number of oncogenic protein tyrosine kinases plus the rare
presence of phosphotyrosine in nontransformed cells argue persuasively
that tyrosine phosphorylation and activation of signaling molecules
downstream from receptor tyrosine kinases are critical events in growth
control and transformation and are, therefore, rational targets for
anticancer molecular therapies. We will review some of the more recent
treatment strategies in non-small cell and small cell lung cancer
targeted to dysregulated signaling pathways that are causally associated
with tumor maintenance and progression.
13
UI - 11894015
AU - Azzoli CG; Krug LM; Miller VA; Kris MG; Mass R
TI -
Trastuzumab in the treatment of non-small cell lung cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 4):59-65
AD - Department of Thoracic Oncology Service, Memorial Sloan-Kettering Cancer
Center, New York, NY 10021, USA.
Trastuzumab is a humanized monoclonal antibody that binds to human
epidermal growth factor-2 (HER2) and is approved by the US Food and Drug
Administration for the treatment of advanced breast cancer that
overexpresses HER2/neu protein. Preclinical data suggests a role for
trastuzumab in the treatment of non-small cell lung cancer (NSCLC). HER2
protein is overexpressed in 20% to 66% of resected NSCLC tumors, and has
been shown to predict poor patient outcome in multiple series.
Experiments with NSCLC cell lines show that HER2 overexpression
increases chemoresistance, invasiveness, and metastatic potential of the
cells. In mouse xenograft experiments, trastuzumab halts tumor growth
and is synergistic with cytotoxic chemotherapy. Ongoing phase II trials
are showing that trastuzumab can be added to standard chemotherapy in
the treatment of patients with advanced NSCLC without additional
toxicity, and with promising efficacy. Whether trastuzumab will show a
clear benefit for patients with NSCLC, either alone or in combination
with established chemotherapy, remains to be proven in phase III
testing.
14
UI - 11894017
AU - Bonomi P
TI -
Matrix metalloproteinases and matrix metalloproteinase inhibitors in
lung cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 4):78-86
AD - Department of Medical Oncology, Rush Cancer Institute, Chicago IL
60612-3824, USA.
Preclinical studies have provided evidence that matrix
metalloproteinases (MMPs), a family of zinc-containing proteolytic
enzymes, facilitate tumor invasion, the establishment of metastases, and
the promotion of tumor-related angiogenesis. Matrix metalloproteinase
inhibitors (MMPIs) have been shown to inhibit tumor growth and
dissemination in preclinical models. Not all lung cancers express the
MMPs believed to be most important in promoting the neoplastic process,
and there are conflicting reports regarding the prognostic significance
of MMPs in lung cancer. However, it is possible that these observations
are because of limitations in the procedures for measuring MMPs. Many
investigators believe that MMPs are universally involved in tumor
progression; this hypothesis was the basis for initiating seven phase
III MMPI trials in lung cancer. Four studies were closed at completion
of the predefined accrual goal, and three were closed early. There were
no significant differences in survival in a non-small cell lung cancer
prinomastat study, and in a small cell lung cancer marimastat trial. The
results of the remaining five studies have not been reported. At this
point it appears that MMPIs will probably not play a major role in the
treatment of advanced lung cancer patients.
15
UI - 11915730
AU - Mori K; Kamiyama Y; Kondoh T; Tominaga K
TI -
[Phase II study of combined Vinorelbine (Navelbine) plus cisplatin for
advanced non-small cell lung cancer (an interim report)]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):405-10
AD - Dept. of Thoracic Diseases, Tochigi Cancer Center.
A phase II study of a combination therapy with vinorelbine (Navelbine)
plus cisplatin was performed using 27 patients with advanced non-small
cell lung cancer, to evaluate the efficacy and safety of this therapy.
Patients were treated, at 3-week intervals, with two or more courses of
a regimen consisting of vinorelbine 25 mg/m2 (days 1, 8) and cisplatin
80 mg/m2 (day 1). The response rate was 48.1% (13/27) (95% confidence
interval: 28.7-68.1%). The median number of treatment courses was 2.6.
The major toxicity was hematological: 74% of patients had neutropenia of
grade 3 or higher that subsided rapidly upon administration of a
granulocyte-colony stimulating factor. Non-hematological toxicities were
mild, of grade 2 or less: the main symptom was nausea/vomiting (62%),
although constipation, eruption, anorexia, peripheral nerve disorders,
diarrhea, fever, and other conditions were also observed. In conclusion,
the high response rate and good tolerance to this combination therapy
warrants further study.
16
UI - 11891611
AU - Shiau YC; Tsai SC; Wang JJ; Ho YJ; Ho ST; Kao CH
TI -
Technetium-99m tetrofosmin chest imaging related to p-glycoprotein
expression for predicting the response with paclitaxel-based
chemotherapy for non-small cell lung cancer.
SO - Lung 2001;179(4):197-207
AD - Department of Nuclear Medicine, Far Eastern Memorial Hospital, Institute
of Biomedical Engineering, College of Electrical Engineering, National
Taiwan University, Taipei, Taiwan.
Our aim was to use technetium-99m tetrofosmin (Tc-TF) uptake in
non-small cell lung cancer (NSCLC) for predicting the chemotherapeutic
response of NSCLC to paclitaxel and to compare the results with the
expression of multidrug resistance (MDR) - P-glycoprotein (Pgp). Twenty
patients with advanced NSCLC were enrolled in this study before
chemotherapy with paclitaxel. Tc-TF chest imaging was performed to
calculate early and delayed tumor-to-normal lung (T/NL) count-density
ratios, as well as washout indexes (WIs). Immunohistochemical analyses
were performed on multiple nonconsecutive sections of the biopsy
specimens to detect Pgp expression. The response to chemotherapy was
evaluated by clinical and radiological methods in the third month after
completion of treatment. The early and delayed T/NL count-density ratios
of patients with good response were significantly higher than those of
patients with poor response (p <0.05). However, no significant
difference in WI between the two groups of patients was found (p >
0.05). A significantly higher incidence of good response was found in
patients with negative Pgp expression (100%) than in patients with
positive Pgp expression (40%) (p <0.05). Significantly higher early and
delayed T/NL count-density ratios as well as decreased WIs were found in
patients with negative Pgp expression than in patients with positive Pgp
expression. However, other prognostic factors (age, sex, body weight
loss, performance status, tumor stage, and tumor cell type) were not
significantly different between the patients with good response and
those with poor response. Because Tc-TF chest images can correctly
represent the expression of Pgp in NSCLC, it can accurately predict the
chemotherapeutic response to paclitaxel.
17
UI - 11870177
AU - Socinski MA; Schell MJ; Peterman A; Bakri K; Yates S; Gitten R; Unger P;
TI -
Lee J; Lee JH; Tynan M; Moore M; Kies MS
Phase III trial comparing a defined duration of therapy versus
continuous therapy followed by second-line therapy in advanced-stage
IIIB/IV non-small-cell lung cancer.
SO - J Clin Oncol 2002 Mar 1;20(5):1335-43
AD - Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive
Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
socinski@med.unc.edu
PURPOSE: To compare four cycles of therapy versus continuous therapy to
determine the optimal duration of chemotherapy in advanced
non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB/IV
NSCLC patients were randomized to arm A (four cycles of carboplatin at
an area under the curve of 6 and paclitaxel 200 mg/m(2) every 21 days)
or arm B (continuous treatment with carboplatin/paclitaxel until
progression). At progression, all patients on both arms were to receive
second-line weekly paclitaxel at 80 mg/m(2)/wk. The primary end points
were survival and quality of life (QOL). RESULTS: Two hundred thirty
patients were randomized. Fifty-seven percent of arm A patients
completed four courses of therapy. In the 116 arm B patients, the median
number of cycles delivered was four (range, zero to 19 cycles).
Forty-two percent received five or more cycles; 18% received eight or
more cycles. Overall response rates were 22% and 24% for arms A and B,
respectively (P =.80). Median survival time and 1-year survival rates
were 6.6 months and 28% for arm A and 8.5 months and 34% for arm B,
respectively (log-rank P =.63). Rates of hematologic and nonhematologic
toxicity were similar between the two arms, except for neuropathy. The
rate of grade 2 to 4 neuropathy increased from 19.9% (95% confidence
interval [CI], 13.6% to 26.2%) at cycle 4 to 43% (95% CI, 28.6% to
57.4%) at cycle 8. There were no differences in QOL. Only 45% of
patients received second-line therapy (42% in arm A v 47% in arm B, P
=.42). CONCLUSION: This study shows no overall benefit in survival,
response rates, or QOL to continuing treatment with
carboplatin/paclitaxel beyond four cycles in advanced NSCLC.
18
UI - 11762805
AU - Tjan-Heijnen VC; Postmus PE; Ardizzoni A; Manegold CH; Burghouts J; van
TI -
Meerbeeck J; Gans S; Mollers M; Buchholz E; Biesma B; Legrand C;
Debruyne C; Giaccone G; European Organisation for Research and Treatment
of Cancer-Lung Cancer Group
Reduction of chemotherapy-induced febrile leucopenia by prophylactic use
of ciprofloxacin and roxithromycin in small-cell lung cancer patients:
an EORTC double-blind placebo-controlled phase III study.
SO - Ann Oncol 2001 Oct;12(10):1359-68
AD - Department of Medical Oncology, University Medical Center Nijmegen,The
Netherlands. V.Tjan@onco.azn.nl
BACKGROUND: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the
standard chemotherapy regimens in the treatment of small-cell lung
cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this
trial the impact of prophylactic antibiotics on incidence of febrile
leucopenia (FL) during chemotherapy for SCLC was evaluated. PATIENTS AND
METHODS: Patients with chemo-naive SCLC were randomized to standard-dose
CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v.,
q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks,
x4, with filgrastim 5 microg/kg/day days 4-13) to assess the impact on
survival (n = 240 patients). Patients were also randomized to
prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150
mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163
patients). This manuscript focuses on the antibiotics question. RESULTS:
The incidence of FL during the first cycle was 25% of patients in the
placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an
overall incidence through all cycles of 43% vs. 24% respectively (P =
0.007; 1-sided). There were less Gram-positive (12 vs. 4), Gram-negative
(20 vs. 5) and clinically documented (38 vs. 15) infections in the
antibiotics arm. The use of therapeutic antibiotics was reduced (P =
0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17
patients, P = 0.013: 1-sided). However, the overall number of days of
hospitalization was not reduced (P = 0.05; 1-sided). The number of
infectious deaths was nil in the antibiotics vs. five (6%) in the
placebo arm (P = 0.022; 2-sided). CONCLUSIONS: Prophylactic
ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the
incidence of FL, the number of infections, the use of therapeutic
antibiotics and hospitalizations due to FL by approximately 50%, with
reduced number of infectious deaths. For patients with similar risk for
FL, the prophylactic use of antibiotics should be considered.
19
UI - 11762806
AU - Feliu J; Martin G; Lizon J; Chacon JI; Dorta J; de Castro J; Rodriguez
TI -
A; Sanchez Heras B; Torrego JC; Espinosa E; Gonzalez Baron M; Oncopaz
Cooperative Group, Spain
Sequential therapy in advanced non-small-cell lung cancer with weekly
paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II
study.
SO - Ann Oncol 2001 Oct;12(10):1369-74
AD - Servicio de Oncologia Medica, Hospitals La Paz, Madrid, Spain.
oncopaz@ene.es
OBJECTIVES: New effective therapies are needed to improve the outcome of
patients with advanced non-small-cell lung cancer (NSCLC). The aim of
this study was to assess the response rate and survival obtained with a
sequential regimen of chemotherapy. PATIENTS AND METHODS: Patients with
newly diagnosed stage IIIb-IV NSCLC were included. They all had
measurable disease and a good performance status (0-2 in the Eastern
Cooperative Oncology Group scale). Chemotherapy consisted of weekly
paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100
mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and
vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every
28 days for a maximum of six courses. RESULTS: Fifty-two patients were
included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease.
After therapy with weekly paclitaxel. 29 partial responses were obtained
(56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients
had stable disease (29%) and eight had a progression (15%). After CGV,
there were four complete remissions (8%) and 24 partial responses (46%),
for an overall response rate of 54% (95% CI: 37%-65%). Eight patients
had stable disease (15%) and 16 had a progression (31%). No patient
progressing after paclitaxel responded to CGV, whereas 5 out of 15
patients with stable disease reached a partial response with CGV (33%).
On the contrary, 5 out of 29 patients with a partial response to
paclitaxel progressed after CGV (17%). Median survival has not been
reached after a median follow-up of 14 months. Median time to
progression was nine months. Fifty-six percent of patients remain alive
at one year. Two hundred eighty-nine courses of paclitaxel and 170 of
CGV were given, with a median of 5.5 and 3.4 per patient, respectively
(ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for
paclitaxel were: neutropenia in two patients (4/) and peripheral
neuropathy in five (10%). Two patients had allergic reactions requiring
paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml.
Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%),
peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting
in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%).
CONCLUSION: Our results suggest that sequential chemotherapy with weekly
paclitaxel followed by CGV is highly active in patients with advanced
NSCLC and has an acceptable toxicity. This schedule deserves further
evaluation in a phase III study.
20
UI - 11762807
AU - Jassem J; Ramlau R; Karnicka-Mlodkowska H; Krawczyk K; Krzakowski M;
TI -
Zatloukal P; Lemarie E; Hartmann W; Novakova L; O'Brien M; Depierr A
A multicenter randomized phase II study of oral vs. intravenous
vinorelbine in advanced non-small-cell lung cancer patients.
SO - Ann Oncol 2001 Oct;12(10):1375-81
AD - Department of Oncology and Radiotherapy, Medical University of Gdansk,
Poland. jjassem@amg.gda.pl
PURPOSE: A randomized phase II trial of oral vs. intravenous (i.v.)
vinorelbine was designed to determine the efficacy and safety of oral
vinorelbine with an intrapatient dose escalation in previously untreated
patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND
IIIB or IV NSCLC were randomized (2 to 1) to receive either oral
vinorelbine at a dose of 60 mg/m2/week for the first three
administrations and then increased to 80 mg/m2/week in the absence of
severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week. RESULTS: One
hundred and fourteen patients (76 in the oral arm and 38 in the i.v.
arm) were treated. Ninety-eight patients (86%) were eligible and
assessable. The two treatment arms were well-balanced for demographic
and prognostic features. After external panel review, the response rates
in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm.
The median progression-free survival with oral and i.v. vinorelbine was
3.2 months and 2.1 months, respectively, and the median survival 9.3 and
7.9 months, respectively. The most common hematological toxicity was
neutropenia, which was severe (grade 3-4) in 46% of patients and for 7%
of administrations in the oral arm, and in 62% of patients and for 25%
of administrations in the i.v. arm. Non-hematological toxicities
including nausea, vomiting, anorexia, weight loss, diarrhea .and
constipation were generally mild to moderate. CONCLUSION: The activity
of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable.
The safety profiles of both formulations look qualitatively similar.
Oral vinorelbine can therefore be considered a good alternative to i.v.
administration.
21
UI - 11762808
AU - Granberg D; Eriksson B; Wilander E; Grimfjard P; Fjallskog ML; Oberg K;
TI -
Skogseid B
Experience in treatment of metastatic pulmonary carcinoid tumors.
SO - Ann Oncol 2001 Oct;12(10):1383-91
AD - Department of Medicine, University Hospital, Uppsala, Sweden.
Dan.Granberg@medsci.uu.se
BACKGROUND: The only cure for patients with pulmonary carcinoids is
surgery. In the present paper, we report the results of medical
treatment of patients with metastatic tumors, their circulating hormone
markers, and immunohistochemical profile of the tumors. PATIENTS AND
METHODS/RESULTS: The response to systemic antitumoral treatment was
studied in 31 patients with metastatic pulmonary carcinoids. Median
survival from treatment start was 25 months. Alpha-interferon treatment
has resulted in stable disease in 4 of 27 patients (median duration 15
months), while 23 patients showed progressive disease. Somatostatin
analogues given as single drug treatment resulted in progressive
disease. Streptozotocin and 5-fluorouracil resulted in progressive
disease in seven of seven patients. Stable disease was obtained for 8
and 10 months respectively in two of two patients treated with
streptozotocin + doxorubicin. Two of eight patients treated with
cisplatinum + etoposide showed a significant decrease in tumor size
lasting six and eight months respectively, and one displayed stable
disease for seven months. Elevation of plasma chromogranin A was seen in
93%. CONCLUSIONS: The results of systemic antitumoral treatment of
pulmonary carcinoids with distant metastases are generally discouraging.
Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with
streptozotocin or paclitaxel may be of value. Alpha-interferon and
octreotide offer efficient symptomatic relief, but stabilizes tumor
growth in merely 15% of the cases. Plasma chromogranin A is the most
frequently elevated tumor marker.
22
UI - 11919225
AU - Neugut AI; Grann VR
TI -
Referral to medical oncologists: are there barriers at the gate?
SO - J Clin Oncol 2002 Apr 1;20(7):1716-8
23
UI - 11919235
AU - Earle CC; Neumann PJ; Gelber RD; Weinstein MC; Weeks JC
TI -
Impact of referral patterns on the use of chemotherapy for lung cancer.
SO - J Clin Oncol 2002 Apr 1;20(7):1786-92
AD - Center for Outcomes and Policy Research, Dana-Farber Cancer Center,
Boston, MA 02115, USA. craig_earle@dfci.harvard.edu
PURPOSE: To determine the extent to which unexplained variation in the
use of chemotherapy for advanced lung cancer is due to access to
oncologists' services as opposed to treatment decisions made after
seeing an oncologist. METHODS: We performed a retrospective cohort study
of 12,015 patients over age 65 diagnosed with metastatic lung cancer
between 1991 and 1996 while living in one of 11 regions monitored by a
Survival, Epidemiology, and End Results (SEER) tumor registry.
Assessment by an oncologist and subsequent treatment with chemotherapy
were determined by examining linked Medicare claims. RESULTS: Of
patients who did not receive chemotherapy, 36% were never assessed by a
physician who provides chemotherapy. Patients living in certain areas,
those diagnosed in more recent years, and those who received care in a
teaching hospital were all more likely to see a cancer specialist. These
factors were unrelated to subsequent treatment decisions, however.
Conversely, age and comorbidity did not have a significant effect on
whether a patient was seen by an oncologist, but they were associated
with the likelihood of subsequently receiving chemotherapy. Black race,
probably acting as a proxy for lower socioeconomic status, was
associated with both a diminished likelihood of seeing a cancer
specialist and subsequently receiving chemotherapy. CONCLUSION:
Nonmedical factors are important determinants of whether a lung cancer
patient is seen by a physician who provides chemotherapy. After seeing
such a physician, treatment decisions seem to be mostly explained by
appropriate medical factors. Racial and socioeconomic disparities still
exist at both steps, however. As therapeutic options expand, referring
physicians must ensure that biases and barriers to care do not deprive
patients of the opportunity to consider all of their treatment options.
24
UI - 11924242
AU - Morere JF
TI -
[Phase III clinical trials concerning non-small-cell lung carcinoma
(NSCLC) presented at the ASCO 2001]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S37-41
AD - Universite Paris XIII.
25
UI - 11924243
AU - Mavroudis D
TI -
[New therapeutic approaches in non-small-cell lung carcinoma (NSCLC),
stages IV]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S42-5
AD - Service d'oncologie, Hopital d'Heraklion, Crete.
26
UI - 11924244
AU - Douillard JY
TI -
[New prospects in the treatment of non-small-cell lung carcinoma
(NSCLC): new biological factors]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S46-9
AD - Service d'oncologie, Centre Rene Gauducheau, St-Herblain.
27
UI - 11780699
AU - Movsas B
TI -
Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung
cancer.
SO - Oncology (Huntingt) 2001 Dec;15(12):1549-58
AD - Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia,
Pennsylvania 19111, USA. B_Movsas@FCCC.edu
The role of adjuvant therapy following complete resection of
node-positive (stage II/IIIA) non-small-cell lung cancer remains
controversial. Five-year survival rates in pathologic stage II disease
range from 30% to 50% and in resected stage IIIA disease from 10% to
30%. The majority of recurrences following surgery are distant
metastases. This two-part review, which will conclude in the January
2002 issue, analyzes the role of adjuvant therapy in this setting, using
an evidence-based approach and focusing primarily on randomized trials
and meta-analyses. The key variables in evaluating these studies are
elucidated, ranging from the extent of mediastinal, systemic, and
"molecular" staging to the quality of the adjuvant treatments
administered. Some of the potential flaws inherent in meta-analyses are
reviewed. To date, there is no convincing evidence that any therapy
consistently improves survival in the adjuvant setting. Postoperative
radiotherapy has been associated with a significant improvement in local
control, particularly in patients with pathologic N2 disease.
Chemotherapy should be offered to patients in appropriate clinical
trials, and active phase III trials are reviewed. Future strategies
include novel chemotherapy, methods to reduce toxicity, the emerging
role of neoadjuvant therapy, and the promise of new biologic agents.
28
UI - 11780700
AU - Anonymous
TI -
Docetaxel combination produces 2-year survival advantage in NSCLC
patients.
SO - Oncology (Huntingt) 2001 Dec;15(12):1559, 1564
29
UI - 11804695
AU - Niho S; Ohe Y; Kakinuma R; Kubota K; Matsumoto T; Ohmatsu H; Goto K;
TI -
Nishiwaki Y
Phase II study of docetaxel and cisplatin administered as three
consecutive weekly infusions for advanced non-small cell lung cancer.
SO - Lung Cancer 2002 Feb;35(2):209-14
AD - Division of Thoracic Oncology, National Cancer Center Hospital East,
6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. siniho@east.ncc.go.jp
Weekly administration of low-dose taxane reduces myelosuppression and
increases dose intensity as compared with an every third week schedule.
We conducted a phase II trial of weekly docetaxel and cisplatin in
patients with advanced non-small cell lung cancer (NSCLC) to evaluate
safety and efficacy. Thirty-seven patients with chemonaive stage IIIB
(n=15), stage IV (n=16), or recurrence after operation (n=6) NSCLC
received intravenous infusions of docetaxel at 35 mg/m(2) and cisplatin
at 25 mg/m(2) for three consecutive weeks, followed by a week of rest.
There were ten partial responses for an objective response rate of 30%
(95% confidence interval (CI), 15-46%) in 33 evaluable patients and 27%
(95% CI, 13-41%) in the intent-to-treatment population. The median
survival was 12.8 months (range 2.5-17.1), and the 1-year survival was
54%. Hematologic toxicities, which were mild, included grade 4
neutropenia in 6%. There were none with febrile neutropenia or severe
(grade 3-4) infections, and no septic deaths. The common nonhematologic
toxicities included grade 2-3 nausea and vomiting (44%) and grade 2-3
diarrhea (14%). Consecutive weekly administrations of docetaxel and
cisplatin for 3 weeks produces minimal myelosuppression and shows
activity in the treatment of chemonaive patients with advanced NSCLC. A
randomized phase III trial is warranted to compare this 3 consecutive
weeks protocol with administration of docetaxel and cisplatin every
third week.
30
UI - 11888010
AU - Giaccone G
TI -
State of the art in systemic treatment of lung cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S99-114
AD - Vrije Universiteit Amsterdam, Department of Medical Oncology, The
Netherlands.
31
UI - 11948227
AU - Kusaba H; Tamura T; Shimoyama T; Hotta K; Inoue A; Nokihara H; Ueda Y;
TI -
Akiyama Y; Yamamoto N; Sekine I; Kunitoh H; Ohe Y; Kodama T; Saijo N
Phase I/II study of 3-week cycle cisplatin-gemcitabine in advanced
non-small cell lung cancer.
SO - Jpn J Clin Oncol 2002 Feb;32(2):43-7
AD - Division of Internal Medicine, National Cancer Center Hospital, Tokyo,
Japan.
BACKGROUND: The combination of cisplatin and gemcitabine is one of the
most active chemotherapy regimens against non-small cell lung cancer.
However, the optimum schedule for this combination has not been
determined. This study was performed to determine the maximum tolerated
dose of gemcitabine combined with cisplatin in a 3-week cycle regimen
and to observe safety and efficacy for Japanese patients with advanced
non-small cell lung cancer. METHODS: 80 mg/m(2) of cisplatin on day 1
and escalated doses of gemcitabine on days 1 and 8 were administered
every 3 weeks to patients with previously untreated, advanced non-small
cell lung cancer. The initial dose of gemcitabine was 1000 mg/m(2) and
was escalated in 250 mg/m(2) increments. RESULTS: Twenty-four patients
given. The main toxicities were neutropenia, thrombocytopenia and
hepatotoxicity. The maximum tolerated dose was determined to be 1500
mg/m(2) of gemcitabine combined with 80 mg/m(2 )of cisplatin. Nine of 24
patients (37.5%) achieved a partial response. CONCLUSION: This study
demonstrates that the combination of cisplatin and gemcitabine repeated
every three weeks is tolerable for Japanese patients with advanced
non-small cell lung cancer. We determined 1250 mg/m(2) of gemcitabine
combined with 80 mg/m(2 )of cisplatin to be the recommended dose.
32
UI - 11948228
AU - Ogawara M; Kawahara M; Hosoe S; Atagi S; Kawaguchi T; Okishio K; Naka N;
TI -
Sunami T; Mitsuoka S; Inoue K; Haryu H; Yoneda T; Origasa H
A feasibility study of paclitaxel 225 mg/m(2) and carboplatin AUC = 6 in
untreated advanced non-small cell lung cancer patients in Japan.
SO - Jpn J Clin Oncol 2002 Feb;32(2):48-53
AD - Department of Internal Medicine, National Kinki-Central Hospital for
Chest Diseases, Sakai, Osaka, Japan.
BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3 h infusion)
and carboplatin [area under the curve (AUC) 6 mg/ml x min] is used
widely for non-small cell lung cancer in the USA and is one of the
standard regimens in the Southwest Oncology Group. In Japan, however,
the upper limit of the approved dose for single-use paclitaxel is 210
mg/m(2) and the optimum dose of this agent in combination with
carboplatin has not yet been established. This study was designated to
determine whether the paclitaxel dose of 225 mg/m(2 ) plus carboplatin
(AUC = 6) is tolerable for Japanese patients with untreated advanced
non-small cell lung cancer. METHODS: Ten patients were enrolled between
toxicity. Chemotherapy consisted of carboplatin (AUC = 6 mg/ml x min)
and 225 mg/m(2 )of paclitaxel on day 1 every 3 weeks. RESULTS:
Neutropenia was the major toxicity and grade 4 neutropenia was observed
in seven of the 10 patients (70%), but febrile neutropenia was not
observed. Grade 4 anemia as a dose-limiting toxicity was observed in two
patients. This was due to gastric ulcer bleeding in both patients. Only
one patient experienced grade 3 peripheral neuropathy. No grade 3 or
more myalgia or arthralgia was reported. Overall, 44 courses of
chemotherapy were administered in 10 patients. Partial responses were
observed in six of the 10 patients (60%). Median survival time was 7.7
months. CONCLUSION: Paclitaxel at 225 mg/m(2) in a 3 h infusion and
carboplatin AUC = 6 appears to be tolerable in Japanese patients with
untreated advanced non-small cell lung cancer.
33
UI - 7506925
AU - Zangemeister-Wittke U; Collinson AR; Frosch B; Waibel R; Schenker T;
TI -
Stahel RA
Immunotoxins recognising a new epitope on the neural cell adhesion
molecule have potent cytotoxic effects against small cell lung cancer.
SO - Br J Cancer 1994 Jan;69(1):32-9
AD - Division of Oncology, University Hospital, Zurich, Switzerland.
The present study describes a comparison of two potent immunotoxins
which utilise an identical targeting component, a monoclonal antibody
(SEN7) specific for small cell lung cancer (SCLC), conjugated to two
different effector components, blocked ricin (bR) and Pseudomonas
exotoxin A (PE). SEN7 recognises a novel epitope on the neural cell
adhesion molecule (NCAM) which is highly associated with SCLC. The
immunotoxins SEN7-PE and SEN7-bR were selectively and potently active
against a number of SCLC cell lines, of both classic and variant
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