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Abramson Cancer Center
NCI CANCERLIT® Search: Chemotherapy for Non-small Cell Lung Cancer - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- OSI Pharmaceuticals, Genentech and Roche announce data from clinical studies of Tarceva.
- The early rad catches the tumor?
- Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell
- Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the
- The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma:
- Second-line chemotherapy for non-small cell lung cancer.
- Managing poor performance non-small-cell lung cancer patients.
- Do all patients with advanced non-small-cell lung cancer benefit from cisplatin-based combination therapy?
- The benefits of chemotherapy in patient subgroups with unresectable non-small-cell lung cancer.
- Oral vinorelbine: feasibility and safety profile.
- Second-line chemotherapy for non-small cell lung cancer.
- Genta initiates trials with Genasense.
- Irinotecan in the treatment of small cell lung cancer.
- Management of small cell lung cancer.
- Advances in systemic therapy of small cell cancer of the lung.
- New strategies in the treatment of resectable non-small cell lung cancer.
- Neoadjuvant chemotherapy in early-stage non-small cell lung cancer.
- Paclitaxel and carboplatin plus megestrol acetate in the treatment of advanced non-small cell lung cancer.
- Late activation of apoptotic pathways plays a negligible role in mediating the cytotoxic effects of discodermolide and epothilone B in
- Phase II clinical trial of XYOTAX in non-small cell lung cancer to continue.
- [Irinotekan in spread small cell lung cancer. More studies are required to change the practice]
- [Neo-adjuvant chemotherapy of non-small cell bronchial cancers (NSCLC)]
- Re: Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer.
- Paclitaxel, carboplatin, and vinorelbine in the treatment of advanced non-small cell lung cancer: a phase II trial of the Minnie Pearl Cancer
- Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative.
- Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.
- Sequential combination chemotherapy in patients with advanced nonsmall cell lung carcinoma. Carboplatin and gemcitabine followed by paclitaxel.
- Expanding horizons: an update on the use of docetaxel in non-small cell lung, ovarian, and breast cancers.
- Current and future therapeutic approaches in locally advanced (stage III) non-small cell lung cancer.
- Perspectives and opportunities: Docetaxel in the current and future treatment of non-small cell lung cancer.
- Docetaxel in combination with platinums (cisplatin or carboplatin) in advanced and metastatic non-small cell lung cancer.
Table of Contents
1
UI - 12113131
AU - Anonymous
TI -
OSI Pharmaceuticals, Genentech and Roche announce data from clinical
studies of Tarceva.
SO - Expert Rev Anticancer Ther 2001 Jun;1(1):4-5
2
UI - 12118015
AU - Machtay M
TI -
The early rad catches the tumor?
SO - J Clin Oncol 2002 Jul 15;20(14):3045-7
3
UI - 12118018
AU - Takada M; Fukuoka M; Kawahara M; Sugiura T; Yokoyama A; Yokota S;
TI -
Nishiwaki Y; Watanabe K; Noda K; Tamura T; Fukuda H; Saijo N
Phase III study of concurrent versus sequential thoracic radiotherapy in
combination with cisplatin and etoposide for limited-stage small-cell
lung cancer: results of the Japan Clinical Oncology Group Study 9104.
SO - J Clin Oncol 2002 Jul 15;20(14):3054-60
AD - Osaka Prefectural Habikino Hospital, Osaka City General Medical Center,
Kinki National Hospital for Chest Disease, Osaka, Japan.
PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT)
in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study
Group of the Japan Clinical Oncology Group conducted a phase III study
in which patients were randomized to sequential TRT or concurrent TRT.
PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT
consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients
were randomly assigned to receive either sequential or concurrent TRT.
All patients received four cycles of cisplatin plus etoposide every 3
weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day
2 of the first cycle of chemotherapy in the concurrent arm and after the
fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy
yielded better survival than sequential radiotherapy (P =.097 by
log-rank test). The median survival time was 19.7 months in the
sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and
5-year survival rates for patients who received sequential radiotherapy
were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8%
and 23.7%, respectively, for the patients who received concurrent
radiotherapy. Hematologic toxicity was more severe in the concurrent
arm. However, severe esophagitis was infrequent in both arms, occurring
in 9% of the patients in the concurrent arm and 4% in the sequential
arm. CONCLUSION: This study strongly suggests that cisplatin plus
etoposide and concurrent radiotherapy is more effective for the
treatment of LS-SCLC than cisplatin plus etoposide and sequential
radiotherapy.
4
UI - 12118020
AU - Papandreou CN; Daliani DD; Thall PF; Tu SM; Wang X; Reyes A; Troncoso P;
TI -
Logothetis CJ
Results of a phase II study with doxorubicin, etoposide, and cisplatin
in patients with fully characterized small-cell carcinoma of the
prostate.
SO - J Clin Oncol 2002 Jul 15;20(14):3072-80
AD - Department of Genitourinary Medical Oncology, The University of Texas
M.D. Anderson Cancer Center, Houston, TX 77030, USA.
cpapandr@notes.mdacc.tmc.edu
PURPOSE: To determine the activity and toxicity of doxorubicin in
combination with cisplatin and etoposide in patients with small-cell
prostate carcinoma (SCPCa) and to characterize the clinicopathologic
features of SCPCa. PATIENTS AND METHODS: Patients with SCPCa (pure or
mixed), measurable disease, good organ function, and no prior treatment
with doxorubicin, etoposide, or cisplatin were treated every 4 weeks
with doxorubicin 50 mg/m(2) as a 24-hour intravenous (IV) infusion
followed by etoposide 120 mg/m(2)/d and cisplatin 25 mg/m(2)/d IV on
days 2 to 4. RESULTS: Thirty-eight patients (36 assessable for response)
were treated for a median of four cycles. Twenty-nine (81%) of 36
patients had prior hormonal therapy. Study patients had visceral
metastases, lytic bone disease, and relatively low serum
prostate-specific antigen (PSA). We observed 22 partial responses
(response rate, 61% in an intent-to-treat analysis); toxicity was severe
(grade 3 or 4 neutropenia 100%, thrombocytopenia 66%, mucositis 21%, and
infection 68%). Three patients died of toxicity. Median time to
progression and overall survival time were 5.8 months and 10.5 months,
respectively. Performance status, serum albumin, and number of organs
involved (but not PSA, carcinoembryonic antigen, or neuroendocrine
markers) were predictors of survival. CONCLUSION: SCPCa presents unique
clinicopathologic features. Addition of doxorubicin to the
etoposide/cisplatin regimen caused higher toxicity in this patient
population and failed to improve outcome. Given these results, we do not
recommend further development of this regimen for patients with SCPCa.
Improvement in therapy will come from understanding the biology of SCPCa
progression and integrating new targeted therapies into the treatment of
SCPCa.
5
UI - 12124835
AU - Herbst RS; Khuri FR; Lu C; Liu DD; Fossella FV; Glisson BS; Pisters KM;
TI -
Shin DM; Papadimitrakopoulou VA; Kurie JM; Blumenschein G Jr; Kies MS;
Zinner R; Jung MS; Lu R; Lee JJ; Munden RF; Hong WK; Lee JS
The novel and effective nonplatinum, nontaxane combination of
gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma:
potential for decreased toxicity and combination with biological
therapy.
SO - Cancer 2002 Jul 15;95(2):340-53
AD - Department of Thoracic/Head & Neck Medical Oncology, The University of
Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
rherbst@mdanderson.org
BACKGROUND: Gemcitabine and vinorelbine are two of the most active
third-generation agents for the treatment of advanced nonsmall cell lung
carcinoma (NSCLC). The authors conducted a formal Phase II trial to
evaluate the efficacy of this combination in both untreated and
previously treated patients with Stage IIIB (with pleural effusion) or
Stage IV NSCLC. METHODS: A total of 78 patients were treated on the
current Phase II trial of front-line or second/third-line therapy with
gemcitabine and vinorelbine in NSCLC. Eligible patients manifested
either untreated disease (n = 42) or had received at least one but not
more than two prior chemotherapy regimens (n = 36). The median age was
59 years (range, 33-79) with 57 men (73%) and 21 women (27%). The median
performance status was one (range, one to two). The initial eight
patients (four untreated and four previously treated) were treated at a
previously established maximum tolerated dose of vinorelbine (30
mg/m(2)) and gemcitabine (1000 mg/m(2)) on Days 1, 8, and 15, with
significant myelosuppression seen in five out of eight patients
requiring dose omission in the first cycle. The next 70 patients
received a reduced dose of vinorelbine (25 mg/m(2)) followed by
gemcitabine (900 mg/m(2)) on Days 1, 8, and 15. RESULTS: Seventy eight
patients were treated. Fifteen (36%) of the 42 evaluable patients who
received front-line therapy had objective responses and 14 (33%) had
stable disease. In the patients with prior treatment, 6 (17%) of 36
patients had partial response and 18 patients (50%) had stable disease.
Median survival time for the previously untreated patient group was 10.1
months, with a one year survival of 43% and a two year survival rate of
32%. For the previously treated patients, the median survival time was
8.5 months, with a one year survival rate of 30%. Toxic effects were
notable for significant myelosuppression, with > or =Grade 3
granulocytopenia seen in 55% of the patients on the untreated arm and
67% of the patients on the previously untreated arm. Additionally, 9.5%
and 13.9% (untreated and previously treated), respectively, of these
patients experienced Grades 3 and 4 thrombocytopenia at some point in
their treatment. A full dose delivery analysis showed that this
myelosuppression resulted in Course 1, Day 15 skipped doses (even at the
reduced dose level) in 42% of previously untreated patients and 47% of
pretreated patients. Other side effects seen at Grades 3 and 4 in
previously untreated and treated patients included anemia (9.5% and
2.8%), asthenia (4.8% and 5.5%), infection (14.3% and 5.6%), pain (9.5%
and 19.4%), and pulmonary complications (4.8% and 13.8%). CONCLUSIONS:
Gemcitabine/vinorelbine is an active, well-tolerated combination in both
front-line and second/third-line therapy for Stage IIIB/IV NSCLC. The
response rate, median survival rate, and one year survival rate compare
favorably with platinum-based regimens. The toxicity profile of the
gemcitabine/vinorelbine combination was quite favorable, with minimal
Grade 3 and 4 toxic effects aside from granulocytopenia, which resulted
in numerous Day 15 skipped doses but no significant febrile neutropenia
or infection. The combination of gemcitabine and vinorelbine could be a
useful regimen in standard clinical practice and has the potential for
efficient combination with biologic/targeted therapy. Multiple
randomized trials of this combination versus platinum combinations are
now ongoing.
6
UI - 11687161
AU - Bonfill X; Serra C; Sacristan M; Nogue M; Losa F; Montesinos J
TI -
Second-line chemotherapy for non-small cell lung cancer.
SO - Cochrane Database Syst Rev 2001;(4):CD002804
AD - Centro Cochrane Iberoamericano., Hospital de la Santa Creu i Sant Pau,
Sant Antoni M. Claret 171, Barcelona, Catalonia, Spain, 08041.
XBonfill@hsp.santpau.es
BACKGROUND: The role of second-line chemotherapy for the treatment of
patients with non-small cell lung cancer (NSCLC) who have relapsed or
failed to respond to first-line treatment was unclear. OBJECTIVES: To
determine the effectiveness of any second-line chemotherapy in patients
with NSCLC. SEARCH STRATEGY: Bibliographic databases were searched.
Handsearching and contact with experts was also performed. SELECTION
CRITERIA: Randomised controlled clinical trials in which any second-line
chemotherapy was compared with BSC in patients with NSCLC who had
previously failed to any previous chemotherapy regimen. DATA COLLECTION
AND ANALYSIS: Data was extracted by 2 independent reviewers and revised
by all authors. MAIN RESULTS: Only one study was included. It randomised
204 patients to receive either doxetaxel or BSC. Following an
unacceptably high toxic death rate the dose of doxetaxel was reduced
from 100 mg/m(2) to 75 mg/m(2). Doxetaxel gave an extra 2.4 months of
survival - an average of 7.0 months vs 4.6 months on BSC. At 1 year
after diagnosis 29% of doxetaxel treated patients were alive compared
with 19% of the BSC group. REVIEWER'S CONCLUSIONS: Definitive
recommendations cannot be made since evidence is only available from one
randomised controlled trial which, though of reasonable quality, had a
number of limitations. There is currently no evidence to support
second-line treatment of patients with poor performance status. Larger,
well-designed controlled trials are needed to further evaluate whether
the benefits of second-line chemotherapy to patients with NSCLC outweigh
its risks and costs.
7
UI - 11843240
AU - Rosell R
TI -
Managing poor performance non-small-cell lung cancer patients.
SO - Ann Oncol 2001 Dec;12(12):1659-61
8
UI - 11843242
AU - Soria JC; Brisgand D; Le Chevalier T
TI -
Do all patients with advanced non-small-cell lung cancer benefit from
cisplatin-based combination therapy?
SO - Ann Oncol 2001 Dec;12(12):1667-70
AD - Department of Medicine, Institut Gustave Roussy, Villejuif, France.
BACKGROUND: Platinum-based chemotherapy has been shown to be effective
in improving survival and quality of life in advanced non-small-cell
lung cancer (NSCLC) patients. The objective of this study was to
identify patients more likely to benefit from chemotherapy in order to
avoid the indiscriminate treatment of all patients. PATIENTS AND
METHODS: A multivariate analysis of survival was performed using the
database of the European randomized phase III trial that compared
vinorelbine (navelbine) (NVB), vinorelbine-cisplatin (NVB-P) and
vindesine-cisplatin (VDS-P) in 612 patients with inoperable NSCLC (stage
III or IV). Interactions between treatment and the prognostic factors
singled out by the Cox procedure were specifically tested. RESULTS: The
performance status (PS) was the only significant interaction among the
selected prognostic factors and treatment. Subgroup analysis showed that
the advantage obtained with NVB-P predominantly concerned PS 0-1
patients, whose median survival lasted 43 weeks (95% confidence interval
(95% CI): 39-50 weeks) with a one-year survival rate of 38% (95% CI:
31%-46%) versus 36 weeks (95%, CI: 30-40 weeks) and 34% (95% CI:
27%-42%) for NVB alone, and 33 weeks (95% CI: 30-39 weeks) and 29% (95%
CI: 22%-36%) for VDS-P. In sharp contrast, survival in PS 2 patients was
similar (median 18 weeks) (NVB-P 95% CI: 11-34 weeks; NVB 95% CI: 11-35
weeks; VDS-P 95% CI: 14-32 weeks) whatever the treatment. CONCLUSION: PS
2 patients with advanced NSCLC might not benefit from cisplatin
combination therapy.
9
UI - 11843243
AU - Billingham LJ; Cullen MH
TI -
The benefits of chemotherapy in patient subgroups with unresectable
non-small-cell lung cancer.
SO - Ann Oncol 2001 Dec;12(12):1671-5
AD - Cancer Research Campaign Trials Unit, Institute for Cancer Studies, The
Medical School, University of Birmingham, Edgbaston, UK.
L.J.Billingham@bham.ac.uk
BACKGROUND: Cisplatin-based chemotherapy improves survival in advanced
non-small-cell lung cancer. Using data from phase III trials of
mitomycin, ifosfamide and cisplatin, this paper investigates whether the
beneficial effect of chemotherapy on survival and quality of life seen
overall is limited to certain patient subgroups. PATIENTS AND METHODS:
The survival benefit of chemotherapy was compared with standard
treatment using hazard ratios for subgroups specified by stage, sex,
age, histology and performance status (PS). The effect on quality of
life was investigated for three subgroups defined by performance status.
RESULTS: The overall unstratified hazard ratio for all 797 eligible
patients shows a 16% reduction in the risk of death with chemotherapy (P
= 0.02). This benefit was seen for both locally advanced and extensive
stage disease (significantly in extensive disease). Subgroups defined by
sex, age and histology consistently benefitted from chemotherapy. The
hazard ratios for the three levels of performance status suggest that
PS2 patients gain no survival benefit from chemotherapy. In contrast,
these patients experienced the greatest improvement in quality of life
during the first six weeks of chemotherapy. CONCLUSIONS: Subgroup
analysis suggests that the prolongation of life from cisplatin-based
chemotherapy is confined to PS0/1 patients. Palliation is greater in PS2
patients.
10
UI - 11843244
AU - Depierre A; Freyer G; Jassem J; Orfeuvre H; Ramlau R; Lemarie E;
TI -
Koralewski P; Mauriac L; Breton JL; Delozier T; Trillet-Lenoir V
Oral vinorelbine: feasibility and safety profile.
SO - Ann Oncol 2001 Dec;12(12):1677-81
AD - Department of Pneumology, Centre Hospitalier Universitaire Minjoz,
Besancon, France.
BACKGROUND: Patient preference as well as concerns and difficulties with
intravenous access and pharmaco-economic issues have driven the
development of oral vinorelbine. PATIENTS AND METHODS: Four phase II
studies were conducted in chemotherapy-naive non-small-cell lung cancer
(NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC).
As recommended in the phase I dose-finding study, the first step used a
weekly dose of 80 mg/m2. This regimen was associated with an excessive
rate of early deaths (10%) due to complicated neutropenia and led to
discontinuation of the first two studies. In a second step, the dose of
60 mg/m2/week was given for the first three courses and subsequently
increased to 80 mg/m2/week, in the absence of severe neutropenia.
RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62
with ABC) received this regimen, of whom only five were unable to
undergo dose escalation. The incidence of febrile neutropenia and
neutropenic sepsis were low (2.9 and 3.6%, respectively). Although
severe events were uncommon, nausea/vomiting and diarrhoea were frequent
and primary prophylaxis with antiemetics should be recommended.
CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60
mg/m2/week for the first three courses with escalation to 80 mg/m2 is
qualitatively comparable to that of i.v. vinorelbine at standard doses.
Similarly to i.v. chemotherapy, close haematological monitoring is
necessary.
11
UI - 12076452
AU - Bonfill X; Serra C; Sacristan M; Nogue M; Losa F; Montesinos J
TI -
Second-line chemotherapy for non-small cell lung cancer.
SO - Cochrane Database Syst Rev 2002;(2):CD002804
AD - Centro Cochrane Iberoamericano, Hospital de la Santa Creu i Sant Pau,
Casa de Convalescencia, C/ Sant Antoni M. Claret 171, Barcelona,
Catalunya, Spain, 08041. xbonfill@hsp.santpau.es
BACKGROUND: The role of second-line chemotherapy for the treatment of
patients with non-small cell lung cancer (NSCLC) who have relapsed or
failed to respond to first-line treatment was unclear. OBJECTIVES: To
determine the effectiveness of any second-line chemotherapy in patients
2001), Cancerlit (1993-July) and the Cochrane Controlled Trials Register
(CENTRAL, issue 2 2001) were searched. In addition a handsearch was
performed and experts in the field contacted to identify any further
studies that had not been found by the electronic searches. SELECTION
CRITERIA: Randomised controlled clinical trials in which any second-line
chemotherapy was compared with placebo or best supportive care in
patients with NSCLC who had previously failed to any previous
chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Data were extracted
by 2 independent reviewers and revised by a third author. MAIN RESULTS:
Only one study was included. This study included a total of 204 patients
who were randomised to receive either doxetaxel or best supportive care.
Following an unacceptably high toxic death rate the dose of doxetaxel
was reduced from 100 mg/m(2) to 75 mg/m(2). Docetaxel gave an extra 2.4
months survival - an average of 7.0 months vs 4.6 months on best
supportive care. At 1 year after diagnosis 29% of doxetaxel treated
patients were alive compared with 19% of the best supportive care group.
REVIEWER'S CONCLUSIONS: Definitive recommendations cannot be made since
evidence is only available from one randomised controlled trial which,
though of reasonable quality had a number of limitations. There is
currently no evidence to support second-line treatment of patients with
poor performance status. Larger, well-designed controlled trials are
needed to further evaluate whether the benefits of second-line
chemotherapy to patients with non-small cell lung cancer outweigh its
risks and costs.
12
UI - 12113068
AU - Anonymous
TI -
Genta initiates trials with Genasense.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):6
13
UI - 12113024
AU - Masuda N; Fukuoka M
TI -
Irinotecan in the treatment of small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):187-95
AD - Department of Respiratory Disease, Otemae Hospital, 1-5-34 Otemae,
Chuo-ku, Osaka, Osaka, 540-0008, Japan.
Combination chemotherapy is the cornerstone of treatment of small cell
lung cancer, leading to a meaningful survival benefit for these
patients. However, there have been no major advances in therapy in the
last decade. Therefore, more effective new treatments are necessary to
improve the outcome of therapy. Irinotecan is one of the new active
agents that provide hope for more effective therapies in the 21st
century. A Phase III trial carried out in Japan clearly demonstrated a
survival advantage of a combination of cisplatin and irinotecan over the
standard regimen of cisplatin and etoposide. This review outlines the
treatment results of irinotecan as a single agent as well as in
combination with other cytotoxic agents.
14
UI - 12113025
AU - Yip D; Karapetis C; Steer C
TI -
Management of small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):197-210
AD - Medical Oncology Unit, Canberra Hospital, Garran ACT 2605, Australia.
dyip@med.usyd.edu.au
Small cell lung cancer is a tumor that has a very poor prognosis without
treatment. It is however, highly responsive to chemotherapy and
radiotherapy. Pretreatment clinical and laboratory parameters--in
addition to staging--can prognosticate outcome and help define the aim
of treatment. Different schedules of chemotherapy have been developed
and varied strategies, such as chemotherapy dose intensification have
been tried to improve outcomes. New agents, such as irinotecan,
gemcitabine and topotecan have also been tested. Clinical trials have
helped to define strategies of integrating thoracic radiotherapy and
prophylactic cranial radiotherapy into management of those patients with
limited disease to improve survival further. Despite good initial
responses to treatment, most patients eventually relapse. Maintenance
strategies with ongoing chemotherapy or novel agents, such as
interferon, matrix metalloproteinase inhibitors, thalidomide and
vaccines are discussed.
15
UI - 12113026
AU - Daniels GA; Adjei AA
TI -
Advances in systemic therapy of small cell cancer of the lung.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):211-21
AD - Division of Medical Oncology, Mayo Clinic, 200 First St. SW, Rochester,
MN 55905, USA.
Over the last 20 years, progress in the therapy of small cell lung
cancer has been painfully slow. Despite dramatic initial responses to
chemotherapy, most patients relapse quickly with an overall 5-year
survival of about 5%. Recent trials however offer some hope at changing
this picture. Combining standard regimens with newer agents has doubled
median survival in some cases. The use of novel targeted agents holds
the promise of significantly increasing the survival in this disease,
with manageable toxicity. This review outlines current treatment
strategies, summarizes recent clinical trials and offers a view of what
the next 5 years may hold for the treatment of small cell lung cancer.
16
UI - 12113027
AU - Felip E; Rosell R
TI -
New strategies in the treatment of resectable non-small cell lung
cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):224-8
AD - Medical Oncology Service, Hospital Germans Trias i Pujol, Ctra Canyet
s/n, 08916 Badalona, Barcelona, Spain.
Non-small cell lung cancer is a systemic illness. Given the systemic
nature of lung cancer, it seems that chemotherapy should play an
essential role. In stage IIIA disease neoadjuvant chemotherapy plus
surgical resection improves survival when compared with surgical
resection alone. However, randomized trials using postoperative adjuvant
chemotherapy with 'older' drugs has shown no substantial improvement in
survival. Since new chemotherapeutic agents may provide additional
benefits, there are various studies incorporating new agents in the
resectable disease treatment setting. One focus for ongoing research is
to find better treatment approaches in earlier stages of disease. Some
data suggest that induction chemotherapy in stage I-II is feasible and
appears not to compromise surgery. Another promising more individual
approach is to tailor chemotherapy according to the pattern of genetic
variants or abnormalities found in DNA and/or RNA extracted from the
bloodstream. Furthermore, at present many types of new agents are
available for testing as 'consolidation treatment' following induction
treatment, including, angiogenesis inhibitors, antibodies to growth
factor receptors, gene therapy and vaccines.
17
UI - 12113028
AU - Edelman MJ
TI -
Neoadjuvant chemotherapy in early-stage non-small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):229-35
AD - University of Maryland, Greenebaum Cancer Center, Baltimore, Maryland,
USA. medelman@umm.edu
Of the patients that undergo complete resection of early-stage non-small
cell lung cancer (NSCLC), 30-60% will die. Postoperative adjuvant
chemotherapy has yet to demonstrate an unequivocal benefit and there are
significant difficulties in administering postoperative chemotherapy to
patients with the significant comorbidities found in NSCLC. Currently,
several trials are evaluating the role of preoperative chemotherapy in
stage I and II NSCLC. This paper reviews the rationale for this approach
and potential future developments.
18
UI - 12118488
AU - Thongprasert S; Cheewakriangkrai R; Euathrongchit J; Thaikla K
TI -
Paclitaxel and carboplatin plus megestrol acetate in the treatment of
advanced non-small cell lung cancer.
SO - J Med Assoc Thai 2002 Apr;85(4):424-32
AD - Department of Medicine, Faculty of Medicine, Chiang Mai University,
Thailand.
The present study evaluated the efficacy and toxicity of paclitaxel and
carboplatin with megestrol acetate for patients with stage IIIb and IV
non-small cell lung cancer (NSCLC). Forty patients with no prior
chemotherapy and Karnofsky performance status of > or = 60 were enrolled
in the study. There were 18 males and 22 females with a median age of
57.5 years, and the median performance status was 70 per cent. Eleven
cases were stage IIIb and 29 cases were stage IV. Twenty-five cases were
adenoCA, 12 were squamous cell, 2 were large cell and one was
undifferentiated NSCLC. These patients received paclitaxel 135 mg/m2 by
intravenous infusion over 24 hours before carboplatin was given at AUC=6
by 2 hours infusion. Megestrol acetate 160 mg/day was given to all
patients from day 2 to 14. This treatment produced partial remission in
12 of 39 evaluable patients (30.76%). Toxicity caused mild nausea,
vomiting, myalgia, neuropathy, 20.95 per cent grade 3 neutropenia and
4.15 per cent grade 4 neutropenia. Grade 3 thrombocytopenia was 5.4 per
cent, without grade 4. There were no statistically significant changes
in weight, serum albumin, and quality of life throughout the cycle 1-6.
Conclusion: The addition of megestrol acetate to chemotherapy benefitted
these patients by minimizing constitute symptoms throughout the
treatment period especially in the quality of life, weight loss and
stabilized serum albumin.
19
UI - 12124345
AU - Broker LE; Huisman C; Ferreira CG; Rodriguez JA; Kruyt FA; Giaccone G
TI -
Late activation of apoptotic pathways plays a negligible role in
mediating the cytotoxic effects of discodermolide and epothilone B in
non-small cell lung cancer cells.
SO - Cancer Res 2002 Jul 15;62(14):4081-8
AD - Department of Medical Oncology, Vrije University Medical Center, 1081 HV
Amsterdam, the Netherlands.
Discodermolide and epothilone B are promising novel chemotherapeutic
agentsthat induce cell death through potent stabilization of
microtubules. In this study, we investigated the cellular and molecular
events underlying the cytotoxicity of these drugs in non-small cell lung
carcinoma (NSCLC) cell lines, focusing on apoptotic characteristics.
IC80 concentrations of either drug effectively disrupted the microtubule
cytoskeleton of H460 cells and induced cell cycle disturbances with
early accumulation in the G2-M phase and development of a hypodiploid
cell population in both H460 and SW1573 cells. These events were
followed by abnormal chromosome segregation during mitosis and
subsequent appearance of multinucleated cells. At later time points, the
cells displayed several apoptotic features, such as nuclear condensation
and fragmentation as well as Annexin V staining, cleavage of
poly(ADP-ribose) polymerase and the activation of caspases. To examine
the contribution of apoptotic pathways to the cytotoxic effects of these
agents, the involvement of the mitochondria and death receptor routes
was studied. At 48 h after treatment, both agents disrupted mitochondria
of H460 cells, as indicated by cytochrome c release. Nonetheless, H460
cells stably overexpressing antiapoptotic Bcl-2 or Bcl-xL did not show
any protective effect from cell death induced by either drug. Possible
death receptor dependency was investigated in H460 cells stably
overexpressing dominant-negative FADD, which failed to reduce the
cytotoxic effects of discodermolide and epothilone B. To study the role
of caspases more directly, the effect of stable overexpression of the
caspase-8 inhibitor cytokine response modifier A was studied in H460
cells. Furthermore, the effect of the pancaspase inhibitor
z-Val-Ala-Asp-fluoromethyl ketone was investigated in a panel of lung
carcinoma cell lines. Interestingly, caspase inhibition did not rescue
cells from discodermolide or epothilone B-induced cell death. In
conclusion, these results demonstrate that despite several apoptotic
features detected at relatively late time points after drug exposure,
apoptosis is not the dominant mode of cell death and induced low but
efficacious concentrations of discodermolide and epothilone B.
20
UI - 12113042
AU - Anonymous
TI -
Phase II clinical trial of XYOTAX in non-small cell lung cancer to
continue.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):244-5
21
UI - 12090170
AU - Sorenson S
TI -
[Irinotekan in spread small cell lung cancer. More studies are required
to change the practice]
SO - Lakartidningen 2002 May 23;99(21):2409
AD - Lungeavdelingen, Haukeland sykehus, Bergen, Norge.
22
UI - 12148364
AU - Milleron B; Westeel V; Depierre A
TI -
[Neo-adjuvant chemotherapy of non-small cell bronchial cancers (NSCLC)]
SO - Presse Med 2002 May 11;31(17):797-801
AD - Service de pneumologie, Hopital Tenon, 4, rue de la Chine, 75020 Paris.
TO PROLONG SURVIVAL: Systemic neo-adjuvant chemotherapy attempts to
reduce the development of metastases. Data available on neoadjuvant
chemotherapy of NSCLC come from three types of clinical trials.
NEO-ADJUVANT CHEMOTHERAPY PHASE II TRIALS: Many trials have demonstrated
that the neo-adjuvant approach is feasible, that it leads to a high rate
of response, to the order of 50 to 70%, that it does not compromise
surgery, and exhibits acceptable toxicity. High survival rates have been
obtained, notably in total responders. NEO-ADJUVANT CHEMO-RADIOTHERAPY
PHASE II TRIALS: Have essentially demonstrated that this approach is
feasible, exhibits acceptable toxicity, worse in pneumonectomy. High
response rates have been obtained and relative improved survival, since
most of the cases concerned extensive forms that could not be treated
surgically. RANDOMIZED PHASE III TRIALS: Gave varying results: two of
them only concerned small series of patients (60 in all) with stage IIIA
NSCB, with positive results. The third study concerned 373 patients with
stage I, II and IIIA cancers: survival at 3 years was increased by 11%,
but this difference is not yet significant. Benefits were essentially
apparent for stage I and II patients. IN THE FUTURE: Continued active
clinical research, oriented differently, on stage I and II, and stage
IIIA is necessary.
23
UI - 12165643
AU - Malayeri R
TI -
Re: Economic analysis of vinorelbine plus cisplatin versus paclitaxel
plus carboplatin for advanced non-small-cell lung cancer.
SO - J Natl Cancer Inst 2002 Aug 7;94(15):1172; discussion 1172
24
UI - 10882330
AU - Hainsworth JD; Burris HA 3rd; Morrissey LH; Thomas M; Erland JB; Butts
TI -
JA; Joseph G; Kalman L; Greco FA
Paclitaxel, carboplatin, and vinorelbine in the treatment of advanced
non-small cell lung cancer: a phase II trial of the Minnie Pearl Cancer
Research Network.
SO - Cancer J 2000 May-Jun;6(3):151-6
AD - Sarah Cannon-Minnie Pearl Cancer Center, Nashville, Tennessee 37202,
USA.
PURPOSE: To evaluate the feasibility, toxicity, and efficacy of adding
vinorelbine to the paclitaxel/carboplatin combination in the treatment
of advanced non-small cell lung cancer. PATIENTS AND METHODS: Patients
with advanced (stage IIIB/IV) non-small cell lung cancer who had
received no previous chemotherapy were treated with the following
three-drug regimen: paclitaxel, 200 mg/m2, 1-hour i.v. infusion, day 1;
carboplatin, AUC 6.0 i.v., day 1; and vinorelbine, 22.5 mg/m2 i.v. days
1 and either 8 or 15. Treatment was repeated every 21 days. This phase
II trial was conducted in a multicenter, community-based setting.
RESULTS: Eighty-nine patients were treated with a median of four courses
of therapy (range, one to eight). Thirty-one patients (35%) had major
responses (two complete, 29 partial), and 36 patients (40%) had a minor
response or stable disease. Actuarial median survival was 8.6 months; 1
year survival was 43%. Leukopenia was the major toxicity: 73% of
patients had grade 3/4 toxicity, and 32 patients (36%) were hospitalized
for neutropenia/fever (11% of total courses administered).
Treatment-related death due to infection occurred in four patients (4%).
CONCLUSIONS: This three-drug regimen is feasible and efficacious in the
treatment of advanced non-small cell lung cancer. The addition of
vinorelbine increases the incidence of severe leukopenia substantially
when compared with the paclitaxel/carboplatin regimen. However, other
toxicities are not markedly increased. Ongoing randomized trials will
define the role of this regimen in the treatment of non-small cell lung
cancer.
25
UI - 10960939
AU - Cappuzzo F; Rocha Lima CM; Sherman CA; Green MR
TI -
Advances in treatment of inoperable NSCLC: gemcitabine doublets--a
promising alternative.
SO - Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):7-14
AD - Division of Hematology/Oncology, Hollings Cancer Center, Medical
University of South Carolina, Charleston, USA.
Gemcitabine (Gemzar) was originally approved for use in combination with
cisplatin (Platinol) for the treatment of advanced non-small-cell lung
cancer (NSCLC). Research began to focus on combining gemcitabine with
newer drugs, such as carboplatin (Paraplatin), vinorelbine (Navelbine),
the taxanes, and the camptothecins, when it became clear that these
agents had potentially increased efficacy and fewer side effects than
the standard treatment. This article will briefly review the original
experience with the gemcitabine/cisplatin doublet and then examine the
experience to date with non-cisplatin-based gemcitabine doublet
combinations in the treatment of advanced NSCLC.
26
UI - 12151970
AU - Perez JE; Machiavelli MR; Romero AO; Romero Acuna LA; Dominguez ME;
TI -
Fasce H; Flores Acosta L; Marrone N; Romero Acuna JM; Langhi MJ; Amato
S; Bologna F; Ortiz EH; Leone BA; Lacava JA; Vallejo CT
Vinorelbine and paclitaxel for locoregional advanced or metastatic
non-small-cell lung cancer.
SO - Am J Clin Oncol 2002 Aug;25(4):383-7
AD - Grupo Oncologico Cooperativo del Sur (G.O.C.S.), Republica Argentina.
A phase II trial was performed to evaluate the efficacy and toxicity of
the novel combination of vinorelbine and paclitaxel as first-line
chemotherapy in patients with stages IIIB and IV non-small-cell lung
and 25 stage IV) received a regimen consisting of the following:
vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and
8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after
vinorelbine) on day 1. Cycles were repeated every 28 days until
progression of disease or unacceptable toxicity development. The median
age was 57 years (range 41-70 years); median performance status was 1.
Histology was as follows: squamous cell in 24 (71%), large cell in 1
(3%), and adenocarcinoma in 9 (26%). All patients are evaluable for
toxicity, whereas 30 are evaluable for response (4 patients refused
treatment). Objective response was recorded in 4 of 30 patients (13%,
95% CI 1-25%). No complete response was observed. Partial response was
recorded in 4 patients (13%), no change in 10 patients (34%), and
progressive disease in 16 patients (53%). The median time to treatment
failure was 4 months and median survival was 9 months. The limiting
toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas
neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity
developed in 14 patients (41%) (without G3 or G4 episodes), and
constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients),
diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7
patients. Vinorelbine-paclitaxel combination showed only modest activity
against locoregionally advanced or metastatic NSCLC.
27
UI - 12173351
AU - De Castro J; Feliu J; Casado E; Ordonez A; Gonzalez Baron M
TI -
Sequential combination chemotherapy in patients with advanced nonsmall
cell lung carcinoma. Carboplatin and gemcitabine followed by paclitaxel.
SO - Cancer 2002 May 15;94(10):2797-8; discussion 2798-9
28
UI - 12170444
AU - Hortobagyi GN; Kris MG
TI -
Expanding horizons: an update on the use of docetaxel in non-small cell
lung, ovarian, and breast cancers.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):1-3
AD - University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
29
UI - 12170446
AU - Davies A; Gandara DR; Lara P; Goldberg Z; Roberts P; Lau D
TI -
Current and future therapeutic approaches in locally advanced (stage
III) non-small cell lung cancer.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):10-6
AD - Division of Hematology/Oncology, University of California Davis Cancer
Center, Sacramento, CA 95817-2229, USA.
In the treatment of locally advanced (stage III) non-small cell lung
cancer, randomized clinical trials have shown that sequential
administration of platinum-based chemotherapy followed by radiotherapy
improves outcome compared with radiotherapy alone. More recently,
concurrent chemoradiotherapy has been shown to be superior to sequential
therapy. Incorporating full-dose chemotherapy into induction or
consolidation phases is aimed at the eradication of distant
micrometastases. These approaches are currently being examined in
clinical trials. The role of neoadjuvant and adjuvant therapy in
resectable stage IIIA patients remains controversial. Integration of
newer cytotoxic agents (paclitaxel, docetaxel, gemcitabine, vinorelbine,
and irinotecan) and molecularly targeted agents into the treatment of
stage-III patients may result in improved long-term outcomes and is
currently under study. Copyright 2002, Elsevier Science (USA). All
rights reserved.
30
UI - 12170447
AU - Green MR
TI -
Perspectives and opportunities: Docetaxel in the current and future
treatment of non-small cell lung cancer.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):17-21
AD - Department of Medicine, Medical University of South Carolina, Charleston
29425, USA.
Docetaxel is active as monotherapy in patients with advanced or
metastatic non-small cell lung cancer. In addition to the conventional
3-weekly regimen, docetaxel delivered in smaller, weekly doses to
patients who are elderly or have comorbidities maintains activity while
minimizing myelosuppression. Randomized phase III trials show that
docetaxel monotherapy improves survival when compared with best
supportive care in both first- and second-line settings. More recently,
the combination of docetaxel with cisplatin in chemotherapy-naive
patients has been shown to be significantly superior to the
vinorelbine/cisplatin combination in terms of both increased survival
and reduced toxicity. Docetaxel can be combined with nonplatinum agents
such as gemcitabine to produce regimens that have substantial activity
and a favorable therapeutic index. In multimodality therapy, following
platinum/etoposide chemoradiation with docetaxel may have played an
important role in the encouraging outcome of the recent Southwest
Oncology Group 9504 study. If this can be confirmed, docetaxel appears
suitable for inclusion in a range of sequential chemoradiotherapy
approaches. Docetaxel can safely be combined with a platinum in patients
receiving thoracic radiotherapy; and the combination is a candidate for
induction therapy in patients with stage IB-IIIA disease. There is also
considerable promise in combining docetaxel with any of the large number
of molecularly targeted therapies now becoming available. Copyright
2002, Elsevier Science (USA). All rights reserved.
31
UI - 12170445
AU - Belani CP; TAX 326 Study Group
TI -
Docetaxel in combination with platinums (cisplatin or carboplatin) in
advanced and metastatic non-small cell lung cancer.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):4-9
AD - Lung and Thoracic Cancer Program, University of Pittsburgh Cancer
Institute, PA.
In a large, multinational, randomized phase III trial, 1,220 patients
with advanced and/or metastatic non-small cell lung cancer were
randomized to receive one of three treatments: docetaxel 75 mg/m(2) plus
cisplatin 75 mg/m(2) every 3 weeks; docetaxel 75 mg/m(2) plus
carboplatin to an AUC of 6 every 3 weeks; or a standard reference arm of
vinorelbine given at 25 mg/m(2) on days 1, 8, 15, and 22 plus cisplatin
100 mg/m(2) on day 1 every 4 weeks. The choice of treatment and dose was
based on a series of four phase II studies that indicated the
combination of docetaxel (75 to 100 mg/m(2)) and cisplatin (75 to 100
mg/m(2)) was active and feasible; carboplatin may have a more favorable
therapeutic index than cisplatin, particularly with regard to
nonhematologic toxicities, and had proven activity in combination with
docetaxel in phase II study; and randomized studies had shown the
combination of vinorelbine plus cisplatin was superior to either
vinorelbine alone or cisplatin alone and was considered as a reference
study regimen in the clinical setting upon initiation of this phase III
study. Preliminary results of the phase III trial showed that the
overall survival among patients randomized to receive docetaxel plus
cisplatin was significantly better than that among patients treated with
vinorelbine/cisplatin and similar between the docetaxel plus carboplatin
versus control arm. The three arms were similar for toxicity data,
except the use of vinorelbine plus cisplatin was associated with a
significantly greater incidence of grade (3/4) anemia and nausea and
vomiting than use of docetaxel plus either cisplatin or carboplatin.
Copyright 2002, Elsevier Science (USA). All rights reserved.
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