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Abramson Cancer CenterNCI CANCERLIT® Search: Chemotherapy for Non-small Cell Lung Cancer - October 2002
National Cancer Institute®
Last Modified: October 1, 2002
- Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic
- Where to go with new expensive treatments in NSCLC.
- Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage
- [Randomized controlled trials in Japan--lung cancer]
- [Gemcitabine-based chemotherapy for non-small cell lung cancer (NSCLC)--a review of 30 randomized trials]
- [Outpatient chemotherapy for small cell lung cancer in our hospital]
- High-dose chemotherapy in small cell lung cancer.
- A Phase I-II study of sequential administration of topotecan and oral etoposide (toposiomerase I and II inhibitors) in the treatment of
- Phase II trial of irinotecan, paclitaxel and carboplatin in patients with previously untreated Stage IIIB/IV nonsmall cell lung carcinoma.
- A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer.
- Is long term gemcitabine useful in small cell lung cancer?
- Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant
- A phase II trial of gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma.
- Surprise phase III failure for ZD1839.
- Small cell lung cancer: defining a role for emerging platinum drugs.
- Predicting chemotherapy response to paclitaxel-based therapy in advanced non-small-cell lung cancer (stage IIIb or IV) with a higher T stage (>
- High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II
- Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer.
- Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET.
Table of Contents
1
UI - 9400948
AU - Ando M; Eguchi K; Shinkai T; Tamura T; Ohe Y; Yamamoto N; Kurata T;
TI -
Kasai T; Ohmatsu H; Kubota K; Sekine I; Hojo N; Matsumoto T; Kodama T;
Kakinuma R; Nishiwaki Y; Saijo N
Phase I study of sequentially administered topoisomerase I inhibitor
(irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic
non-small-cell lung cancer.
SO - Br J Cancer 1997;76(11):1494-9
AD - The Department of Medical Oncology, National Cancer Center Hospital,
Tokyo, Japan.
We conducted a phase I study of irinotecan (CPT-11) and etoposide
(VP-16) given sequentially to untreated patients with metastatic
non-small-cell lung cancer. Arm A: CPT-11 was given over 90 min on days
1-3 and VP-16 was given over 60 min on days 4-6. Arm B: VP-16 was given
on days 1-3 and CPT-11 on days 4-6. G-CSF was given to all patients
daily on days 7-17. Twenty-seven patients were entered randomly at the
two arms. The major dose-limiting toxicities in arms A and B were
granulocytopenia and diarrhoea. Transient elevations of transaminases
and bilirubin were observed in both arms. The degree of the toxicities
did not differ between the two arms. The maximum tolerated doses (MTDs)
were 60 mg m-2 CPT-11 and 60 mg m-2 VP-16 in both arms. Of the 13
patients who received more than two cycles, two out of five achieved
partial response (PR) at the first level of arm A and one out of four
achieved PR at the second level of arm B. We conclude that these
schedules of sequential CPT-11 and VP-16 administration were
inappropriate because of severe toxicities.
2
UI - 9683287
AU - Webb A; O'Brien ME
TI -
Where to go with new expensive treatments in NSCLC.
SO - Br J Cancer 1998 Jul;78(2):159-62
AD - Lung Unit, The Royal Marsden Hospital, Sutton, Surrey, UK.
3
UI - 11956647
AU - Mantovani G; Maccio A; Mulas C; Massa E; Madeddu C; Mura L; Contu P;
TI -
Versace R
Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus
medroxyprogesterone acetate and recombinant interleukin 2 in stage
IIIB-IV non-small cell lung cancer.
SO - Oncol Rep 2002 May-Jun;9(3):661-70
AD - Department of Medical Oncology, University of Cagliari, Italy.
mantovan@pacs.unica
The purpose of the study was to evaluate the effectiveness in terms of
response rates, toxicity and survival of the combination chemotherapy
regimen cisplatin and epidoxorubicin (epirubicin) including
medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and
antioxidants in patients with advanced (stage IIIB-IV) non-small cell
lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC
were enrolled in the study and 30 of them were evaluable. The mean age
of the patients was 61 years. Twenty (66.7%) out of 30 patients were
>or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG
performance status was 0 to 1 in 30 patients and 2 in 3 patients.
Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had
stage IV; histology was mainly squamous cell carcinoma (72.7%). The
treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40
mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day
subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally
and N-acetyl cysteine 1.8 g/day orally. The treatment was administered
for 6 weeks. Patients with a complete response (CR), partial response
(PR) or stable disease (SD) continued the treatment, according to
response re-evaluation, until 15 weeks. The present study reports the
results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients
were assessable for response: no CR was observed, a PR was achieved in
15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed
(ORR 30.0%). The median follow-up period was 13 months. The median
duration of response was 9 months. The median overall survival (OS) was
15 months. The one-year survival rate was 55.8%. The median
progression-free survival (PFS) was 10 months. The toxicity was, as
expected, mainly hematologic: neutropenia was the most significant
symptom. The non-hematologic toxicity was quite low. Therefore, the
treatment's toxicity was quite acceptable. There was no toxic death. The
30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study
are comparable with those observed with cisplatin plus epirubicin (ORR
39-54%) in phase II studies and in a previous phase III study (ORR 33%,
OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly
hematologic. Serum levels of proinflammatory cytokines significantly
decreased after treatment.
4
UI - 12355937
AU - Ichinose Y
TI -
[Randomized controlled trials in Japan--lung cancer]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1516-21
AD - Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1
Notame, Minami-ku, Fukuoka 811-1395, Japan.
Randomized controlled trials conducted in Japan were reviewed. Using
PubMed, 12 papers published after 1990 were selected. Six papers
presented at the annual meeting of the American Society of Clinical
Oncology from 1999 to 2002 were also added for use in this review.
According to the results of those trials, cisplatin plus either
irinotecan or docetaxel for advanced non-small cell lung cancer,
cisplatin plus irinotecan for small cell lung cancer and concurrent
chemoradiotherapy for a localized disease of both small and non-small
cell lung cancers have been established as standard treatments. No
adjuvant treatment method for resected patients has been proved to be
sufficiently effective.
5
UI - 12355944
AU - Fung MC; Sakata T; Ishiguro H; Adachi S
TI -
[Gemcitabine-based chemotherapy for non-small cell lung cancer
(NSCLC)--a review of 30 randomized trials]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1583-96
AD - Oncology Department, Lilly Research Laboratories-Japan, Eli Lilly Japan,
K. K.
Non-small cell lung cancer (NSCLC) represents a major challenge to
oncologists because of its dismal outcomes. Conventional cytotoxic
therapies for advanced disease have been unsatisfactory with modest
efficacy and high toxicities. The last decade witnessed the introduction
of many novel agents with enhanced efficacy and more manageable safety
profile than conventional therapies. Gemcitabine is one of these novel
agents which was introduced in the mid 1990's in the US/Europe and has
been available in Japan since 1999. Due to its unique profile of great
efficacy, mild toxicities and combinability with other agents,
gemcitabine and its combination have been widely accepted as one of the
standard regimens for the treatment of advanced NSCLC. There were
multiple clinical trials demonstrated the superiority of gemcitabine or
its combination over conventional therapies, especially in terms of
increased response, prolonged survival, and quality of life enhancement
for these patients. The current review presents an overview of all the
randomized clinical trials of gemcitabine and its combination for
advanced NSCLC published over the last decade.
6
UI - 12355957
AU - Minami S; Asai M; Iwahori K; Kouga K; Nishiyama A; Komuta K
TI -
[Outpatient chemotherapy for small cell lung cancer in our hospital]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1661-4
AD - Dept. of Respiratory Medicine, Osaka Police Hospital.
7
UI - 12195754
AU - Pasini F; Pelosi G; De Manzoni G; Rosti G
TI -
High-dose chemotherapy in small cell lung cancer.
SO - Tumori 2002 May-Jun;88(3):179-86
AD - Cattedra di Oncologia Medica, Universita di Verona, Italy.
Improvements in small cell lung cancer (SCLC) therapy with conventional
doses of drugs with or without radiotherapy have been poor, and the
5-year survival is discouraging. Since SCLC is highly sensitive to
radiotherapy and chemotherapy, some studies have tried to improve
survival by increasing the dose of the drugs. Within conventional
ranges, dose intensity can be increased with the support of
hematopoietic growth factors (G/GM-CSF) and/or shortening treatment
intervals (e.g. weekly regimens). However, dose intensity could be
increased by only 20-30% and a survival advantage was not definitively
obtained. Given its high chemosensitivity already two decades ago, SCLC
was one of the first malignancies deemed suitable for maximizing dose
and dose intensity with the support of autologous bone marrow
transplantation (ABMT). On the whole, results were disappointing and the
procedure was nearly abandoned. Nowadays, some interest is emerging
again due to the improvements in supportive care such as the
availability of hematopoietic growth factors and the peripheral blood
progenitor cells (PBPC).
8
UI - 12237920
AU - Mok TS; Wong H; Zee B; Yu KH; Leung TW; Lee TW; Yim A; Chan AT; Yeo W;
TI -
Chak K; Johnson P
A Phase I-II study of sequential administration of topotecan and oral
etoposide (toposiomerase I and II inhibitors) in the treatment of
patients with small cell lung carcinoma.
SO - Cancer 2002 Oct 1;95(7):1511-9
AD - Department of Clinical Oncology, The Chinese University of Hong Kong,
Hong Kong, China. mok206551@cuhk.edu.hk
BACKGROUND: Topotecan (9-dimethylaminomethyl-10-hydroxycampthothecin) is
a new topoisomerase I inhibitor with promising efficacy in the treatment
of patients with small cell lung carcinoma (SCLC). Combination with a
topoisomerase II inhibitor may potentate the therapeutic effect of
topotecan, although there has been conflicting preclinical information
on the combination. The objectives of this study were to establish the
maximum tolerated dose and to determine the efficacy of the sequential
combination of intravenous topotecan and oral etoposide in the treatment
of patients with SCLC. METHODS: Patients with histologically confirmed,
limited or extensive stage SCLC were eligible. The dose escalation
scheme of three cohorts (six patients per cohort) started at intravenous
topotecan 0.5 mg/m(2) per day for 5 days and oral etoposide 50 mg twice
daily for 7 days (21-day cycles). Subsequent dose levels involved
escalation of topotecan to 0.75 mg/m(2) per day and 1.0 mg/m(2) per day
for 5 days. A Phase II study was conducted at one dose level below the
maximum tolerated dose. The authors alternated the drug sequence with
each consecutive cycle and compared the hematologic toxicity between the
two sequences. RESULTS: Thirty-six patients (21 patients with limited
disease and 15 patients with extensive disease) received a total of 173
courses of sequential combination chemotherapy (topotecan --> etoposide,
88 courses; etoposide --> topotecan, 85 courses). The authors identified
dose levels for the Phase II study as follows: topotecan, 0.75 mg/m(2)
per day for 5 days; and etoposide, 50 mg twice daily for 7 days. The
dose-limiting toxicity was neutropenia. At this dose level, the
incidence of Grade 3-4 neutropenia and the incidence of Grade 3-4
thrombocytopenia were 25% and 10.9%, respectively. Two patients died
from neutropenic sepsis. There was no significant difference in
hematologic toxicities between the two sequences. Complete and partial
response rates were 5.6% and 55.6%, respectively (limited disease, 9.5%
and 66.75%; extensive disease, 0% and 40%, respectively). The median
progression free survival was 31.9 weeks (limited disease, 36.1 weeks;
extensive disease, 28.9 weeks; 95% confidence interval, 25.6-36.0
weeks), and the median overall survival was 52.4 weeks (limited disease,
54.9 weeks; extensive disease, 30.1 weeks; 95% confidence interval,
39.6-57.7 weeks). CONCLUSIONS: Combination therapy with topoisomerase I
and II inhibitors is a safe and effective regimen for patients with
SCLC. Future research on this combination should focus on an oral
regimen for patients with extensive disease and poor tolerance to
cisplatin. The authors recommend an oral dosage of topotecan at 1.2
mg/m(2) per day (equivalent to intravenous topotecan at 0.75 mg/m(2) per
day) for 5 days followed by etoposide 50 mg twice daily for 7 days.
Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10836
9
UI - 12237921
AU - Socinski MA; Sandler AB; Israel VK; Gillenwater HH; Miller LL; Locker
TI -
PK; Antonellini A; Elfring GL; Natale RB
Phase II trial of irinotecan, paclitaxel and carboplatin in patients
with previously untreated Stage IIIB/IV nonsmall cell lung carcinoma.
SO - Cancer 2002 Oct 1;95(7):1520-7
AD - Multidisciplinary Thoracic Oncology Program, University of North
Carolina, Chapel Hill, North Carolina 27599, USA. socinski@med.unc.edu
BACKGROUND: This Phase II multicenter, open-label, single-arm study
evaluated the efficacy and safety of a three-drug combination of
irinotecan (CPT-11), paclitaxel, and carboplatin in advanced nonsmall
cell lung carcinoma (NSCLC). METHODS: Patients received repeated 21-day
cycles at starting doses of paclitaxel 175 mg/m(2) administered over 3
hours, followed by carboplatin AUC of 5 over 30 minutes and CPT-11 at a
starting dose level of 100 mg/m(2) over 90 minutes, all given on the
first day of each cycle. Patients were evaluated for objective tumor
response, time to tumor progression (TTP), survival, and safety.
RESULTS: Forty patients were enrolled. Baseline patient characteristics
included: median age 58 years (range, 32-79); 23 males and 17 females;
performance status of 0 (21 patients), 1 (18 patients), or 2 (1
patient); and Stage IIIB (10 patients) and Stage IV (30 patients)
disease. A median of six cycles (range, one to eight) were administered.
Grade 3-4 toxicities observed in >/= 10% of the patients included
neutropenia (78%), asthenia (20%), diarrhea (20%), nausea (18%),
vomiting (13%), anemia (10%), and dyspnea (10%). Febrile neutropenia
occurred in eight patients (20%), with one death due to neutropenic
sepsis. Twelve of 38 evaluable patients had confirmed tumor responses
(32%), while 21 (55%) had stable disease (including 12 patients [32%]
with minor responses). Only 13% had disease progression at their initial
tumor assessment. The median TTP and survival were 5.3 months (range,
0.03-6.2 months) and 12.5 months (range 0.3-28.6+ months), respectively.
The one and two year survival probabilities were 0.50 (95% confidence
interval [CI], 0.28-0.73) and 0.21 (95% CI, 0.0-0.67), respectively.
CONCLUSIONS: The combination of CPT-11, paclitaxel, and carboplatin can
be safely administered and is active in the treatment of advanced NSCLC.
Based on the favorable survival outcome, this regimen is undergoing
evaluation in prospective randomized trials. Copyright 2002 American
Cancer Society.DOI 10.1002/cncr.10852
10
UI - 12006520
AU - Hahn SM; Bernhard EJ; Regine W; Mohiuddin M; Haller DG; Stevenson JP;
TI -
Smith D; Pramanik B; Tepper J; DeLaney TF; Kiel KD; Morrison B; Deutsch
P; Muschel RJ; McKenna WG
A Phase I trial of the farnesyltransferase inhibitor L-778,123 and
radiotherapy for locally advanced lung and head and neck cancer.
SO - Clin Cancer Res 2002 May;8(5):1065-72
AD - Department of Radiation Oncology, University of Pennsylvania School of
Medicine, Philadelphia 19104-4283, USA. hahn@xrt.upenn.edu
PURPOSE: Preclinical data have demonstrated that
farnesyltransferaseinhibitors (FTIs) are radiation sensitizers in
selected cell lines. The objective of this Phase I trial was to
determine the maximally tolerated dose of the FTI L-778,123 in
combination with radiotherapy in non-small cell lung cancer (NSCLC) and
head and neck cancer (HNC). EXPERIMENTAL DESIGN: L-778,123 was given by
continuous i.v. infusion and dose escalated in conjunction with standard
radiotherapy. The presence of a ras mutation was not required for study
entry. RESULTS: Nine patients (six NSCLC patients and three HNC
patients) were enrolled on two dose levels of FTI. No dose-limiting
toxicities were observed at the first dose level of 280 mg/m2/day during
weeks 1, 2, 4, and 5 of radiotherapy. One episode of dose-limiting
toxicity, grade IV neutropenia, was observed in one of three patients
treated at 560 mg/m2/day during weeks 1, 2, 4, 5, and 7. No episodes of
dose-limiting mucositis, esophagitis, or pneumonitis were observed. Of
the four patients with NSCLC with evaluable disease, three patients had
a complete response to treatment and one patient had a partial response.
A complete clinical response to treatment was observed in two patients
with HNC. In vitro studies in tumor cells obtained from a NSCLC patient
on this trial showed radiosensitization with FTI and that tumor cells
accumulated in G2-M after L-778,123 treatment. CONCLUSIONS: The
combination of L-778,123 and radiotherapy at dose level 1 is associated
with acceptable toxicity. Local responses have been observed in four
NSCLC patients without a clear increase in radiotherapy-associated
toxicities.
11
UI - 11955659
AU - Dediu M
TI -
Is long term gemcitabine useful in small cell lung cancer?
SO - Lung Cancer 2002 May;36(2):217-8
12
UI - 12377962
AU - Vokes EE; Herndon JE 2nd; Crawford J; Leopold KA; Perry MC; Miller AA;
TI -
Green MR
Randomized phase II study of cisplatin with gemcitabine or paclitaxel or
vinorelbine as induction chemotherapy followed by concomitant
chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and
leukemia group B study 9431.
SO - J Clin Oncol 2002 Oct 15;20(20):4191-8
AD - University of Chicago Medical Center and Cancer and Leukemia Group B,
Chicago, IL, USA. evokes@medicine.bsd.uchicago.edu
PURPOSE: To evaluate new drugs in combination with cisplatin in
unresectable stage III non-small-cell lung cancer, Cancer and Leukemia
Group B (CALGB) conducted a randomized phase II study of two cycles of
induction chemotherapy followed by two additional cycles of the same
drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible
patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22,
43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and
29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225
mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64;
and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15
mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43
at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five
eligible patients were analyzed. Toxicities during induction
chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade
3 or 4 toxicities during concomitant chemoradiotherapy consisted of
thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates
after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2,
and 3, respectively. Median survival for all patients was 17 months.
One-, 2-, and 3-year survival rates for the patients on the three arms
were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles
of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin
can be administered at these doses and schedules. The observed survival
rates exceed those of previous CALGB trials and may be attributable to
the use of concomitant chemoradiotherapy. Induction chemotherapy added
to concomitant chemoradiotherapy is being evaluated in a phase III
randomized trial.
13
UI - 12365019
AU - Popa IE; Stewart K; Smith FP; Rizvi NA
TI -
A phase II trial of gemcitabine and docetaxel in patients with
chemotherapy-naive, advanced nonsmall cell lung carcinoma.
SO - Cancer 2002 Oct 15;95(8):1714-9
AD - Lombardi Cancer Center, Georgetown University Medical Center,
Washington, DC, USA.
BACKGROUND: The goals of the current study were to determine the safety
and efficacy of a nonplatinum-containing doublet, gemcitabine and
docetaxel, in the treatment of patients with chemotherapy-naive nonsmall
cell lung carcinoma (NSCLC). METHODS: Thirty-two patients with advanced,
chemotherapy-naive NSCLC were treated with gemcitabine (1000 mg/m(2))
and docetaxel (40 mg/m(2)) administered on Days 1 and 8 every 21 days.
All patients were evaluable for toxicity and survival and 27 patients
were evaluable for response. RESULTS: This combination was extremely
well tolerated with Grade 3 or 4 neutropenia occurring in 6 of 32
patients (19%) (grading was based on the National Cancer Institute
Common Toxicity Criteria). There were two episodes of Grade 3
thrombocytopenia and no episodes of Grade 3 or 4 anemia. Grade 3 or 4
nonhematologic toxicities included nausea (occurring in 1 of 32
patients), diarrhea (occurring in 1 of 32 patients), fatigue (occurring
in 10 of 32 patients), fluid retention (occurring in 2 of 32 patients),
anorexia (occurring in 4 of 32 patients), and transaminitis (occurring
in 2 of 32 patients). Six patients experienced Grade 3 pneumonitis that
was at least possibly related to the combination of gemcitabine and
docetaxel. There was 1 complete response and 7 partial responses for an
overall response rate of 30%. The 1-year and median survivals were 35%
and 7.9 months, respectively. CONCLUSIONS: In the current study, the
regimen of gemcitabine (1000 mg/m(2)) and docetaxel (40 mg/m(2))
administered on Days 1 and 8 every 21 days was well tolerated with
manageable hematologic and nonhematologic toxicities. The responses were
comparable to those achieved with platinum-based combination
chemotherapy and the 2-year survival was an encouraging 19%. These data
would support the further study of this nonplatinum doublet in patients
with advanced NSCLC. Copyright 2002 American Cancer Society.
14
UI - 12372708
AU - Wilkinson E
TI -
Surprise phase III failure for ZD1839.
SO - Lancet Oncol 2002 Oct;3(10):583
15
UI - 12239444
AU - Schiller JH
TI -
Small cell lung cancer: defining a role for emerging platinum drugs.
SO - Oncology 2002;63(2):105-14
AD - University of Wisconsin Hospital, Madison, 53792, USA.
jhschill@facstaff.wisc.edu
Small cell lung cancer (SCLC) is characterized by early dissemination
and a rapid, aggressive clinical course. It has, however, marked
susceptibility to both chemotherapy and radiotherapy, although treatment
is complicated by the fact that SCLC tumors invariably develop
resistance to multiple chemotherapeutic agents. Local therapy is rarely
of benefit in SCLC because three-quarters of patients present with
metastatic disease and many of the remaining patients are thought to
have micrometastatic disease. Chemotherapy is, therefore, the
cornerstone of treatment. Of the many combination regimens used,
etoposide/cisplatin or etoposide/carboplatin have emerged as the
regimens of choice because they offer a good therapeutic index and can
be combined with radiotherapy. Response to second-line therapy remains
consistently poor. As the prototype platinum compound, cisplatin has
played a major role in the management of SCLC. Although its exact
contribution to the treatment of SCLC has been difficult to ascertain, a
recent meta-analysis reported a significant 1-year survival advantage of
approximately 4% with cisplatin-containing regimens versus regimens
without. However, cisplatin is characterized by several serious adverse
events and, like other chemotherapeutic agents, is eventually rendered
ineffective against SCLC because of acquired resistance. Several new
platinum formulations or compounds are showing promising activity in
SCLC. The impetus for their development has been to circumvent cisplatin
resistance or to improve upon the toxicity profile of cisplatin. If the
early promise shown by these compounds is confirmed in the clinic, they
may offer a new approach to the treatment of SCLC, including recurrent
disease for which limited treatment options are currently available.
Copyright 2002 S. Karger AG, Basel
16
UI - 12239453
AU - Hsu WH; Yen RF; Kao CH; Shiun SC; Hsu NY; Lin CC; Lee CC
TI -
Predicting chemotherapy response to paclitaxel-based therapy in advanced
non-small-cell lung cancer (stage IIIb or IV) with a higher T stage (>
T2). Technetium-99m methoxyisobutylisonitrile chest single photon
emission computed tomography and P-glycoprotein express ion.
SO - Oncology 2002;63(2):173-9
AD - Division of Pulmonary/Critical Care Medicine, Department of Medicine,
China Medical College Hospital, Taichung, Taiwan.
OBJECTIVE: The aim of this study was to compare technetium-99m
methoxyisobutylisonitrile (Tc-MIBI) chest single photon emission
computed tomography (SPECT) results, immunohistochemical analyses of
P-glycoprotein (Pgp) expression and response to paclitaxel in
non-small-cell lung cancer (NSCLC). METHODS: Before chemotherapy with
paclitaxel, 30 patients with stage IIIb or IV NSCLC were enrolled in
this study. Early chest SPECT was performed 10 min after intravenous
injection of Tc-MIBI. Tc-MIBI chest SPECT images were qualitatively
interpreted. Early tumor-to-normal lung ratios (T/NL) were calculated
quantitatively. Immunohistochemical analyses were performed on multiple
nonconsecutive sections of the biopsy specimens to determine Pgp
expression. Chemotherapy response was evaluated in the third month after
completion of treatment by clinical and radiological methods. RESULTS:
All 15 (100%) cases with good response and negative Pgp expression had
positive results of early Tc-MIBI chest SPECT. Ten of 15 (67%) cases
with poor response and positive Pgp expression had negative results of
early Tc-MIBI chest SPECT. These early T/NL ratios (3.3 +/- 0.8 for the
15 patients with good response and 2.0 +/- 0.2 for the 5 patients with
poor response) in lung cancer could be detected on early Tc-MIBI chest
SPECT. The difference was significant (p < 0.05) by an independent
Student t test. However, no significant differences were found for other
prognostic factors (age, sex, body weight loss, performance status,
tumor cell type, and tumor stage) between the good and poor response
groups. CONCLUSION: Early Tc-MIBI chest SPECT can be used to understand
the Pgp expression in NSCLC and to quickly predict chemotherapy response
to paclitaxel. Copyright 2002 S. Karger AG, Basel
17
UI - 12243807
AU - Rosenman JG; Halle JS; Socinski MA; Deschesne K; Moore DT; Johnson H;
TI -
Fraser R; Morris DE
High-dose conformal radiotherapy for treatment of stage IIIA/IIIB
non-small-cell lung cancer: technical issues and results of a phase I/II
trial.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):348-56
AD - Department of Radiation Oncology, Lineberger Comprehensive Cancer Center
of the University of North Carolina--University of North Carolina at
Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
rosenman@radonc.unc.edu
PURPOSE: We completed a Phase I/II clinical trial (Lineberger
Comprehensive Cancer Center 9603), in which we treated 62 Stage
IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with
two cycles of induction carboplatin/paclitaxel chemotherapy, followed by
concurrent weekly carboplatin/paclitaxel with radiation doses escalated
from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate
of 38%, and the high dose of radiation used justified a critical
analysis of the technical and clinical components of this trial. METHODS
AND MATERIALS: Between 1996 and 1999, 62 sequential patients with
inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two
cycles of induction carboplatin (area under the concentration curve = 6
using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an
escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly
(area under the concentration curve = 2) and paclitaxel weekly (45
mg/m(2)). The goals of the trial were to determine whether 74 Gy of
radiation could be safely delivered under these circumstances and
whether patients could potentially benefit in terms of survival. The
radiation treatment plans for all 62 patients were reviewed to determine
the prechemotherapy and postchemotherapy tumor volume, as well as the
dose-volume histograms of the normal lung and esophagus. RESULTS: Of the
62 patients who entered the trial, 48 completed the entire course of
treatment. At last follow-up, 20 patients were alive (crude survival
rate 32%). With a median follow-up of 43 months, the median survival was
24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox
regression analysis showed that survival was best predicted by whether
the patient had received radiotherapy (finished the trial), performance
status, disease stage, and log postchemotherapy tumor volume. The 3-year
survival rate for the 48 patients finishing the trial was 45%. Eight
patients (13%) suffered locoregional relapse as the only site of
failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients
(8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40
(65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be
predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION:
Radiation doses of 74 Gy, when given under the guidelines of the
Lineberger Comprehensive Cancer Center 9603, appear to be safe and may
possibly contribute to increased survival in patients with inoperable
Stage IIIA/IIIB NSCLC.
18
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
UI - 12243810
AU - Schild SE; Stella PJ; Geyer SM; Bonner JA; Marks RS; McGinnis WL; Goetz
TI -
SP; Kuross SA; Mailliard JA; Kugler JW; Schaefer PL; Jett JR
Phase III trial comparing chemotherapy plus once-daily or twice-daily
radiotherapy in Stage III non-small-cell lung cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):370-8
AD - Mayo Clinic and Mayo Foundation, Rochester, MN, USA. sschild@mayo.edu
PURPOSE: This Phase III study was performed to determine whether
chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior
survival for patients with Stage III non-small-cell lung cancer (NSCLC).
METHODS AND MATERIALS: Patients with Stage III NSCLC and an Eastern
Cooperative Oncology Group performance status of
UI - 12368367
AU - Hoekstra CJ; Hoekstra OS; Stroobants SG; Vansteenkiste J; Nuyts J; Smit
TI -
EF; Boers M; Twisk JW; Lammertsma AA
Methods to monitor response to chemotherapy in non-small cell lung
cancer with 18F-FDG PET.
SO - J Nucl Med 2002 Oct;43(10):1304-9
AD - Clinical PET Centre, VU University Medical Centre, Amsterdam, The
Netherlands.
PET using 18F-FDG is a promising technique to monitor response in
oncology. Unfortunately, a multitude of analytic methods is in use. To
date, it is not clear whether simplified methods could replace complex
quantitative methods in routine clinical practice. The aim of this study
was to select those methods that would qualify for further assessment in
a future prospective response-monitoring study by comparing results with
patient outcome. METHODS: Dynamic 18F-FDG PET scans were obtained on 2
groups of patients. First, 10 patients with advanced non-small cell lung
cancer (NSCLC) were scanned on consecutive days before treatment to
assess test-retest variability. Second, 30 scans were obtained on 19
patients with locally advanced NSCLC as part of an ongoing
response-monitoring study. These scans were analyzed by 2 observers to
assess observer variability. In addition, these studies were used to
compare various methods with the gold standard, full kinetic analysis
(nonlinear regression [NLR]). RESULTS: Using an image-derived input
function, NLR showed excellent test-retest and observer agreement
confirming that it could be used as a gold standard method. From a total
of 34 analytic methods, 10 showed good correlation with NLR. Taking into
account the degree of complexity of the methods, 4 remain for further
evaluation. CONCLUSION: The optimal method for analysis of 18F-FDG PET
data was determined for several levels of complexity. Four methods need
to be evaluated further to determine the optimal trade-off between
simplicity and accuracy for routine clinical practice.
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