National Cancer Institute®
Last Modified: April 1, 2002
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. email@example.com
UI - 11740992
AU - Zierhut D; Bettscheider C; Schubert K; van Kampen M; Wannenmacher M
TI - Radiation therapy of stage I and II non-small cell lung cancer (NSCLC).
SO - Lung Cancer 2001 Dec;34 Suppl 3():S39-43
AD - Department of Clinical Radiology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. firstname.lastname@example.org
Surgery is the preferred and standard treatment for patients with resectable stage I and II non-small cell lung cancer (NSCLC). Survival rates of local surgery are unbeaten by other treatment modalities. Up to 70% of these patients survive 5 years or longer. However, there is a subset of patients who either are inoperable due to the presence of severe associated diseases, or who refuse surgery. In these patients radical radiotherapy with curative intent is an effective alternative. In our department we retrospectively analysed survival and freedom from treatment failure in those patients treated in our hospital with primary irradiation for stage I and II NSCLC (T1-2 N0-1 M0) during the last 20 years. In total 60 patients with a median age of 69 years could be evaluated. 35% had stage I and 65% had stage II NSCLC. All patients received 2- or 3-dimensionally planned megavoltage radiotherapy with a median dose of 60 Gy with normally fractionated single doses of 2.0 Gy five times a week. Pneumonitis WHO Grade III was found in 5 out of the 60 patients (8.3%). Locoregional recurrence was observed in 53% of the patients resulting in a median progression-free survival of 18 months and a median overall survival of 20.5 months. However, there is a need for further improvement of treatment outcome of radiotherapy for medically inoperable patients with early-stage NSCLC. One possibility might be radiation dose escalation or alteration in fractionation of radiotherapy, such as continuous hyperfractionated accelerated radiotherapy CHART or a modification thereof CHARTWEL. These new fractionation schemes might be beneficial for a subset of patients in terms of improved local control, reduced incidence of metastasis and improved long term survival. The combination of chemotherapy and radiotherapy might be another option for treatment of early-stage NSCLC. In advanced disease combined modality treatment turned out to be superior to radiotherapy alone, concerning local control and survival. If this is true also for early-stage NSCLC, it has to be shown in further investigations.
UI - 11740993
AU - Crino L; Cappuzzo F
TI - Multimodality therapy for non-small cell lung cancer (NSCLC): ongoing Italian experiences in the adjuvant and neoadjuvant settings.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S45-7
AD - Division of Medical Oncology, Bellaria Hospital, Via Altura 3, 40039 Bologna, Italy. email@example.com
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. firstname.lastname@example.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.
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. email@example.com
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.
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.
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. firstname.lastname@example.org
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.
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. email@example.com
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.
UI - 11803145
AU - Novello S; Le Chevalier T
TI - Use of chemo-radiotherapy in locally advanced non-small cell lung cancer.
SO - Eur J Cancer 2002 Jan;38(2):292-9
AD - Department of Medicine, Institut Gustave-Roussy, Rue Camille-Desmoulins, 94805 Villejuif Cedex, France.
Lung cancer is the leading cause of cancer mortality in the Western countries for both men and women. Approximately 40% of patients present with locally advanced and/or unresectable disease. While small improvements in outcome have occurred for this group of patients in the last decade, 5-year survival remains low, ranging from 5 to 20%. Distant metastases and loco-regional progression remain significant patterns of failure. Up to the late 1980s, the standard management for locally advanced non-small cell lung cancer (NSCLC) was conventional thoracic radiotherapy, but when treated with radiotherapy alone, less than 10% of patients survived for 5 years or more. 60-70% failed at distant sites and less than 20% achieved durable local control. The addition of chemotherapy reduces the rate of distant failure, improves survival and the combination of chemotherapy and radiotherapy has become the standard of care of patients with locally advanced NSCLC. Current developments aim to optimise individual components of combined modality schedules, increase their synergism and minimise toxicity.
UI - 11905734
AU - Saunders M I
TI - Programming of radiotherapy in the treatment of non-small-cell lung cancer--a way to advance care.
SO - Lancet Oncol 2001 Jul;2(7):401-8
AD - Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, UK. firstname.lastname@example.org
Radical radiotherapy, the mainstay of treatment for early inoperable non-small-cell lung cancer, is most commonly given in daily fractions, Monday to Friday, to a total dose of 60-70 Gy over 6-8 weeks. Since the 1980s, novel fractionation schedules have been explored with the aim of improving local tumour control and survival without increasing late morbidity. There have been two main approaches. In hyperfractionated radiotherapy the dose per fraction is reduced and the total dose increased to give improved tumour control without increased late morbidity. Hyperfractionation schedules, with more than one fraction per day have been successfully evaluated, but so far significant benefit has not been achieved when compared with conventional radiotherapy plus chemotherapy. In accelerated radiotherapy the overall duration of radiotherapy is reduced to overcome repopulation of tumour cells during the course of treatment. In all the different regimens of accelerated radiotherapy a common feature is giving two or more fractions on some or all treatment days and, in some cases, a lower dose per fraction is also incorporated. CHART (continuous hyperfractionated accelerated radiotherapy) is the most novel and accelerated schedule tested, and a randomised controlled trial showed a significant survival advantage from CHART compared with conventional radiotherapy. Changes in the fractionation of radiotherapy must be combined with other approaches such as neoadjuvant and concomitant chemotherapy, hypoxic-cell modifiers, and conformal radiotherapy, so that care of patients with non-small-cell lung cancer can be further advanced.
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.
UI - 11579109
AU - Bonner JA; Tincher SA; Fiveash JB
TI - Balancing the possible effectiveness of postoperative radiotherapy for non-small-cell lung cancer against the possible detriment of radiation-induced toxicity.
SO - J Clin Oncol 2001 Oct 1;19(19):3905-7
UI - 11579111
AU - Machtay M; Lee JH; Shrager JB; Kaiser LR; Glatstein E
TI - Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma.
SO - J Clin Oncol 2001 Oct 1;19(19):3912-7
AD - Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. email@example.com
PURPOSE: Some studies report a high risk of death from intercurrent disease (DID) after postoperative radiotherapy (XRT) for non-small-cell lung cancer (NSCLC). This study determines the risk of DID after modern-technique postoperative XRT. PATIENTS AND METHODS: A total of 202 patients were treated with surgery and postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III disease. Many patients (41%) had positive/close/uncertain resection margins. The median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was calculated actuarially and included patients who died of unknown/uncertain causes. Median follow-up was 24 months for all patients and 62 months for survivors. RESULTS: A total of 25 patients (12.5%) died from intercurrent disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4-year actuarial rate of DID was 13.5%. This is minimally increased compared with the expected rate for a matched population (approximately 10% at 4 years). On multivariate analysis, age and radiotherapy dose were borderline significant factors associated with a higher risk of DID (P =.06). The crude risk of DID for patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%) versus 17% for XRT dose > or = 54 Gy. The 4-year actuarial overall survival was 34%; local control was 84%; and freedom from distant metastases was 37%. CONCLUSION: Modern postoperative XRT for NSCLC does not excessively increase the risk of intercurrent deaths. Further study of postoperative XRT, particularly when using more sophisticated treatment planning and reasonable total doses, for carefully selected high-risk resected NSCLC is warranted.
UI - 11924237
AU - Moro D
TI - [Neoadjuvant treatment for early stages of non-small-cell lung carcinoma (NSCLC)]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S22-4
AD - Unite d'oncologie thoracique, CHU, Grenoble.
UI - 11924238
AU - Papadakis E
TI - [Adjuvant treatment for early stages of non-small-cell lung carcinoma (NSCLC)]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S25-8
AD - Service de pneumologie, Hopital Sotiria, Athenes.
UI - 11924239
AU - Mornex F
TI - [Therapeutic management of non-small-cell lung carcinoma (NSCLC) of stage III A]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S29-32
AD - Service d'oncologie, Hopital Jules Courmot, Lyon.
UI - 11924245
AU - Bonnette P
TI - [Lymph node excision in the surgical treatment of bronchopulmonary cancer]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S7-12
AD - Service de chirurgie thoracique, Hopital Foch, Suresnes.
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.
UI - 11882767
AU - Brabender J; Park J; Metzger R; Schneider PM; Lord RV; Holscher AH;
TI - Danenberg KD; Danenberg PV Prognostic significance of cyclooxygenase 2 mRNA expression in non-small cell lung cancer.
SO - Ann Surg 2002 Mar;235(3):440-3
AD - Department of Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, California, USA. firstname.lastname@example.org
OBJECTIVE: To investigate cyclooxygenase-2 (COX-2) mRNA expression in curatively resected non-small cell lung cancer (NSCLC) and to determine its association with prognosis. SUMMARY BACKGROUND DATA: Lung cancer is one of the most common malignancies in the world. Despite improvements in the diagnosis and treatment of NSCLC, the 5-year survival rate remains less than 15%. Identification of prognostic predictors based on molecular alterations could lead to additional diagnostic tools and eventually to more effective therapeutic options. Overexpression of COX-2 has been reported in several human malignancies, including lung cancer, but the prognostic importance of this overexpression has not been elucidated. METHODS: COX-2 mRNA expression was analyzed using a quantitative real-time polymerase chain reaction (Taqman) method in surgically resected tumor specimens from 89 patients with curatively resected NSCLC. RESULTS: COX-2 mRNA was detectable in all 89 (100%) tumor tissues. High COX-2 expression in tumors was significantly associated with inferior survival. Multivariate analysis showed that high COX-2 expression is an independent predictor of worse survival in patients with NSCLC. CONCLUSIONS: High COX-2 mRNA expression is an important biomarker for biologically aggressive disease in NSCLC and might be helpful in identifying patients who would benefit from additional therapies for controlling their disease.
UI - 11939670
AU - Wang CY; Hsie CC; Hsu HS; Wu YC; Hsu WH; Huang BS; Lin TC; Huang MH
TI - Pulmonary resection for metastases from colorectal adenocarcinomas.
SO - Zhonghua Yi Xue Za Zhi (Taipei) 2002 Jan;65(1):15-22
AD - Department of Surgery, Taipei Veterans General Hospital, Taiwan, ROC.
BACKGROUND: Colorectal cancer is one of the most common cancers in Taiwan, as in the other part of the world. Surgical intervention is the best treatment of choice, yet some patients still developed distant metastasis after primary lesions were controlled. Metastasectomy is reported to improve the survival. This retrospective study was carried out to evaluate the relationship between the prognostic factors of lung metastasectomy and patient survival. METHODS: From 1981 to 2000, 68 patients undergoing complete lung metastasectomy in our section were studied. The prognostic factors influencing survival were analyzed, and the survival analysis was made with Kaplan-Meier method and compared by log-rank test. RESULTS: There was no surgical mortality in our series. The 5-year survival was 36.1%. None of parameters such as age, sex, stage of primary colorectal cancer, surgical method, size, number of metastatic deposits and disease free interval showed to relate with the survival. CONCLUSIONS: We concluded that lung metastasectomy for colorectal cancer is safe and effective to improve the survival. Since there were no significant factors influencing the survival, there should be no absolute contraindication against resectable pulmonary metastasis after primary lesions were adequately controlled.
UI - 11804694
AU - Plataniotis GA; Kouvaris JR; Dardoufas C; Kouloulias V; Theofanopoulou
TI - MA; Vlahos L A short radiotherapy course for locally advanced non-small cell lung cancer (NSCLC): effective palliation and patients' convenience.
SO - Lung Cancer 2002 Feb;35(2):203-7
AD - Department of Radiation Oncology, Aristoteles University of Thessaloniki, AHEPA Hospital, 1 St. Kyriakidi str., Thessaloniki, 54636 Greece. email@example.com
In order to facilitate patients with symptomatic locally advanced NSCLC, especially those coming from remote areas we have employed two palliative RT schedules. The first (S1) is the well known from Medical Research Council (MRC) randomized studies 2 x 8.5 Gy one week apart and the second (S2) is a two-day RT schedule: three fractions of 4.25 Gy are given on the first day and two fractions of 4.25 Gy on the second day. The records of 92 patients were reviewed (48 for S1 and 44 for S2). Patients, disease characteristics and results were similar for both groups; rates of symptom disappearance were for S1 and S2, respectively: cough 24 and 20%, hemoptysis 60 and 67%, chest pain 57 and 64% and dyspnoea 55 and 45% The overall condition improved in 39 and 36%, respectively. The median palliation time in days was in S1 and S2, respectively: cough 70 and 66, haemoptysis 133 and 139, chest pain 68 and 62 and dyspnoea 74 and 69 days. The median survival was 25 weeks in both S1 and S2 groups (P=0.89 log-rank test). At 52 weeks (one year), ten (21%) and seven (16%) of the patients were alive in S1 and S2 groups, respectively. At 104 weeks, the corresponding figures were two (4%) and two (4.7%) for S1 and S2. Our results are in accordance to those reported in literature regarding the safety and efficacy of palliative hypofractionated radiotherapy schemes. Their use in selected patients could be cost-effective and convenient for patients especially those coming from remote areas.
UI - 11888009
AU - Van Houtte P
TI - The role of radiotherapy and the value of combined treatment in lung cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S91-8
AD - Institut J. Bordet, Department of Radiotherapy, Brussels, Belgium.
UI - 11917282
AU - Werner-Wasik M; Axelrod RS; Friedland DP; Hauck W; Rose LJ; Chapman AE;
TI - Grubbs S; Deshields M; Curran WJ Phase II: trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):34-9
AD - Kimmel Cancer Center of Jefferson Medical College, Philadelphia, PA, USA.
Twenty-four patients with non-small cell lung cancer received induction chemotherapy (paclitaxel, carboplatin) followed by concurrent thoracic irradiation (RT) and weekly paclitaxel. Acute esophagitis was scored weekly. Amifostine (AMI), 500 mg intravenously twice weekly, was added to the regimen in the second cohort of 12 patients. AMI was well tolerated. The incidence of grade 3 esophagitis was 18% in the initial 11 patients versus 9% in the AMI-treated patients. Mean esophagitis index (EI) was numerically lower in the AMI-treated patients than in the initial group (5.1 v 11.6, P =.14). The length of esophagus in the RT field was similar in both groups. Median survival time for all patients was 12.4 months. The EI, a novel measure of the severity and duration of acute esophagitis, may be reduced in lung cancer patients receiving AMI twice weekly with thoracic RT and paclitaxel. The effect of AMI was not caused by the shorter irradiated esophageal length. A phase III randomized trial is now open to assess the effect of AMI on esophagitis. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11917283
AU - Movsas B
TI - Exploring the role of the radioprotector amifostine in locally advanced non-small cell lung cancer: Radiation Therapy Oncology Group trial 98-01.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):40-5
AD - Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
The ultimate goal of any strategy in oncology is to enhance the therapeutic ratio, defined as tumor cell kill divided by normal tissue injury. Whereas most trials focus on intensifying therapy, this often increases toxicity so that there is no overall gain in the therapeutic ratio. Radiation Therapy Oncology Group (RTOG) trial 98-01, a phase III study testing the ability of a radioprotector (Amifostine [Ethyol, WR-2721]) to reduce the toxicity of an intensive chemoradiation regimen for locally advanced non-small cell lung cancer (NSCLC), is unique in that it addresses both "sides" of this equation. During the 1990s, thoracic radiotherapy (RT) combined with chemotherapy was accepted as a "new" gold standard for patients with good performance status locally advanced/inoperable NSCLC. This paradigm shift away from RT alone has raised several key questions: What is the optimal method of integrating chemotherapy and RT? Equally importantly, how can the toxicity of combined modality strategies be reduced? This article will review the background underlying RTOG 98-01, a trial exploring the potential role of amifostine in NSCLC. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11917284
AU - Komaki R; Lee JS; Kaplan B; Allen P; Kelly JF; Liao Z; Stevens CW;
TI - Fossella FV; Zinner R; Papadimitrakopoulou V; Khuri F; Glisson B; Pisters K; Kurie J; Herbst R; Milas L; Ro J; Thames HD; Hong WK; Cox JD Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):46-9
AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
A prospective randomized study was conducted to determine whether amifostine (Ethyol) reduces the rate of severe esophagitis and hematologic and pulmonary toxicity associated with chemoradiation or improves control of non-small cell lung cancer (NSCLC). Sixty patients with inoperable stage II or III NSCLC were treated with concurrent chemoradiotherapy. Both groups received thoracic radiation therapy (TRT) with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total dose 69.6 Gy. All patients received oral etoposide (VP-16), 50 mg Bid, 30 minutes before TRT beginning day 1 for 10 days, repeated on day 29, and cisplatin 50 mg/m(2) intravenously on days 1, 8, 29, and 36. Patients in the study group received amifostine, 500 mg intravenously, twice weekly before chemoradiation (arm 1); patients in the control group received chemoradiation without amifostine (arm 2). Patient and tumor characteristics were distributed equally in both groups. Of the 60 patients enrolled, 53 were evaluable (27 in arm 1, 26 in arm 2) with a median follow-up of 6 months. Median survival times were 26 months for arm 1 and 15 months for arm 2, not statistically significantly different. Morphine intake to reduce severe esophagitis was significantly lower in arm 1 (2 of 27, 7.4%) than arm 2 (8 of 26, 31%; P =.03). Acute pneumonitis was significantly lower in arm 1 (1 of 27, 3.7%) than in arm 2 (6 of 26, 23%; P =.037). Hypotension (20 mm Hg decrease from baseline blood pressure) was significantly more frequent in arm 1 (19 of 27, 70%) than arm 2 (1 of 26, 3.8%; P =.0001). Only 1 patient discontinued treatment because of hypotension. These preliminary results showed that amifostine significantly reduced acute severe esophagitis and pneumonitis. Further observation is required to assess long-term efficacy. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11917285
AU - Antonadou D
TI - Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):50-8
AD - Metaxas Cancer Hospital, Greece.
Radiotherapy (RT) or radiochemotherapy is the treatment of choice for patients with medically or technically inoperable non-small cell lung cancer (NSCLC) localized to the primary site and regional lymph nodes. Radiation-induced damage has been recognized as a major complication in thoracic RT. The use of concurrent chemoradiation has been associated with an increase in acute and late toxicity. Amifostine (Ethyol) is an effective cytoprotective agent and also may have a role in protecting healthy lung tissue during radiation treatment. The purpose of these 2 clinical trials was to investigate whether daily pretreatment with amifostine could reduce the incidence of esophagitis, and acute and late lung toxicity without affecting the antitumor efficacy of the treatment. The first was a phase III randomized trial of 146 patients with locally advanced lung cancer. All patients received conventional RT to a total of 55 to 60 Gy, and they were assigned randomly to pretreatment with 340 mg/m(2) of amifostine (A). Acute and late toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) grading system from grades 0 to 4. Ninety-seven patients were evaluated 2 months post-RT for the incidence of pneumonitis; 43% (23 of 53) of patients in the RT arm and 9% (9 of 44) in the A plus RT arm experienced grade > or = 2 pneumonitis (P <.001). Forty-nine percent (26 of 53) of patients in the RT arm and 16% (7/44) in the A plus RT arm showed changes that were representative of grade > or = 2 lung damage in the computed tomography (CT) scan. Fibrosis was present in 53% (19 of 36) of patients receiving RT versus 28% (9 of 32) in the A plus RT arm at 6 months (P < 0.05). The incidence of esophagitis grade > or = 2 during week 4 was 42% (31 of 73) in the RT arm versus 4% (3 of 73) in the A plus RT arm (P <.001). Among 97 patients evaluable for response 2 months after RT, complete or partial responses were present in 76% (40 of 53) of patients in the RT arm and 75% (33 of 44) in the A plus RT arm (P = 1.0). The second trial was a phase II randomized study of 45 patients with NSCLC. All patients had received platinum-based induction chemotherapy before being referred for conventional radiation treatment with or without A; a total dose of 55 to 60 Gy was administered at the primary site. Acute and late toxicities were evaluated and graded according the RTOG criteria from grades 0 to 4. Forty-five patients were evaluable for response 2 months after RT. Complete or partial responses were achieved in 78% (18 of 23) of patients in the RT arm and 82% (18 of 22) in the A plus RT arm (P =.278). By week 5, 74% (17 of 23) of patients in the RT group versus 36% (8 of 22) in the A plus RT group experienced grade > or = 2 esophagitis. (During the follow-up period, pulmonary toxicity was evaluated by CT scan.) Three months after RT, 65% (15/23) of patients in the RT group and 32% (7 of 22) in the A plus RT group presented with grade > or = 2 pneumonitis (P =.038). Amifostine reduces the incidence of acute and late radiation-induced toxicities. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11917286
AU - Arquette M; Wasserman T; Govindan R; Garfield D; Senzer N; Gillenwater
TI - H; Socinski M Phase II evaluation of amifostine as an esophageal mucosal protectant in the treatment of limited-stage small cell lung cancer with chemotherapy and twice-daily radiation.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):59-61
AD - Washington University, St Louis, MO 63110, USA.
For limited-stage small cell lung cancer, twice-daily radiation with concurrent chemotherapy improves survival rate, but has dose-limiting esophageal toxicity. The authors studied 34 patients treated with amifostine in an attempt to decrease the incidence and grade of esophagitis. The results indicate that there was no reduction in toxicity, but the authors were able to maintain the high complete response rate that had been reported previously. These results differ from the use of amifostine in non-small cell lung cancer in which there is the observation of esophageal protection. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11920642
AU - Chen JT; Chen YC; Wang YC; Tseng RC; Chen CY; Wang YC
TI - Alterations of the p16(ink4a) gene in resected nonsmall cell lung tumors and exfoliated cells within sputum.
SO - Int J Cancer 2002 Apr 10;98(5):724-31
AD - Department of Pathology, Taichung Veterans General Hospital, Republic of China.
Recently, we reported that p16 protein expression was nondetectable in 49.5% of 107 resected nonsmall cell lung cancers (NSCLCs), suggesting that the p16(INK4a) gene is frequently inactivated in primary NSCLC. To identify the molecular basis for this p16 immunohistochemical negativity further, we performed a genetic and epigenetic study of p16(INK4a) status in a series of 115 NSCLC samples parallel to the clinicopathologic and prognostic analyses. Microdissected tumor DNA samples were screened for homozygous deletion using comparative multiplex-polymerase chain reaction (PCR), for intragenic mutation using direct sequencing and for loss of heterozygosity (LOH) using an intragenic microsatellite marker, D9S942. Of these samples, 67 were further analyzed by SmaI-based PCR methylation assay to evaluate aberrant methylation at the gene. To examine the correlation of aberrant methylation in tumor and sputum samples, sputum samples from 12 matched patients were assessed for this change. We found that methylation of the p16(INK4a) gene was present in 38 of the 67 (56.7%) tumors and was significantly associated with negative p16 protein expression (p = 0.029). A 92% (11/12) concordance of sputum samples with matched resected tumors was found. The survival rates among adenocarcinoma patients with p16(INK4a) methylation were lower, but at a level of borderline significance compared with those patients without methylation (p = 0.071). In addition, 29.4% of the informative cases were found to harbor LOH at D9S942. None of the 115 microdissected tumors exhibited homozygous deletion in the p16(INK4a) gene. Only 1 patient exhibited a complex mutation at the fourth ankyrin repeat consensus sequence and concordantly demonstrated p16 immunohistochemical negativity. Overall, 69% (79/115) of NSCLC tumors had at least 1 type of p16(INK4a) alteration. Our data provide compelling evidence that p16(INK4a) alterations are involved in NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in p16(INK4a) deregulation. Copyright 2002 Wiley-Liss, Inc.
UI - 9053852
AU - Wolf G; Elez R; Doermer A; Holtrich U; Ackermann H; Stutte HJ;
TI - Altmannsberger HM; Rubsamen-Waigmann H; Strebhardt K Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer.
SO - Oncogene 1997 Feb 6;14(5):543-9
AD - Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt, Germany.
Our previous data indicate that the expression of the PLK gene which codes for a serine/threonine kinase is restricted to proliferating cells. In Northern blot experiments PLK mRNA expression was at the limit of detection in normal lung tissue but elevated in most samples of non-small cell lung cancer (NSCLC). A very low frequency of PLK transcripts was only found in bronchiolo-alveolar carcinomas. NSCLC patients whose tumors showed moderate PLK expression survived significantly longer (5 year survival rate=51.8%) than those with high levels of PLK transcripts (24.2%, P=0.001). No statistically significant correlation was found between PLK mRNA expression and age, sex, TNM status, histological type or degree of differentiation. Interestingly, the prognosis of patients in post-surgical stages I and II was correlated with PLK expression (5 year survival rates in stage I: 69.1% (moderate PLK) - 43.5% (high PLK), P=0.03 or in stage II: 51.9% (moderate PLK) - 9.9% (high PLK), P=0.006). These results suggest that PLK mRNA expression provides a new independent prognostic indicator for patients with NSCLC.
UI - 11373887
AU - Quddus AM; Kerr GR; Price A; Gregor A
TI - Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):95-8
AD - Western General Hospital, Edinburgh, UK.
The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction. Forty-two (69%) patients had a radiological complete response, 16 (26%) a partial response and the remainder stable disease. Clinically significant radiation pneumonitis occurred in one (2%) patient, radiation myelopathy in two (3%) and multiple rib fractures in one (2%). There did not appear to be an association between long-term survival and a radiosensitive phenotype. On univariate analysis, long-term survival was more frequent in patients receiving ten-fraction regimens than in those who underwent a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four (0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last review (median 10 years; range 5-17). We conclude that palliative thoracic radiotherapy produces long-term survival in 1.3% and personal cure in up to 1% of patients with advanced NSCLC.
UI - 11911271
AU - Xing T; Brattstrom D; Bergqvist M; Isaksson U; Wagenius G; Brodin O
TI - Radiation responsiveness of human lung cancer cell lines measured with a short term semiautomatic assay.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3925-8
AD - Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Sweden.
BACKGROUND: Fluorometric microculture cytotoxicity assay (FMCA) is a short-term semi-automatic method, based on dye-inclusion of surviving cells. The assay was developed for investigations of drug resistance on tumour cells from biopsy material. In the present study, this short-term assay was evaluated, regarding usefulness in determining radio-sensitivity. MATERIALS AND METHODS: Eight human lung cancer cell lines were used. There were five small cell lung cancer (SCLC and three non-small cell lung cancer (NSCLC cell lines. Results were compared with the corresponding data derived from the clonogenic assay and/or the extrapolation method. RESULTS: The surviving fraction (SF) after 2, 5 and 10 Gy compared with data from the clonogenic assay were not in accordance for 5 of the 8 cell lines. The FMCA assay overestimated SF- values for the SCLC cell lines. CONCLUSION: The FMCA assay is not useful as a quick screening method for the radioresponsiveness in vitro of human tumour cell lines.
UI - 11911293
AU - Mattern J; Volm M
TI - Clinical estimation of the growth rate of lung cancer.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4067-70
AD - German Cancer Research Center, Heidelberg. firstname.lastname@example.org
It is well known that the growth rate of lung tumors is closely related to prognosis and is an important determinant of responsiveness to therapy and curability. In this study, the velocity of tumor growth was calculated by dividing the area of the lesion at presentation divided by the time elapsed since symptoms were first noted. This parameter was applied to a group of patients with lung cancer and the predictive value of the velocity of tumor growth was assessed. Survival expectancy was found to be closely related to the growth rate of the tumors. The median survival time of patients with more slowly growing tumors was 102 weeks, while that of patients with fast-growing tumors was 30 weeks (log-rank test, p=0.00001). Linear regression analysis between velocity of tumor growth and tumor cell proliferation as measured by the PCNA-labelling index revealed a significant correlation between these two parameters. In conclusion, the velocity of a tumor measured in this way is an independent and significant prognostic factor for patients with lung cancer and may be used to non-invasively assess lung cancer proliferation in vivo, identifying rapidly growing tumors with poor prognosis that could benefit from a more aggressive therapy.
UI - 11911315
AU - Gridelli C; Curcio C; Iaffaioli R V; Brancaccio L; D'Aprile M; Gebbia V;
TI - Rossi A; Tortoriello A; Veltri E; Maione P; Barbarisi A; Gallo C; Guida C; Perrone F Carboplatin + epirubicin +VP-16 + lenograstim followed by radiotherapy + carboplatin as radiosensitizer in limited small cell lung cancer. A multicenter phase II study.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4179-83
AD - Oncologia Medica B, Istituto Nazionale Tumori, Napoli, Italy. email@example.com
A phase II trial was undertaken to test the activity and toxicity of carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1) + VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days 6 to 15) administered every 3 weeks for 4 cycles and subsequent chest irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line treatment of adults affected by limited small cel