National Cancer Institute®
Last Modified: May 1, 2002
UI - 11764664
AU - Nestle U; Hellwig D; Fleckenstein J; Walter K; Ukena D; Rube C; Kirsch
TI - CM; Baumann M Comparison of early pulmonary changes in 18FDG-PET and CT after combined radiochemotherapy for advanced non-small-cell lung cancer: a study in 15 patients.
SO - Front Radiat Ther Oncol 2002;37():26-33
AD - Department of Nuclear Medicine, University Hospital of the Saarland, Homburg/Saar, Germany. email@example.com
UI - 11784874
AU - Noda K; Nishiwaki Y; Kawahara M; Negoro S; Sugiura T; Yokoyama A;
TI - Fukuoka M; Mori K; Watanabe K; Tamura T; Yamamoto S; Saijo N; The Japan Clinical Oncology Group Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.
SO - N Engl J Med 2002 Jan 10;346(2):85-91
AD - Kanagawa Cancer Center, Yokohama, Japan.
BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. METHODS: We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. RESULTS: The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. CONCLUSIONS: Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.
UI - 11935300
AU - Vogt U; Zaczek A; Klinke F; Granetzny A; Bielawski K; Falkiewicz B
TI - p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer.
SO - J Cancer Res Clin Oncol 2002 Mar;128(3):141-7
AD - European Laboratory Association Section Ibbenburen, Roggenkampstrasse 10, 49477 Ibbenburen, Germany.
PURPOSE: About 40% of non-small cell lung cancer (NSCLC) patients are candidates for systemic chemotherapy, despite the fact that at diagnosis most NSCLC are usually chemoresistant both in vivo and ex vivo. It is important to develop sufficient methods of prediction of the response to chemotherapy and to find molecular markers that may prognose this response. Therefore, a study on the relationship of p53gene status to the ex vivo chemosensitivity of primary human NSCLC was performed. METHODS: Three drug combinations (carboplatin/etoposide, cyclophosphamide/etoposide/epirubicin, and paclitaxel/carboplatin) were tested in a modified ATP cell viability assay. A group of 28 cases of primary human NSCLC was assessed. RESULTS: Ex vivo chemosensitivity testing showed that tumors with p53 mutations were significantly more resistant to the cyclophosphamide/etoposide/epirubicin regimen than with normal p53 gene ( P = 0.012). However, no correlation was observed for two other treatment regimens. CONCLUSION: Mutations in the p53gene can lead to enhanced chemoresistance, confirming the hypothesis that the p53 gene may serve as a marker of tumor response to treatment in NSCLC. However, the data also illustrate that some additional factors might contribute to drug resistance of the examined tumors.
UI - 11986422
AU - Ando Y; Figg WD
TI - Irinotecan in small-cell lung cancer.
SO - N Engl J Med 2002 May 2;346(18):1414-5; discussion 1414-5
UI - 11884052
AU - Muller H
TI - Combined regional and systemic chemotherapy for advanced and inoperable non-small cell lung cancer.
SO - Eur J Surg Oncol 2002 Mar;28(2):165-71
AD - Department of Oncologic Surgery, Carl von Hess Hospital, Hammelburg, Germany. H.Mueller@Klinik-Hammelburg.de
AIMS: The objective was to establish the feasibility and toxicity of regional chemotherapy using an isolated thoracic perfusion (ITP) technique plus low dose systemic chemotherapy as induction chemotherapy followed by surgery in advanced non-small cell lung cancer (NSCLC). METHODS: twenty-two chemotherapy-naive patients with NSCLC (median age of 57 years, stage III-IV disease with metastases only in the thoracic region, Karnofsky index >60), received two cycles of regional plus systemic chemotherapy with a treatment-free interval of 4 weeks. The cytostatic regimen consisted of 10 mg/m(2) mitomycin, 25 mg/m(2) navelbine and 30 mg/m(2) cisplatin during ITP followed by low-dose systemic chemotherapy with 250 mg/m(2) 5-fluorouracil and 20 mg/m(2) cisplatin given as a continuous infusion on day 1-4. Patients were re-evaluated for response and surgery was carried out if possible. RESULTS: All 22 patients could be assessed for toxicity, response and survival. There were 19/22 remissions corresponding to a regression rate of 86.4%; 16/22 patients could be resected. This corresponded to a resectability rate of 72.7% (13 complete resections R0, 1 R1, 2 R2). Side-effects were transient and acceptable with no treatment- or surgery-related deaths. Median survival has not been reached after an observation time of 15 months. The estimated 1-year survival rate was 67.3%. CONCLUSIONS: Regional chemotherapy using an ITP application form is highly effective in advanced NSCLC stage III-IV leading to a high rate of resectability with an encouraging survival outcome. Copyright Harcourt Publishers Limited.
UI - 11955727
AU - Bradley JD; Scott CB; Paris KJ; Demas WF; Machtay M; Komaki R; Movsas B;
TI - Rubin P; Sause WT A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04).
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1173-9
AD - Radiation Oncology Center, Washington University Medical Center, St. Louis, MO 63110, USA. firstname.lastname@example.org
PURPOSE: The results of Phase I/II data testing beta-interferon with radiation therapy in a non-small-cell lung cancer population were promising. Based on these data, the Radiation Therapy Oncology Group (RTOG) initiated a Phase III trial to test the efficacy of beta-interferon in poor-risk patients with Stages IIIA and IIIB 1998, 123 patients were accrued to this trial. Enrolled patients were not eligible for other chemoradiation studies within the RTOG. Eligibility criteria included histologically confirmed Stage IIIA or IIIB non-small-cell lung cancer (according to American Joint Committee on Cancer) considered clinically inoperable or unresectable at the time of surgery. Patients were required to have a Karnofsky performance status 50-70 or >70 and at least 5% weight loss over the preceding 3 months. Betaseron (recombinant human interferon beta(ser), rHuIFN-beta(ser),) was the chosen preparation of beta-interferon. The patients randomized to the investigational arm received 16 x 10(6) IU of Betaseron by i.v. bolus given 3 days a week (Monday-Wednesday) on Weeks 1, 3, and 5. The Betaseron was given 30 minutes before radiation therapy for a total of nine doses. Irradiation was delivered at 2 Gy per fraction, 5 days a week, for a total of 60 Gy over 6 weeks and was identical for both arms. The primary end point of the trial was overall survival with local control as a secondary end point. Toxicities occurring within 90 days of therapy completion were defined as acute. RESULTS: The median follow-up was 4 years (range: 2.5-6 years) for surviving patients. Seventy-six percent of all patients completed beta-interferon. Toxicity was the primary reason for noncompliance. Radiotherapy (RT) compliance was excellent in the RT-alone arm, with 94% completing therapy, compared to 82% in the beta-interferon arm (p = 0.0475). Grade 3 and 4 acute toxicities were higher on the beta-interferon arm (p = 0.0249). Grade 3 and 4 acute toxicities were primarily related to lung (n = 8) and esophagus (n = 7). No Grade 4 or 5 late toxicities were seen for patients in the radiation-alone arm. However, three patients on the beta-interferon arm experienced Grade 4 toxicity, and one patient died. The 1-year survival rate for the RT-alone arm was 44% with a median survival time of 9.5 months. The 1-year survival on the beta-interferon arm was 42% with a median survival of 10.3 months. There was no statistical difference in survival times (p = 0.66). CONCLUSIONS: This multicenter, controlled Phase III trial failed to confirm the efficacy of Betaseron in patients receiving definitive radiotherapy for locally advanced, nonmetastatic non-small-cell lung cancer. The use of beta-interferon led to greater rates of both acute and late treatment-related toxicity. The RTOG continues to investigate other biologic modifiers that may provide a nontoxic alternative for this poor-risk population.
UI - 11784875
AU - Schiller JH; Harrington D; Belani CP; Langer C; Sandler A; Krook J; Zhu
TI - J; Johnson DH; The Eastern Cooperative Oncology Group Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
SO - N Engl J Med 2002 Jan 10;346(2):92-8
AD - University of Wisconsin Hospital and Clinics, Madison, USA.
BACKGROUND: We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer. METHODS: A total of 1207 patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel.RESULTS: The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3, 4, or 5 renal toxicity (in 9 percent of patients, vs. 3 percent of those treated with cisplatin plus paclitaxel). Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1. CONCLUSIONS: None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer.
UI - 12000824
AU - Locke I; Gillham CM
TI - Chemotherapy for lung cancer.
SO - N Engl J Med 2002 May 9;346(19):1498; discussion 1498
UI - 11989910
AU - Gridelli C; Ferrara C; Del Gaizo F; Guerriero C; Nicolella D; Colantuoni
TI - G; Rossi A Chemotherapy of advanced NSCLC in the elderly.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S143-4
AD - Divisione di Oncologia Medica, Azienda Ospedaliera SG Moscati, Avellino.
UI - 11989911
AU - Paccagnella A; Oniga F; Favaretto A; Biason R; Ghi MG
TI - Elderly patients with small cell lung cancer.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S145-7
AD - Oncology Unit, Venice Hospital.
UI - 11989921
AU - Repetto L; Pietropaolo M; Granata R; Ventura I; Gianni W
TI - Weekly paclitaxel infusion in elderly patients with solid tumors.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S39-40
AD - UO Oncologia INRCA, Rome.
UI - 11989922
AU - Frontini L
TI - An interesting antitumor drug in the elderly patients over the age of 70: weekly docetaxel.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S41-3
AD - Divisione di Oncologia Medica, Casa di Cura San Pio X, Milan.
UI - 11989933
AU - Puozzo C; Gridelli C; Jaworski M
TI - Pharmacokinetics of Navelbine oral in elderly patients.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S75-6
AD - Institut de Recherche Pierre Fabre, Boulogne.
UI - 11916547
AU - Laack E; Mende T; Durk H; Kneba M; Dickgreber N; Welte T; Muller T;
TI - Scholtze J; Graeven U; Jasiewicz Y; Edler L; Hossfeld DK Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial.
SO - Eur J Cancer 2002 Mar;38(5):654-60
AD - Department of Oncology and Haematology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. email@example.com
The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.
UI - 11742713
AU - Novello S; le Chevalier T
TI - ALIMTA (pemetrexed disodium, LY231514, MTA): clinical experience in non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S107-9
AD - Department of Medicine, Institut Gustave-Roussy, Villejuif, France. firstname.lastname@example.org
ALIMTA is a novel, multi-targeted antifolate which inhibits several enzymes of the folate pathways and it has demonstrated a broad spectrum of clinical activity in multiple tumor types, including colorectal, breast, non-small cell lung cancer (NSCLC), pancreatic, head and neck, bladder and cervical cancers. ALIMTA has been tested in different patient populations, including those who have received no prior chemotherapy, those who have relapsed following prior platinum-containing therapy, and those who have relapsed following prior chemotherapy without platinum. In every group was demonstrated an activity comparable to currently used new drugs. ALIMTA was also studied in association with cisplatin in chemotherapy-naive patients and the overall response rate is comparable to other current combination to add vitamin supplementation to reduce toxicity and early indications are that the frequency of serious toxicities resulting from ALIMTA treatment has been reduced. On the basis of the results of the studies reviewed, it is clear that ALIMTA is emerging as a new drug in the management of NSCLC.
UI - 11742714
AU - Momparler RL; Ayoub J
TI - Potential of 5-aza-2'-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S111-5
AD - Centre de recherche, Hopital Ste-Justine, Sherbrooke West, 3175 Cote Ste-Catherine, Montreal, Quebec, Canada. email@example.com
Although new agents and drug combinations have increased the response rate in advanced non-small cell lung cancer (NSCLC), long-term survivors are rare. There is an urgent need to develop new chemotherapeutic approaches for disease. In a previous pilot phase I-II study on 5-aza-2'-deoxycytidine (5-AZA-CdR) in patients with stage IV NSCLC, we observed several interesting responses, including one patient that was still alive (68 months) at the time of publication of our results. In the present report, we want to point out the long-term follow up of this patient, who survived 81 months, and discuss the interesting mechanism of action of 5-AZA-CdR that may have been responsible for this interesting response. 5-AZA-CdR is a potent inhibitor of DNA methylation. Recent progress in this field has shown that aberrant methylation of the promoter region of tumor suppressor genes inhibits their expression. This epigenetic event can contribute to tumorigenesis. Since 5-AZA-CdR can reactivate these genes by blocking DNA methylation, it has the potential to reverse tumorigenesis. This novel mode of action makes it an interesting agent to investigate for the chemotherapy of malignant disease, including lung cancer.
UI - 11742697
AU - Santo A; Pedersini R; Pasini F; Terzi A; Pari F; Cartei G; Sibau A;
TI - Molino A; Maiorino A; Panza N; Oletti MV; Maluta S; Calabro F; Cetto GL A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S15-20
AD - Department of Medical Oncology, University of Verona, Verona, Italy. firstname.lastname@example.org
BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.
UI - 11742698
AU - Mattson K; Abratt R; Ten GV; Krofta K; Tonelli D; Avril I
TI - Docetaxel as neo-adjuvant therapy for radically treatable stage III non-small cell lung cancer: early results of an international phase III study.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S21-3
AD - Department of Medicine, Helsinki University Central Hospital, PB 340, FIN 00029 HUS Helsinki, Finland. email@example.com
UI - 11742699
AU - Rinaldi M; Crino L
TI - Induction chemotherapy with gemcitabine and cisplatin in stage III non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S25-30
AD - Oncologia Medica B, Istituto Regina Elena, Via E. Chianesi 53, 00144 Rome, Italy. firstname.lastname@example.org
The necessity of improving the long-term survival of patients with locally advanced non-small cell lung cancer (NSCLC) points out on the one hand the limit of surgery alone and, on the other hand, the need of combined modality therapy, in which the role of chemotherapy to control distant metastases is prominent. Recent experiences support the efficacy of neoadjuvant chemotherapy with or without radiotherapy. Phase II studies show response rates of 50-80% and median survival longer than 2 years. Phase III studies suggest that neoadjuvant chemotherapy improves survival and objective responses, and induces higher percentages of complete resections compared with surgery alone or chemotherapy and radiotherapy. The gemcitabine-cisplatin regimen has proved its efficacy in NSCLC advanced disease with response rate greater than 40% in phase II and III trials. Representing one of the regimens most used in Europe, its activity has been investigated also in the neoadjuvant setting. Phase II studies have reported an average response rate greater than 60%, complete surgical resections in 60-70% of the cases, and 1-year survival of about 60%. A modern tendency is to use neoadjuvant chemotherapy in very early stages of NSCLC. Gemcitabine-cisplatin regimen has been used as a randomised clinical trial (chemotherapy for early stages trial, CHEST) to compare the efficacy of surgery alone versus surgery plus preoperative chemotherapy in early-stage disease (T2-3N0, T1-2N1, T3N1), and to evaluate the progression free survival.
UI - 11742695
AU - Galligioni E; Ferro A
TI - Angiogenesis and antiangiogenic agents in non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S3-7
AD - Department of Medical Oncology, S. Chiara Hospital, 38100 Trento, Italy. email@example.com
Tumour angiogenesis is the result of the imbalance between a large number of mediators with angiogenic and antiangiogenic activity. It may be a very early process in vivo and it may follow different pathways in different organs. Moreover, different roles of angiogenic molecules have been observed in normal and neoplastic lung and striking differences between non-small cell lung carcinomas (NSCLC) and SCLC have been observed. Contradictory results are reported in the literature on the association of angiogenesis with poor prognosis in NSCLC. Among the currently available antiangiogenic therapies, the inhibitors of vascular endothelial growth factor (VEGF), and their receptor (VEGFR) and matrix metallo-proteinase (MMP), some antivascular agents and the antiangiogenic scheduling of chemotherapy are beginning to show clinical efficacy. The best use of the antiangiogenic therapies will probably be in presence of low tumour burdens and in association with chemotherapy. However, new surrogate markers of tumour response have to be defined.
UI - 11742700
AU - Valerio MR; Russo A; Latteri MA; Modica G; Gulotta G; Armata MG; Bajardi
TI - E; Cicero G; Pantuso G; Grassi N; Agosta G; Gebbia N Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S31-5
AD - Servizio di Chemioterapia, Policlinico Universitario P.Giaccone, Via del Vespro, 127-90127, Palermo, Italy.
To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age
UI - 11742701
AU - Tumolo S; Toffoli G; Saracchini S; Lo Re G; Bruschi G; Boccieri MG
TI - Topoisomerase I inhibitors combination chemotherapy in non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S37-46
AD - U.O. Oncologia and Pneumologia, AOS-S. Maria degli Angeli, via Montereale 24, 33170 Pordenone, Italy.
In the last years, the main topoisomerase I inhibitors (TP1-I) (i.e. topotecan and irinotecan) have been used in combination chemotherapy in non-small cell lung cancer. Several drugs (also alternative to cisplatin) have been used in combination with TP1-I, but to date the higher remission rate obtained with combinations is not translated into a more prolonged survival in comparison with TP1-I given alone. On the other hand, the toxicity of TP1-I combinations is greater than those of TP1-I used alone. The superior efficacy of combinations versus TP1-I used alone remains an open question. Furthermore, the best schedule for TP1-I has not been completely elucidated. Randomised studies are few (only two phase III trials) and only controlled studies will be able to clarify the best TP1-I combination regimen.
UI - 11742702
AU - Georgoulias V; Samonis G; Papadakis E; Alexopoulos A; Tsiafaki X; Rapti
TI - A; Veslemes M; Grigoratou T; Palamidas P; Kouroussis C; Mavroudis D; Kakolyris S; Giannakakis T; Vlachonikolis J; Greek Cooperative Group for Lung Cancer Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S47-51
AD - University Hospital of Heraklion, Crete, Greece.
The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87-39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5-42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3-4 anaemia and thrombocytopenia between the two arms. However, grade 3-4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3-4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.
UI - 11742703
AU - Greco FA
TI - Paclitaxel-based combination chemotherapy in advanced non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S53-6
AD - The Sarah Cannon Cancer Center, 250 25th Av. North, Suite 412, Nashville, TN 37203, USA.
Paclitaxel has proven to be a useful drug for patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel-based combination chemotherapy, particularly with carboplatin, has become a very popular combination in the US. This article will review the conclusions of several studies regarding paclitaxel-based chemotherapy. The data provide evidence that this therapy produces good palliation and prolongation of survival for patients with NSCLC and is superior to older cisplatin-based chemotherapy. These results in patients with advanced disease have important implications for neoadjuvant and/or adjuvant approaches in patients with lower stages of disease, and several studies are ongoing.
UI - 11742704
AU - Pronzato P; Vigani A; Tognoni A; Vaira F; Canessa P
TI - Anthracyclines in non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S57-9
AD - Department of Medical Oncology, Ospedale S. Andrea, 19100 La Spezia, Italy. firstname.lastname@example.org
The literature concerning the use of anthracyclines in the treatment of non-small cell lung cancer (NSCLC) is reviewed here. Overall, the activity of doxorubicin (DOXO) is unsatisfactory, whereas, the analogous epidoxorubicin (EPI) yields a 30% response rate (RR) when administered at intermediate-high doses. All active drugs, including EPI, should be considered to design the most active combination. Mainly, in the setting, in which an objective response is very important, for instance the neo-adjuvant pre-operatory setting.
UI - 11742705
AU - Van Putten JW
TI - Activity of the combination of high-dose epirubicin with gemcitabine in advanced non-small-cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S61-4
AD - Department of Pulmonary Diseases, University Hospital, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. email@example.com
UI - 11742706
AU - Frasci G; Lorusso V; Panza N; Comella P; Nicolella G; Bianco A;
TI - DeCataldis G; Belli M; Iannelli N; Massidda B; Mascia V; Comella G; De Lena M Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase III trial.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S65-9
AD - Division of Medical Oncology, National Turnor Institute, Via M Semmola 80131, Naples, Italy. firstname.lastname@example.org
OBJECTIVE: This phase III study was aimed at evaluating whether the addition of gemcitabine (G) to vinorelbine (V) could improve the survival and quality of life (QoL) of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, aged >or=70 years, were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1200 mg/m(2) plus V 30 mg/m(2) on days 1 and 8 every 3 weeks. Survival was the main end point of the study. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned on the first 60 patients per arm. RESULTS: In May 1999, an interim analysis was performed with the survival data of the first 120 eligible patients (V(arm)=60, G+V(arm)=60). Forty-nine patients had stage IIIB disease and 71 patients stage IV disease, median potential follow-up of 14 months (range; 3-22), 93 patients had died (G+V(arm)=41, V(arm)=52). Median survival time (MST) was 29 weeks and projected 1-year survival was 30% in the G+V(arm); these values were 18 weeks and 13% in the V(arm). At multivariate Cox analysis, the risk of death in the G+V(arm) compared with V(arm) was 0.48 (95% C1=0.29-0.79; P<0.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The ORR was 22 and 15% in the G+V and V(arms), respectively. Toxicity was not irrelevant in both arms. CONCLUSIONS: G+V treatment is associated with a significantly better survival than V alone in elderly NSCLC patients. The magnitude of the difference justifies the early closure of the study. The G+V regimen is now the SICOG reference regimen in this type of patients.
UI - 11742707
AU - Kakolyris S; Kouroussis C; Souglakos J; Agelaki S; Kalbakis K; Vardakis
TI - N; Vamvakas L; Georgoulias V Cisplatin and irinotecan (CPT-11) as second-line treatment in patients with advanced non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S71-6
AD - Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, PO Box 1352, 71110 Heraklion, Crete, Greece. email@example.com
Irinotecan (CPT-11) and cisplatin (P) are both active agents against non-small cell lung cancer (NSCLC), and their combination has shown in vitro an additive or synergistic effect. We conducted a phase II study to determine the toxicity and efficacy of their combination as salvage treatment in patients with advanced NSCLC progressing after a docetaxel-based front line regimen. Forty-four patients with histologically confirmed NSCLC were enrolled. The patients' median age was 60.5 years; 39 patients (87%) were male; 38 (86%) had stage IV disease; and 32 (73%) had a performance status (WHO) 0-1. CPT-11 was administered as a 60 min i.v. infusion at a dose of 100 mg/m(2) on day 1 and 110 mg/m(2) on day 8; P was administered at a dose of 80 mg/m(2) on day 8 after CPT-11 administration. Treatment was repeated every 3 weeks. A total of 159 chemotherapy cycles was administered. In an intention-to-treat analysis, nine patients (22; 95% CI: 9.28-34.62%) achieved a partial response (PR), 8 (20%) had stable disease (SD), and 24 (58%) progressive disease (PD). The median duration of response was 4 months, the median time-to-progression (TTP) 8 months, and the median survival for the entire group 8 months. Grade 3-4 neutropenia was observed in 20 (46%) patients and in four cases this was febrile, requiring patient's hospitalisation. Grade 3-4 thrombocytopenia occurred in four (9%) patients. Grade 3-4 diarrhoea was seen in 12 (27%) patients and three of them required hospitalisation. Grade 2-3 neurotoxicity was observed in two (4%) patients and grade 2-3 fatigue in 14 (32%). Other toxicity was mild and no treatment-related death was reported. The combination of CPT-11 and P is a safe, well-tolerated, and active regimen for the treatment of patients with advanced NSCLC previously treated with a docetaxel-based front-line regimen.
UI - 11742708
AU - Agelaki S; Bania H; Kouroussis C; Blazoyiannakis G; Souglakos J;
TI - Tsiafaki X; Kalbakis K; Rapti A; Androulakis N; Georgoulias V; Papadakis E Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S77-80
AD - Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion 71110, Crete, Greece. firstname.lastname@example.org
OBJECTIVE: A phase II study was conducted to evaluate the efficacy and toxicity of vinorelbine-carboplatin (VNB-C) combination as a salvage treatment in patients with advanced non-small cell lung cancer (NSCLC) progressing after or failing previous non-platinum, taxane-based treatment. PATIENTS AND METHODS: Thirty-seven patients with cytologically or histologically confirmed NSCLC were enrolled. VNB 30 mg/m(2) was administered on days 1 and 8 and C 300 mg/m(2) on day 1 every 28 days. G-CSF (5 microg/kg per day s.c.) was used prophylactically on days 10-15 in case of grade 3-4 neutropenia or febrile neutropenia after the first cycle. RESULTS: Twenty-nine patients were evaluable for response and all were evaluable for toxicity. In an intention-to-treat analysis, two (5%) complete and four (11%) partial responses were documented for an overall response rate of 16% (95% CI, 4.49-28.84%). Eleven (30%) patients experienced disease stabilisation and 20 (54%) disease progression. The median duration of response was 7.5 months, the median TTP was 9 months, and the median survival was 8.5 months. Patients with objective remission and stable disease had a statistically significant survival benefit over patients with disease progression. Grade 3 and 4 neutropenia occurred in three (8%) and ten (27%) patients, respectively, and six cases (16%) were complicated with fever. Grade 4 thrombocytopenia was documented in one (3%) patient. Non-hematological toxicity was mild, with grade 2 and 3 asthenia reported in 18 (48%) patients. No treatment-related deaths occurred. CONCLUSION: VNB-C combination is well tolerated and retains a notable degree of activity in NSCLC patients progressing after previous non-platinum, taxane-based treatment. Moreover, it confers tumour growth control in a significant proportion of patients, and this seems to be associated with a survival benefit for them.
UI - 11742709
AU - Caffo O
TI - Radiosensitization with chemotherapeutic agents.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S81-90
AD - Department of Medical Oncology, Santa Chiara Hospital, 38100 Trento, Italy. email@example.com
The combination of low-dose chemotherapy and thoracic radiotherapy is one of the treatments proposed in an attempt to improve the prognosis of locally advanced non-small cell lung cancer. Chemotherapeutic drugs administered at subtoxic doses act by means of a radiosensitization mechanism. Platinum-derived drugs have been historically used as radiosensitizers, without cumulative unacceptable toxicity. Many new chemotherapeutic agents, which have shown promising results in terms of disease control in advanced non-small cell lung cancer, show also a radiosensitizing activity. However, the optimal dose and timing of such drugs when used concurrently to radiotherapy are unknown. This paper will review the results obtained using new chemotherapeutic drugs as radiosensitizers.
UI - 11742696
AU - Novello S; le Chevalier T
TI - Is there a standard strategy in the management of locally advanced non-small cell lung cancer?
SO - Lung Cancer 2001 Dec;34 Suppl 4():S9-14
AD - Departement of Medicine, Institut Gustave-Roussy, Villejuif, France.
Lung cancer is the leading cause of cancer mortality in the United States for both men and women. Twenty to thirty percent of patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable tumors. 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 was conventional thoracic radiotherapy for locally advanced NSCLC, but when treated with radiotherapy alone, less than 10% of patients survived for 5 years or more. Sixty to seventy percent 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 - 11742711
AU - Klastersky J; Paesmans M
TI - Response to chemotherapy, quality of life benefits and survival in advanced non-small cell lung cancer: review of literature results.
SO - Lung Cancer 2001 Dec;34 Suppl 4():S95-101
AD - Department of Medicine, Institut Jules Bordet, Rue Heger-Bordet 1, B 1000, Brussels, Belgium. firstname.lastname@example.org
The survival benefit obtained with chemotherapy administration in advanced non-small cell lung cancer (NSCLC) patients has been demonstrated by numerous meta-analyses published between 1993 and 1999 on randomised trials comparing best supportive care with or without chemotherapy. However, some clinicians are still reluctant to prescribe chemotherapy in these patients, arguing that the benefit is too small to counterbalance the side effects. The goal of this paper is to review the reasons favouring the administration of chemotherapy. First, there is a demonstrated relationship between response to chemotherapy and survival, although more data are needed to assess response to chemotherapy as a surrogate for survival. Secondly, recent randomised trials comparing best supportive care to chemotherapy, but not included in the meta-analyses, have successfully incorporated quality of life (QoL) as an endpoint, sometimes as a primary endpoint. The survival benefit shown by the meta-analyses is confirmed by these latter trials; in addition, the QoL assessments, despite some methodological problems inherent to attrition in these poor prognosis patients, also favour chemotherapy with regard to some global aspects, such as physical, functioning, emotional, cognitive or social components, as well as some lung cancer symptoms. We conclude that there are no longer convincing arguments against chemotherapy administration in patients with advanced NSCLC, at least in patients eligible for inclusion in clinical trials.
UI - 11914903
AU - Sadava D; Ahn J; Zhan M; Pang ML; Ding J; Kane SE
TI - Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.
SO - Cancer Chemother Pharmacol 2002 Apr;49(4):261-6
AD - Division of Molecular Medicine, City of Hope Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA. email@example.com
PURPOSE: We examined the pharmacology, cell biology and molecular biology of small-cell lung carcinoma cells treated with four extracts of Chinese herbal medicines. Many cancer patients take these medicines, but their effects at the cellular level are largely unknown. We were especially interested in the effects on drug-resistant cells, as resistance is a significant clinical problem in lung cancer. METHODS: Drug-sensitive (H69), multidrug-resistant (H69VP) and normal lung epithelial cells (BEAS-2) were exposed to extracts from two plants used in Chinese herbal medicine for lung cancer: Glycorrhiza glabra (GLYC) and Olenandria diffusa (OLEN), and to extracts of two commercially available combinations of Chinese herbal medicines, SPES (15 herbs) and PC-SPES (8 herbs). Cytotoxicity was measured in terms of cell growth inhibition (IC(50)). The kinetics of DNA fragmentation after exposure to the herbal extracts was measured by BudR labeling followed by ELISA. Apoptosis was measured by the TUNEL assay followed by flow cytometry. Expression of apoptosis- and cell cycle-related genes was measured by reverse transcription of mRNA followed by filter hybridization to arrays of probes and detection by chemiluminescence. RESULTS: In each case, the four herbal extracts were equally cytotoxic to H69 and H69VP and less cytotoxic to BEAS-2. All four extracts induced DNA fragment