National Cancer Institute®
Last Modified: July 1, 2002
UI - 11377599
AU - Georgoulias V; Papadakis E; Alexopoulos A; Tsiafaki X; Rapti A; Veslemes
TI - M; Palamidas P; Vlachonikolis I; Greek Oncology Cooperative Group (GOCG) for Lung Cancer Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial.
SO - Lancet 2001 May 12;357(9267):1478-84
AD - Department of Medical Oncology, University General Hospital of Heraklion, POBox 1352, Heraklion 71110, Crete, Greece. email@example.com
BACKGROUND: Docetaxel in combination with cisplatin or gemcitabine are active chemotherapy reigimes against non-small-cell lung cancer. We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial. METHODS: Patients with stage IIIB or IV lung cancer who had not had prior chemotherapy were allocated either to group 1 and treated with docetaxel (100 mg/m(2), day 1) and cisplatin (80 mg/m(2), day 2) or to group 2 and treated with gemcitabine (1100 mg/m(2), days 1 and 8) and docetaxel (100 mg/m(2), day 8). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)) had appropriate standard premedication. Response and toxicity were assessed using WHO criteria. Analysis was by intention to treat. FINDINGS: 441 patients were randomly assigned to receive docetaxel/cisplatin (group 1, n=219) or gemcitabine/docetaxel (group 2, n=222). 14 patients in group 1 and 21 patients in group 2 were not evaluable. Objective response rates were similar in the two groups: group 1, 32.4% (95% CI 26.2-38.6%; 1.4% complete response and 31% partial response); group 2, 30.2% (24.5-36.2%; 0.9% complete response and 29.3% partial response). The two groups did not differ in median duration of response, time to tumour progression, overall survival, or 1 year or 2 year survival rates. INTERPRETATION: Both drug combinations had comparable activity in patients with advanced cancer who had not previously had chemotherapy; however, gemcitabine and docetaxel had the most favourable toxicity profile.
UI - 11675089
AU - Satoh H; Sekizawa K
TI - Chemotherapy for non-small-cell lung cancer.
SO - Lancet 2001 Oct 13;358(9289):1270-1; discussion 1271-2
UI - 11880710
AU - Booton R; Thatcher N
TI - Chemotherapy in advanced nonsmall cell lung cancer: indication, intensity, and duration.
SO - Curr Opin Oncol 2002 Mar;14(2):191-8
AD - CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.
Platinum-based combination and single-agent chemotherapy have become accepted as treatments for locally advanced and metastatic nonsmall cell lung cancer as a consequence of improved survival, quality of life, and symptom control compared with best supportive care. However, it is clear that a therapeutic plateau has been reached with current combinations requiring a re-evaluation of strategies to improve clinical outcomes. Dose intensification may offer one way in which to achieve better results, as may extension of the duration of treatment. The evidence suggests that dose intensification is a useful tool, and that its use in combination with markers of treatment duration and cumulative dose may help to maximize results from current active drug combinations.
UI - 11880711
AU - Gridelli C; Maione P; Barletta E
TI - Individualized chemotherapy for elderly patients with nonsmall cell lung cancer.
SO - Curr Opin Oncol 2002 Mar;14(2):199-203
AD - Division of Medical Oncology B, National Cancer Institute, Naples, Italy. firstname.lastname@example.org
Approximately one third of all patients with nonsmall cell lung cancer (NSCLC) are over the age of seventy. Elderly patients tolerate chemotherapy poorly because of impaired organ function and comorbidities. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy. A multidimensional geriatric evaluation is important to plan appropriate treatments. At present, there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemoradiotherapy in locally advanced disease increases toxicity and seems determine no survival advantage as compared with radiation therapy alone. In advanced disease, single-agent vinorelbine proves to be active and well-tolerated, and compared with best supportive care, improves survival and perhaps quality of life. Gemcitabine is active and also well tolerated. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared with single-agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single-agent chemotherapy should remain the standard treatment. The choice of the drug should be based on the toxicity profile of each drug and type of comorbid conditions. In the near future, new therapeutic strategies and biologic agents could improve present results.
UI - 11895896
AU - Hahm HA; Ettinger DS; Bowling K; Hoker B; Chen TL; Zabelina Y; Casero RA
TI - Jr Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer.
SO - Clin Cancer Res 2002 Mar;8(3):684-90
AD - The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
PURPOSE: Polyamines are essential for tumor growth; consequently, agents that interfere with their metabolisms have been developed as antineoplastic agents. Diethylnorspermine (DENSPM) is one such agent. A focused Phase I clinical trial in patients with advanced non-small cell lung cancer was undertaken. EXPERIMENTAL DESIGN: Twenty-nine patients were treated with DENSPM using a dosing schedule of once daily for 5 days. Doses ranged from 25 mg/m(2)/day to 231 mg/m(2)/day. RESULTS: The dose-limiting toxicity was determined to be gastrointestinal including asthenia, abdominal cramps, diarrhea, and nausea. The maximal tolerated dose was 185 mg/m(2)/day for 5 days. At drug dosages for which it was possible to estimate, serum half-life ranged from 0.5 to 3.7 h without apparent dose dependence. Maximal serum concentrations increased with dosage. However, the increase was greater than the proportional increase of the administered dose. There were no objective disease responses observed during the Phase I trial. CONCLUSIONS: The results of the Phase I clinical trial suggest that DENSPM can safely be administered to patients with minimal toxicity. Furthermore, the observed dose-limiting toxicity is unique to DENSPM, thus underscoring the potential for DENSPM to be a suitable agent for chemotherapy in combination with agents possessing different spectrums of toxicities.
UI - 10931451
AU - Paesmans M; Sculier JP; Lecomte J; Thiriaux J; Libert P; Sergysels R;
TI - Bureau G; Dabouis G; Van Cutsem O; Mommen P; Ninane V; Klastersky J Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.
SO - Cancer 2000 Aug 1;89(3):523-33
AD - Institut Jules Bordet, Brussels, Belgium.
BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies. Copyright 2000 American Cancer Society.
UI - 11955650
AU - Gajra A; Tatum AH; Newman N; Gamble GP; Lichtenstein S; Rooney MT;
TI - Graziano SL The predictive value of neuroendocrine markers and p53 for response to chemotherapy and survival in patients with advanced non-small cell lung cancer.
SO - Lung Cancer 2002 May;36(2):159-65
AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
BACKGROUND: A minority of patients (30-40%) with advanced non-small cell lung cancer (NSCLC) have objective responses to chemotherapy. Therefore, defining molecular features that determine resistance or response to chemotherapy would have important implications in this disease. Several studies have suggested that patients whose tumors have neuroendocrine features may be more responsive to chemotherapy. In addition, increased expression of p53 may play a role in chemotherapy resistance in patients with NSCLC. METHODS: The objective of this study was to analyze retrospectively, the correlation between marker expression and response to chemotherapy and survival using immunohistochemistry for neuroendocrine markers and p53. Ninety patients with unresectable stage III or IV NSCLC, treated with platinum based combination chemotherapy were evaluated. The pathological specimens were obtained prior to chemotherapy. RESULTS: There was no statistically significant correlation between any individual marker and response to chemotherapy. However, patients with tumors with increased expression of p53 were more likely to have progressive disease following chemotherapy (P=0.02). Similarly, patients with tumors lacking neuroendocrine expression and with increased expression of p53 were more likely to have progressive disease when compared to patients with tumors with normal p53 expression and neuroendocrine differentiation (P=0.03). Normal expression of p53 along with the presence of neuroendocrine differentiation was a favorable factor for both survival (P=0.05) and time to disease progression (P=0.04) in the multivariate analysis. CONCLUSION: The presence of neuroendocrine markers alone was not predictive of response to chemotherapy and did not impact on the survival of this group of patients with advanced stage NSCLC. The normal expression of p53 together with neuroendocrine differentiation seems to impact favorably on overall survival time and time to disease progression without significant improvement in response to chemotherapy.
UI - 11955653
AU - Manegold C; Buchholz E; Kloeppel R; Kreisel C; Smith M
TI - Phase I dose-escalating study of raltitrexed ('Tomudex') and cisplatin in metastatic non-small cell lung cancer.
SO - Lung Cancer 2002 May;36(2):183-9
AD - Thorax-Klinik Heidelberg GmbH, Innere Medizin/Onkologie, Amalienstr. 5, Germany. email@example.com
BACKGROUND: The aim of this Phase I, dose-escalation study was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of a raltitrexed ('Tomudex') and cisplatin combination in patients with previously untreated, metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received raltitrexed (15-min intravenous infusion), followed by cisplatin (1-h intravenous infusion), every 3 weeks at escalating dose levels. Results: In total, 21 patients entered the study. No DLT was observed up to dose level 4 (raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2)), or in the first 3 patients who received dose level 5 (raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2)). However, 1 patient, entered at dose level 6 (raltitrexed 4.0 mg/m(2) plus cisplatin 80 mg/m(2)) experienced severe toxicity (including grade 3 diarrhea), and no further patients were recruited at this level. Of 4 additional patients who received raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), 3 also experienced DLTs. The most common adverse events included nausea/vomiting, asthenia, diarrhea, and hematologic toxicities. Of 19 patients evaluated for response, 3 achieved a partial response, 13 had stable disease, and 3 progressed. CONCLUSIONS: The MTD is raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), and the RD for future studies is raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2); DLTs were diarrhea and asthenia. The combination of raltitrexed and cisplatin shows clinical activity in patients with metastatic NSCLC.
UI - 11955654
AU - Thomas P; Robinet G; Ferri-Dessens RM; Lena H; Gouva S; Vernejoux JM;
TI - Kleisbauer JP Phase I trial of gemcitabine and carboplatin in metastatic non-small-cell lung cancer: a Groupe Francais de Pneumo-Cancerologie Study.
SO - Lung Cancer 2002 May;36(2):191-8
AD - Service d'Oncologie Respiratoire, Hopital Sainte-Marguerite, 270 Bd Sainte-Marguerite, 13 009 Marseille, France. firstname.lastname@example.org
BACKGROUND: The purpose of this study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicity (DLT) of the 21 days carboplatin plus gemcitabine regimen in previously untreated patients with stage IV non small-cell lung cancer (NSCLC). METHODS: At least three patients were entered at each dose level. The starting dose was carboplatin AUC 4 mg/ml per min (Area Under the Curve; Calvert formula) on day 1 and gemcitabine 750 mg/m(2) on days 1 and 8. Carboplatin was increased to AUC 5 (level 3, 4) then to AUC 6 (level 5-7). Gemcitabine was increased to 875 (level 2, 3), 1000 (level 4, 5), 1250 (level 6) and finally 1500 mg/m(2) (level 7). Twenty-nine patients were entered into this phase I study. RESULTS: At dose level 6, a DLT (grade 4 thrombocytopenia) was observed in one out of six patients. At dose level 7, no DLT was observed during the first course, so the MTD was not reached. During the second course, two out of four patients presented grade 4 thrombocytopenia. None of the five patients receiving two courses at level 6 presented a DLT, so this level was retained for further phase II studies. Of the 25 patients assessable for response, five achieved partial responses with a response rate of 20% (95% CI, 7 to 41%). The median survival time was 7 months and the 1-year survival rate was 24% (95% CI, 9 to 45%). CONCLUSION: The combination of carboplatin given on day 1 and gemcitabine given on days 1 and 8 every 3 weeks seems to be an acceptable regimen. The DLT consists exclusively of severe thrombocytopenia. Despite the MTD was not reached with carboplatin AUC 6 mg/ml per min and gemcitabine 1500 mg/m(2), the recommended dose for further phase II studies is carboplatin AUC 6 mg/ml per min and gemcitabine 1250 mg/m(2).
UI - 12088266
AU - Frassineti GL; Ibrahim T; Zoli W; Monti M; Ricotti L; Nanni O; Amadori D
TI - Docetaxel followed by gemcitabine in the treatment of advanced non-small cell lung cancer: a phase I study.
SO - Tumori 2002 Mar-Apr;88(2):99-103
AD - Department of Medical Oncology, Pierantoni Hospital, Forli, Italy.
AIMS AND BACKGROUND: Based on the results of a preclinical study, a phase I trial was conducted to evaluate the feasibility of administering docetaxel followed by gemcitabine in non-small cell lung cancer patients. STUDY DESIGN: Sixteen patients with advanced non-small cell lung cancer (stages III B-IV) were treated on the 1st day with docetaxel and on the 8th day with gemcitabine. Treatment was repeated every three weeks for a maximum of six cycles. Five groups received docetaxel/gemcitabine (mg/ml): 50/800, 60/800, 60/900, 60/1,000, 70/1,000. All patients and 57 cycles were assessed for toxicity. RESULTS: The most important side effects were grade IV neutropenia in 4 patients (2 at the 60/1000 level and 2 at the 70/1000 level) and grade III leukopenia and neutropenia without fever in 4 and 6 patients, respectively. Maximum tolerated dose was not reached. CONCLUSIONS: The sequence docetaxel-gemcitabine appears well tolerated and easy to administer. For this reason, a phase II study is ongoing to fully assess its antitumor activity.
UI - 12042986
AU - Baldini E; Ardizzoni A; Prochilo T; Cafferata MA; Boni L; Tibaldi C
TI - Gemcitabine, ifosfamide and Navelbine (GIN): a platinum-free combination in advanced non-small-cell lung cancer (NSCLC).
SO - Cancer Chemother Pharmacol 2002 May;49 Suppl 1():S25-8
AD - U.O. Oncologia Medica Ospedale S. Chiara, via Roma n.67, 56100 Pisa, Italy. email@example.com
PURPOSE: To evaluate the activity and toxicity of gemcitabine, ifosfamide and Navelbine (GIN) in advanced NSCLC. PATIENTS AND METHODS: Stage IIIB/IV NSCLC, WHO performance status <2 and bidimensionally measurable disease were required to enter the study. Gemcitabine 1000 mg/m(2) day 1 and 1000 or 800 mg/m(2) day 4, ifosfamide 3 g/m(2) day 1 (with mesna), Navelbine 25 mg/m(2) day 1 and 25-20 mg/m(2) day 4 were administered on an outpatient basis every 3 weeks for a maximum of six courses. Objective remissions (ORs) were evaluated every two courses. According to Simon's optimal two-stage design, more than 18 ORs out of 54 patients were required to establish the activity of this regimen. RESULTS: The study group comprised 50 patients. Most patients had metastatic disease (79%) and nonsquamous histology (71%). The total number of courses administered was 200, with a median per patient of 4 (range 1-6). Myelosuppression, in particular leukopenia, was the most frequent toxicity: grade 3-4 neutropenia (WHO) occurred in 47% of the courses, while grade 3-4 thrombocytopenia and anemia affected, respectively, 6.6% and 3.5% of the courses only. Twelve episodes of febrile neutropenia were recorded, and three patients required hospital admission. No toxic deaths were reported. Nonhematological toxicity was generally mild and not clinically relevant. A total of 25 ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI 37.4-66.5%). One-year survival was 46.5%. CONCLUSIONS: The GIN combination showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose limiting. This non-platinum-based triplet may be a valuable alternative to standard platinum-containing regimens and it is under evaluation in an ongoing randomized trial.
UI - 11824893
AU - Gregory RK; Smith IE; Norton A; Ashley S; O'Brien ME
TI - Mitomycin C, vinblastine and carboplatin: effective outpatient chemotherapy for advanced non-small cell carcinoma of the lung (NSCLC).
SO - Clin Oncol (R Coll Radiol) 2001;13(6):483-7
AD - Royal Marsden Hospital, Sutton, UK.
The majority of patients diagnosed with non-small cell lung carcinoma (NSCLC) present with advanced disease and, as such, are treated with palliative intent. Platinum-based combination chemotherapy plays an important role in the management of these patients, with response rates to most regimens being in the range of 30%-40%. with symptom relief in up to 60%. One of the most commonly utilized combinations is mitomycin C, vinblastine and cisplatin (MVP). Owing to the hydration regimen, and to the age and performance status of many of these patients, in reality this combination often necessitates an overnight stay in hospital. A combination of drugs that could be administered as an outpatient would be beneficial to patients and could result in substantial economic benefits. Forty-three patients with Stage IlIb and IV NSCLC were treated with the MVCarbo regimen, in which the cisplatin in the MVP regimen was replaced with carboplatin. All treatment was administered on an outpatient basis. The overall objective response rate was 30%; the symptomatic response rate was 60%, which was exactly equivalent to the response rate seen in a comparable group of patients treated with MVP in a trial on duration of chemotherapy at the Royal Marsden Hospital. There was no difference in progression-free or overall survival between patients treated with the two regimens. The MVCarbo regimen resulted in response rates and survival rates equivalent to those seen with standard MVP and, as such, provides an acceptable outpatient alternative to this treatment.
UI - 12089222
AU - Hainsworth JD; Gray JR; Morrissey LH; Kalman LA; Hon JK; Greco FA
TI - Long-term follow-up of patients treated with paclitaxel/carboplatin-based chemotherapy for advanced non-small-cell lung cancer: sequential phase II trials of the Minnie Pearl Cancer Research Network.
SO - J Clin Oncol 2002 Jul 1;20(13):2937-42
AD - Sarah Cannon Cancer Center and Tennessee Oncology, PLLC, Nashville, TN 37203, USA.
PURPOSE: To provide long-term follow-up on the survival of patients with advanced non-small-cell lung cancer treated with paclitaxel/carboplatin-based regimens in a multicenter, community-based patients with newly diagnosed stage IIIB or IV non-small-cell lung cancer were treated on sequential phase II trials with the following combination regimens: paclitaxel/carboplatin, paclitaxel/carboplatin/gemcitabine, and paclitaxel/carboplatin/vinorelbine. Details of these three regimens and patient populations have been previously reported. Responding and stable patients continued treatment until tumor progression or for a recommended six treatment courses. RESULTS: After a median follow-up of 58 months (minimum follow-up, 40 months), the median survival for the entire group of patients was 8.6 months, with actual 1-, 2-, and 3-year survival rates of 40%, 19%, and 7%, respectively. The actuarial 4-year survival rate for the entire group was 4%. No statistically significant differences in survival were seen among the three regimens. Administration of all three regimens was feasible in a community-based setting; however, myelosuppression and hospitalizations for treatment of neutropenia/fever were more frequent with the three-drug regimens. CONCLUSION: Paclitaxel/carboplatin-based regimens, in addition to prolonging median survival and improving 1-year survival, result in substantial improvements in the 2-year survival of patients with advanced non-small-cell lung cancer when compared retrospectively with supportive care or traditional cisplatin-based regimens. In these sequential phase II trials, we did not demonstrate any advantages of three-drug regimens when compared with paclitaxel/carboplatin. Because few patients remain alive after 4 years with any of these chemotherapy regimens, future treatment improvements will require the introduction of novel agents.
UI - 11822756
AU - Huisman C; Postmus PE; Giaccone G; Smit EF
TI - A phase I study of sequential intravenous topotecan and etoposide in lung cancer patients.
SO - Ann Oncol 2001 Nov;12(11):1567-73
AD - Department of Pulmonary, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
PURPOSE: The topoisomerase I inhibitor topotecan (T) and the topoisomerase II inhibitor etoposide (E) are active drugs in lung cancer. The complementary functions of their targets may suggest benefit from the combined use of these agents but drug scheduling has been shown to play a critical role in preclinical models. To establish the optimal schedule and assess the impact of sequential administration of the combination of T and E, we conducted a dose finding study of sequential intravenous T and E in a four-weekly-schedule in relapsed lung cancer patients. PATIENTS AND METHODS: The importance of drug sequence was assessed in consecutive patients throughout all dose levels; patients received in the first course either T followed by E (the TE group: T on days 1-3 and E on days 4-6) or E before T (the ET group: F on days 1-3 and Ton days 4-6). The sequence of Tand E was alternated in the successive courses. In this crossover design, each patient served as his own control for analysis of hematological toxicity in which TE sequence was compared to that of the ET sequence. Moreover, hematological toxicity after the first course was compared between the TE and the ET groups. The starting dose was T/E 0.75/75 mg/m2 at dose level 1and dose escalation was planned to T/E 1.00/75 mg/nm2 at dose level 2, T/E 1.00/100 mg/m2 at dose level 3, T/E 1.25/100 mg/m2 at dose level 4 and T/E 1.50/100 mg/m2 at dose level 5. Nineteen patients (small-cell lung cancer 7, non-small-cell lung cancer 11, mesothelioma 1 patient) were included. RESULTS: The principal toxicity was myelosuppression, primarily neutropenia and thrombocytopenia. At dose level 3 several grade 4 toxicities were observed. DLT (febrile neutropenia) occurred in two patients, one in the TE and one in the ET group and precluded further dose escalation. There was no significant difference in WBC and platelet nadirs during the first course between the TE and the ET group. The influence of the sequence of administration of topotecan and etoposide was calculated by comparing the nadir values of cycles I and II for each patient. For none of the dose levels, a significant sequence-dependent effect could be detected. The MTD was reached at the doses of 100 mg/m2 topotecan and 75 mg/m2 etoposide. No objective responses were seen. CONCLUSION: Although the combined use of topoisomerase I and II inhibitors is attractive on theoretical grounds, excessive myelosuppression prevents substantial dose escalation.
UI - 11829085
AU - Osterlind K
TI - Chemotherapy in small cell lung cancer.
SO - Eur Respir J 2001 Dec;18(6):1026-43
AD - Dept of Oncology, Herlev University Hospital, Denmark.
Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC. Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy. New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3-4 series of chemotherapy and radiation delivered in 5-10 fractions. A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.
UI - 12057138
AU - Cohen EE; Vokes EE
TI - Locally advanced non-small cell lung cancer.
SO - Curr Treat Options Oncol 2001 Feb;2(1):27-42
AD - Section of Hematology and Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Locally advanced non-small cell lung cancer remains a paradoxical entity to manage. Although this type of cancer is confined to the thorax and is ostensibly curable, most patients presenting at this stage of disease eventually succumb to it. The accepted therapy presently includes chemotherapy and radiation. The exact agents, schedules, and combinations need to be defined further, although cisplatin has become the widely viewed standard cytotoxic drug in this setting. Notwithstanding, newer chemotherapeutic and biologic agents are being extensively tested to find less toxic options with greater efficacy. Drugs that are gaining widespread approval include carboplatin, paclitaxel, gemcitabine, and vinorelbine. At the same time, advances in radiation therapy are triggering a revolution in dose intensity and scheduling that will one day offer superlative local control.
UI - 12057139
AU - Wright CD; Mathisen DJ
TI - Superior sulcus tumors.
SO - Curr Treat Options Oncol 2001 Feb;2(1):43-9
AD - General Thoracic Surgical Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Superior sulcus tumors (also known as Pancoast's tumors) are an unusual presentation of non-small cell lung cancer (NSCLC) that are often initially misdiagnosed. Accurate and thorough staging is necessary prior to treatment and typically includes magnetic resonance imaging if a surgical approach is being considered. Standard therapy has been induction radiation therapy followed by resection, which results in a 5-year survival of about 30%. Complete resection remains the key to long-term survival in localized NSCLC but is difficult to achieve with superior sulcus tumors due to early invasion of bone and to vascular and nervous structures at the apex of the chest. Complete resection has been enhanced by using an anterior trans-cervicomediastinal approach that facilitates resection of anterior-based tumors that invade the subclavian vessels. Recently, induction chemoradiotherapy has been reported to enhance complete resection rates and improve survival compared with historical controls and is likely to become the new standard treatment for localized superior sulcus tumors.
UI - 12057140
AU - Edelman MJ; Khanwani SL
TI - Advanced non-small cell lung cancer.
SO - Curr Treat Options Oncol 2001 Feb;2(1):51-62
AD - University of Maryland Greenebaum Cancer Center, 22 S. Greene Street, Baltimore, MD 21201-1595, USA.
The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient's performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administration, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.
UI - 12057141
AU - Murray N; Sheehan F
TI - Limited stage small cell lung cancer.
SO - Curr Treat Options Oncol 2001 Feb;2(1):63-70
AD - British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6.
The management of limited stage small cell lung cancer begins with a firm pathologic diagnosis and careful staging. Patients with adequate pulmonary function, ambulatory performance status, and no evidence of metastatic disease outside a "tolerable" local radiotherapy volume should have consultation from both medical and radiation oncology disciplines for planning of integrated therapy. The chemotherapy prescription recommended is cisplatin plus etoposide at standard doses for four chemotherapy cycles. Thoracic irradiation should be administered concurrently with the first or second cycle of cisplatin and etoposide. Patients with complete response and excellent partial response should receive prophylactic cranial irradiation after completion of all chemotherapy.
UI - 12057142
AU - Niell HB
TI - Extensive stage small cell lung cancer.
SO - Curr Treat Options Oncol 2001 Feb;2(1):71-6
AD - Van Vleet Cancer Center, University of Tennessee-Memphis, 3N Dunlap, Memphis, TN 38163, USA.
Small cell lung cancer is a rapidly proliferating, biologically aggressive form of lung cancer that has a short survival without treatment. Chemotherapy is the foundation of the therapeutic approach to patients with small cell lung cancer. Most patients present with extensive disease, and, although few patients are cured, significant improvement in survival is possible with modern chemotherapy. The role of radiation therapy in extensive disease is palliative, and surgery has little role in patient management. The standard chemotherapy regimen for patients with small cell lung cancer has become either cisplatin or carboplatin with etoposide. Second-line chemotherapy regimens are moderately effective in patients previously responding to initial chemotherapy. Newer chemotherapy agents show promise, but few randomized trials have been completed in extensive disease. Physicians should be encouraged to include their patients with extensive small cell lung cancer in the evolving clinical trials.
UI - 12057087
AU - Lara PN Jr; Lau DH; Gandara DR
TI - Non-small-cell lung cancer progression after first-line chemotherapy.
SO - Curr Treat Options Oncol 2002 Feb;3(1):53-8
AD - Division of Hematology-Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Sacramento, CA 95817, USA. firstname.lastname@example.org
Platinum-based chemotherapy is the cornerstone of care for patients with metastatic non-small-cell lung cancer (NSCLC). It provides symptom relief, improved quality of life, and prolongation of life, compared with supportive care alone. However, all patients with stage IV disease inevitably develop resistance to chemotherapy and progressive disease. Many of these patients continue to have acceptable performance status and would therefore be eligible for second-line or even third-line treatments. Unfortunately, despite an increasing number of chemotherapeutic agents (which are effective in chemo-naive NSCLC), very few have been shown to have reproducible activity in the second-line setting. Nevertheless, recent randomized clinical trials have demonstrated that single-agent docetaxel improves survival and quality of life when delivered as second-line therapy, resulting in FDA-approval for this indication. Phase II studies evaluating other new agents, delivered singly or in combination, also have reported that gemcitabine, weekly paclitaxel, and the epidermal growth factor receptor (EGFR) inhibitors are active in a subset of patients who progress after first-line platinum-based therapy. Clinical trials are imperative in identifying additional new agents and approaches that may improve outcomes in this disease. In view of the recently established role of docetaxel, ongoing randomized studies are using a common design of single-agent docetaxel versus docetaxel plus a novel investigational agent.
UI - 11963726
AU - Schalhorn A
TI - [Modern chemotherapy in bronchial carcinoma]
SO - Internist (Berl) 2002 Mar;43(3):416-30
AD - Medizinische Klinik III, Ludwig-Maximilians-Universitat, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munchen.
UI - 12065869
AU - Ueno H; Okada S; Okusaka T; Ikeda M; Kuriyama H
TI - Phase II study of uracil-tegafur in patients with metastatic pancreatic cancer.
SO - Oncology 2002;62(3):223-7
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. email@example.com
OBJECTIVE: Uracil-tegafur (UFT) has been reported to have a broad anti-tumor activity in a variety of malignancies including colorectal cancer and breast cancer. However, its activity in pancreatic cancer has not been fully evaluated. The aim of the present study was to evaluate the anti-tumor activity and toxicity of UFT in patients with metastatic pancreatic cancer. METHODS: All patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. A dose of 360 mg/m2/day of UFT was administered orally until the appearance of disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were entered into this study. Of 21 patients evaluable for response, no patient achieved an objective tumor response; one showed no change, and the remaining 20 showed progressive disease. The median survival time for all patients was 4.2 (range: 0.9-9.0) months. The most common toxicities were nausea/vomiting and anorexia. Five patients (23%) had to discontinue UFT treatment because of gastrointestinal toxicity. CONCLUSION: This schedule of UFT did not demonstrate a significant anti-tumor activity against metastatic pancreatic cancer. Copyright 2002 S. Karger AG, Basel
UI - 12065068
AU - Clegg A; Scott DA; Sidhu M; Hewitson P; Waugh N
TI - A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer.
SO - Health Technol Assess 2001;5(32):1-195
AD - Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, University of Southampton, UK.
BACKGROUND: The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion. OBJECTIVES: This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed. METHODS: This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of l