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