• 1371P Diagnostic and therapeutic strategies for elderly patients with advanced non-small cell lung cancer (NSCLC): results from an EORTC pan-European survey.

      Giaj-Levra, M; Menis, J; Luciani, A; De Maio, E; Hasan, B; Berghmans, T; Massiani, M; De Waele, M; Dingemans, A; Donckele, J; et al. (2017-09)
    • Choice of second-line systemic therapy in stage IV small cell lung cancer (SCLC) - A decision-making analysis amongst European lung cancer experts

      Fruh, M; Panje, CM; Reck, M; Blackhall, Fiona H; Califano, Raffaele; Cappuzzo, F; Besse, B; Novello, S; Garrido, P; Felip, E; et al. (2020)
      Objectives: Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. Material and methods: The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. Results: The two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment. With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3-6 months since the end of first-line therapy. Conclusion: Real world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient's preference, convenience or costs have to be factored in. Keywords: Decision making; Objective consensus; Second-line chemotherapy; Small cell lung cancer (SCLC).
    • Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.

      Faivre-Finn, Corinne; Snee, M; Ashcroft, Linda; Appel, W; Barlesi, F; Bhatnagar, A; Bezjak, A; Cardenal, F; Fournel, P; Harden, S; et al. (2017-06-19)
      Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.
    • Definition of synchronous oligo-metastatic non-small cell lung cancer - a consensus report

      Dingemans, A; Hendriks, LEL; Berghmans, T; Levy, A; Hasan, B; Faivre-Finn, Corinne; Giaj-Levra, M; Giaj-Levra, N; Girard, N; Greillier, L; et al. (2019)
      A 70-year-old man reported progressive weight loss, fatigue and a generalised rash. The rash was consistent with necrolytic migratory erythema, further investigations were performed and the patient was diagnosed with a mass in the tail of the pancreas, in keeping with a localised glucagonoma. Somatostatin analogue therapy was started for symptom control, leading to complete resolution of the skin rash and an improvement in constitutional symptoms. Subsequently, the pancreatic lesion was excised, and pathology assessment confirmed the diagnosis of well-differentiated neuroendocrine tumour with high expression of glucagon compatible with glucagonoma.
    • Durvalumab impact in the treatment strategy of stage III non-small cell lung cancer (NSCLC): an EORTC Young Investigator Lung Cancer Group Survey

      Levra, MG; Benet, J; Hasan, B; Berghmans, T; Bruni, A; Dingemans, A; Levra, NG; Edwards, J; Faivre-Finn, Corinne; Girard, N; et al. (2019)
    • EORTC Lung Cancer Group survey on the definition of NSCLC synchronous oligometastatic disease

      Levy, A; Hendriks, LEL; Berghmans, T; Faivre-Finn, Corinne; Giaj-Levra, M; Giaj-Levra, N; Hasan, B; Pochesci, A; Girard, N; Greillier, L; et al. (2019)
      BACKGROUND: Synchronous oligometastatic disease (sOM) has been described as a distinct disease entity; however, there is no consensus on OM definition (OM-d) in non-small-cell lung cancer (NSCLC). A consensus group was formed aiming to agree on a common OM-d that could be used in future clinical trials. A European survey was circulated to generate questions and input for the consensus group meeting. METHODS: A European Organisation for Research and Treatment of Cancer Lung Cancer Group (LCG)/sOM-d consensus group survey was distributed to LCG, sOM-d consensus group, and several European thoracic oncology societies' members. RESULTS: 444 responses were analysed (radiation oncologist: 55% [n = 242], pulmonologist: 15% [n = 66], medical oncologist: 14% [n = 64]). 361 physicians (81%) aimed to cure sOM NSCLC patients and 82% (n = 362) included the possibility of radical intent treatment in their sOM-d. The maximum number of metastases considered in sOM-d varied: 12% replied 1 metastasis, 42% ? 3, and 17% ? 5 metastases. 79% (n = 353) stated that number of organs involved was important for sOM-d, and most (80%, n = 355) considered that only ?3 involved organs (excluding primary) should be included. 317 (72%) included mediastinal lymph node involvement in the sOM-d and 22% (n = 70/317) counted mediastinal lymph node as a metastatic site. Most physicians completed sOM staging with brain magnetic resonance imaging (91%, n = 403) and positron emission tomography/computed tomography (98%, n = 437). Pathology proof of metastatic disease was a requirement to define sOM for 315 (71%) physicians. The preferred primary outcome for sOM clinical trials was overall survival (73%, n = 325). CONCLUSION: Although consensual answers were obtained, several issues remain unresolved and will require further research to agree on a sOM-d.
    • Erratum to 'Consolidative thoracic radiotherapy in stage IV small cell lung cancer: Selection of patients amongst European IASLC and ESTRO experts' [Radiother. Oncol. 135 (2019) 74-77]

      Putora, PM; Glatzer, M; De Ruysscher, D; Faivre-Finn, Corinne; Belderbos, J; Besse, B; Blackhall, Fiona H; Califano, Raffaele; Cappuzzo, F; de Marinis, F; et al. (2019)
    • Maintenance pazopanib versus placebo in non-small cell lung cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group, EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064).

      O'Brien, M; Gaafar, R; Hasan, B; Menis, J; Cufer, T; Popat, S; Woll, P; Surmont, V; Georgoulias, V; Montes, A; et al. (2015-08)
      Switch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC.
    • Management of elderly patients with NSCLC; updated expert's opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology.

      Pallis, A; Gridelli, C; Wedding, U; Faivre-Finn, Corinne; Veronesi, G; Jaklitsch, M; Luciani, A; O'Brien, M; Medical Department, European Organization for Research and Treatment of Cancer, Brussels, Belgium (2014-07)
      Non-small-cell lung cancer (NSCLC) is a very common disease in the elderly population and its incidence in this particular population is expected to increase further, because of the ageing of the Western population. Despite this, limited data are available for the treatment of these patients and, therefore, the development of evidence-based treatment recommendations is challenging. In 2010, European Organization for Research and Treatment of Cancer (EORTC) took an initiative in collaboration with International Society of Geriatric Oncology (SIOG) and created an experts panel that provided an experts' opinion consensus paper for the management of elderly NSCLC patients. Since this publication, important new data are available and EORTC and SIOG recommended to update the 2010 recommendations. Besides recommendations for surgery, adjuvant chemotherapy and radiotherapy, treatment of locally advanced and metastatic disease, recommendations were expanded, to include data on patient preferences and geriatric assessment.
    • Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial.

      Spathis, A; Fife, K; Blackhall, Fiona H; Dutton, S; Bahadori, R; Wharton, R; O'Brien, M; Stone, P; Benepal, T; Bates, N; et al. (2014-04-28)
      Fatigue is a distressing symptom occurring in more than 60% of patients with cancer. The CNS stimulants modafinil and methylphenidate are recommended for the treatment of cancer-related fatigue, despite a limited evidence base. We aimed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer (NSCLC).
    • Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2).

      Chua, S; Smith, I E; Ahern, Roger; Coombes, G A; Hickish, T; Robinson, A C; Laing, R W; O'Brien, M; Ebbs, S R; Hong, A; et al. (2005-09)
      BACKGROUND: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. PATIENTS AND METHODS: Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. RESULTS: A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. CONCLUSIONS: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.
    • A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.

      Smith, I; Ahern, Roger; Coombes, G; Howell, Anthony; Ebbs, S; Hickish, T; O'Brien, M; Mansi, J; Wilson, C; Robinson, A; et al. (2004-05)
      BACKGROUND: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer. PATIENTS AND METHODS: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate. RESULTS: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC. CONCLUSIONS: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.
    • A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer.

      Mackay, H J; O'Brien, M; Hill, S; Lees, S M; Thatcher, Nick; Smith, I E; Dunlop, D; CRC Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Glasgow, UK. hjmk1z@udcf.gla.ac.uk (2003-06)
      AIM: The aim of this study was to evaluate the activity of the combination of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer (SCLC). Patients with good prognosis disease were included who were not medically fit to tolerate conventional chemotherapy. Activity was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Fifty-eight patients, 37 men and 21 women, with histologically or cytologically confirmed SCLC, who had bi-dimensionally measurable disease, with ECOG performance status > or = 2, with adequate haematological, hepatic and renal function received first-line chemotherapy with carboplatin (AUC x 5) day 1 and vinorelbine (30 mg/m2) days 1 and 8 of a 28-day cycle. Response was assessed after every two cycles of chemotherapy, with patients receiving a maximum of six cycles of treatment. RESULTS: The combination of carboplatin and vinorelbine is an active regimen in the treatment of SCLC, with an overall intention-to-treat response rate of 55% [95% confidence interval (CI): 42-68%] with six (10%) of patients having a complete response. Median time to progression was 18 weeks (95% CI: 15-21 weeks). Median overall survival was 26 weeks (95% CI: 21-31 weeks). Ten patients failed to complete two cycles of treatment, and were not evaluable for response for the following reasons: septic death (1 neutropaenic, 1 no myelotoxicity), non-toxic death (1 tumour eroded through the pulmonary artery, 1 ischaemic heart disease) ischaemic heart disease (1) and patient decision (5). There were a total of three toxic deaths all sepsis-complicating neutropaenia. Forty-four (76%) patients experienced grade 3 or 4 neutropaenia, six (11%) grade 3 or 4 thrombocytopaenia, 10 (13%) grade 3 lethargy, three (5%) grade 3 nausea and two (3%) grade 3 diarrhoea. CONCLUSIONS: The combination of carboplatin and vinorelbine is active against SCLC but the toxicity profile in this group of patients suggests that further evaluation is not appropriate.
    • Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.

      Eisen, Tim; Thatcher, Nick; Leyvraz, Serge; Miller, Wilson H; Couture, Felix; Lorigan, Paul C; Lüthi, François; Small, David; Tanovic, Adnan; O'Brien, M; et al. (2009-04)
      OBJECTIVE: To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. RESULTS: Twenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase. CONCLUSION: This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.
    • Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer.

      O'Brien, M; Ciuleanu, Tudor; Tsekov, Hristo; Shparyk, Yaroslav; Cuceviá, Branka; Juhasz, Gabor; Thatcher, Nick; Ross, Graham A; Dane, Graham C; Crofts, Theresa; et al. (2006-12-01)
      PURPOSE: For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented. PATIENTS AND METHODS: This study randomly assigned patients with relapsed SCLC not considered as candidates for standard intravenous therapy to best supportive care (BSC) alone (n = 70) or oral topotecan (2.3 mg/m2/d, days 1 through 5, every 21 days) plus BSC (topotecan; n = 71). RESULTS: In the intent-to-treat population, survival (primary end point) was prolonged in the topotecan group (log-rank P = .0104). Median survival with BSC was 13.9 weeks (95% CI, 11.1 to 18.6) and with topotecan, 25.9 weeks (95% CI, 18.3 to 31.6). Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval (< or = 60 days). Response to topotecan was 7% partial and 44% stable disease. Patients on topotecan had slower quality of life deterioration and greater symptom control. Principal toxicities with topotecan were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing topotecan with BSC, infection grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9%, and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the topotecan arm. All cause mortality within 30 days of random assignment was 13% on BSC and 7% on topotecan. CONCLUSION: Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC.
    • A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).

      Booton, Richard; Lorigan, Paul C; Anderson, Heather; Baka, Sofia; Ashcroft, Linda; Nicolson, Marianne; O'Brien, M; Dunlop, D; O'Byrne, Kenneth J; Laurence, V; et al. (2006-07)
      BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.
    • Prophylactic cranial irradiation in stage IV small cell lung cancer: selection of patients amongst European IASLC and ESTRO experts

      Putora, P; Glatzer, M; Belderbos, J; Besse, B; Blackhall, Fiona H; Califano, Raffaele; Cappuzzo, F; de Marinis, F; Dziadziuszko, R; Felip, E; et al. (2019)
      BACKGROUND: Due to conflicting results between major trials the role of prophylactic cranial irradiation (PCI) in stage IV small cell lung cancer (SCLC) is controversial. METHODS: We obtained a list of 13 European experts from both the European Society for Therapeutic Radiation Oncology (ESTRO) and the International Association for the Study of Lung Cancer (IASLC). The strategies in decision making for PCI in stage IV SCLC were collected. Decision trees were created representing these strategies. Analysis of consensus was performed with the objective consensus methodology. RESULTS: The factors associated with the recommendation for the use of PCI included the fitness of the patient, young age and good response to chemotherapy. PCI was recommended by the majority of experts for non-elderly fit patients who had at least a partial response (PR) to chemotherapy (for complete remission (CR) 85% of radiation oncologists and 69% of medical oncologists, for PR: 85% of radiation oncologists and 54% of medical oncologists). For patients with stable disease after chemotherapy, PCI was recommended by 6 out of 13 (46%) radiation oncologists and only 3 out of 13 medical oncologists (23%). For elderly fit patients with CR, a majority recommended PCI (62%) and no consensus was reached for patients with PR. CONCLUSION: European radiation and medical oncologists specializing in lung cancer recommend PCI in selected patients and restrict its use primarily to fit, non-elderly patients who responded to chemotherapy.
    • Radical treatment of non-small cell lung cancer during the last 5 years.

      McCloskey, Paula; Balduyck, B; Van Schil, P; Faivre-Finn, Corinne; O'Brien, M; Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom. (2013-01-23)
      The management of non-small cell lung cancer (NSCLC) has continued to improve over the last 5years due to advances in surgery, radiological staging, combined modality therapies and advances in radiation technology. We have an updated staging classification (7th Edition American Joint Committee on Cancer staging) and now in 2011, a new histology classification introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications as the role of limited resection is reconsidered for early stage lesions. Surgery is curative in early stage disease. The role of surgery in locally advanced NSCLC remains controversial. The principal aim is a complete resection as this will determine long-term prognosis. Intraoperative staging of lung cancer is extremely important to determine the extent of resection according to the tumour and nodal status. Systematic nodal dissection is generally advocated to obtain accurate intraoperative staging and to help decide on adjuvant therapy. Radiotherapy currently plays a major role in the management of lung cancer as most patients are not surgical candidates due to disease stage, fitness and co-morbidities. In the last 5years we have seen continuing optimisation of chemo-radiotherapy combinations and technological advances including the development of image guided radiotherapy (IGRT), stereotactic ablative body radiotherapy (SABR) and intensity modulated radiotherapy (IMRT). Quality of life evaluation is becoming increasingly important and should be considered when deciding on a specific treatment, especially in a multimodality setting.
    • Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer.

      Von Pawel, J; Jotte, R; Spigel, D; O'Brien, M; Socinski, M; Mezger, J; Steins, M; Bosquée, L; Bubis, J; Nackaerts, K; et al. (2014-11-10)
      Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC.
    • Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer.

      Lorigan, Paul C; Woll, Penella J; O'Brien, M; Ashcroft, Linda; Sampson, Mark R; Thatcher, Nick; Weston Park Hospital, Sheffield, UK. paul.lorigan@manchester.ac.uk (2005-05-04)
      BACKGROUND: Recent dose-intensity studies of small-cell lung cancer (SCLC) have yielded conflicting results. We carried out a phase III randomized trial in patients with better-prognosis SCLC (i.e., prognostic score of 0-1) to investigate whether doubling the dose density of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with filgrastim and blood-progenitor-cell support improves survival, compared with standard ICE chemotherapy. METHODS: We studied 318 patients with pathologically proven SCLC who were randomly assigned to receive six cycles of ICE chemotherapy with a 4-week (standard arm) or 2-week (dose-dense arm) interval between cycles. Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6, which was returned 24 hours after treatment. Toxicities, including hematologic toxicity and incidence of neutropenic sepsis, were monitored. Survival was calculated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: The delivered median dose intensity was 99% (interquartile range = 96%-100%) for the standard arm and 182% (interquartile range = 163%-196%) for the dose-dense arm. After a median follow-up of 14 months, overall response to treatment was observed in 118 (80%) of the 148 evaluable patients in the standard arm and in 129 (88%) of the 147 evaluable patients in the dose-dense arm, a statistically non-significant difference. Median overall survival was 13.9 months (95% confidence interval [CI] = 12.9 to 15.8 months) in the standard arm and 14.4 months (95% CI = 12.7 to 16.0) in the dose-dense arm, and the 2-year survival was 22% (95% CI = 16% to 29%) and 19% (95% CI = 14% to 27%), respectively--neither difference being statistically significant. The median treatment free time was 286 days (95% CI = 229 to 343 days) for the standard arm and 367 days (95% CI = 321 to 413 days) for the dose-dense arm (difference = 81 days; P = .109). Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the standard arm, but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the standard arm than in the dose-dense arm (15.3% versus 11.6%, respectively; difference = 3.7%, 95% CI = -4.1% to 11.5%; P = .03). CONCLUSIONS: Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did standard ICE but did not improve overall survival.