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S. White



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    MO13 - SCLC I (ID 118)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO13.02 - Age as a prognostic factor in small cell lung cancer. A pooled analysis of randomized clinical trials from the Manchester lung cancer group (MLCG) and the UK Medical Research Council Clinical Trials Unit (MRC CTU). (ID 2270)

      10:35 - 10:40  |  Author(s): S. White

      • Abstract
      • Presentation
      • Slides

      Background
      About 40% of all cases of small cell lung cancer (SCLC) occur in the over 70 year age group (70+), and 10% in patients aged over 80 years. A SEER database reports decreasing SCLC 5-year survival with age (7.1%, 3.9% and 2.2% in the <70, 70-79 and 80+ age groups, respectively). However age has been inconsistently reported as a prognostic factor in SCLC trials. Recently a series of randomized trials of chemotherapy (CT) in SCLC were pooled to analyze the prognostic impact of patient sex (Wheatley-Price et al, Annals of Oncology 2009). We used the same dataset to investigate the impact of age.

      Methods
      Five randomized phase II and III CT trials, performed by the MLCG and MRC CTU between 1993 and 2005, were pooled for analysis (one study from the previous analysis was excluded as it did not contain elderly patients). One trial investigated a dose-dense approach and 4 trials compared CT regimens. The primary endpoints were overall survival (OS) in limited stage (LS) and extensive stage (ES) and the rates of haematological and non-haematological toxicity.

      Results
      In total 1439 patients were included, of whom 45% were female and 36% had ES disease. The median age was 63 years (range 30-88), and 343 (24%) were 70+, and only 33 (2%) were 80+. Anthracycline-based CT was given in 61%, versus platinum-based CT in 38% of patients. More patients in the younger group had a good performance status (ECOG 0-1, Karnofsky 80-100); 65% versus 39% (p=0.0007). Baseline hyponatremia was present in 35% and did not differ by age group. Overall, median OS was significantly longer in younger patients in univariate analysis (9.3 months versus 7.4 months; HR 0.79, 95% CI 0.66-0.95, p=0.01). By disease stage, median OS in LS patients was significantly longer in younger patients (HR 0.88, 95% CI 0.79-0.99, p=0.04), and a similar effect was observed in ES (HR 0.75, 95% CI 0.55-1.01, p=0.06). However in multivariate analysis (age, stage, sex, hyponatremia, anemia), factors significantly associated with longer survival were LS, female sex, good PS and absence of hyponatremia, but younger age was no longer prognostic (HR 0.96, 95% CI 0.86-1.08, p=0.52). The elderly were more likely to experience grade 3 or 4 leucopenia (52% versus 40%, p=0.0035), neutropenia (36% versus 31%, p=0.045) and thrombocytopenia (34% versus 22%, p=0.0003), but less likely to experience grade 3 or 4 emesis (8% versus 14%, p=0.022) or mucositis (5% versus 11%, p=0.021). There were no differences in infection rates or blood transfusion rates, although the elderly required more platelet transfusions (p<0.0001). The dose intensity (total number of CT cycles delivered divided by the planned number of cycles) was higher in the younger group (p<0.0001).

      Conclusion
      In a large pooled analysis of CT trials in SCLC, age was not a prognostic factor for survival. However the elderly experienced higher rates of grade 3 and 4 hematological toxicity. Further analysis is ongoing.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-007 - Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel and cisplatin/etoposide in stage III non-small cell lung cancer (ID 1497)

      09:30 - 09:30  |  Author(s): S. White

      • Abstract

      Background
      Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each given with concurrent radiotherapy, remain largely undefined.

      Methods
      Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60Gy chest radiotherapy between 2000-2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student t and chi-squared tests.

      Results
      75 (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs 63 years; p=0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs 14%, p=0.024) and thrombocytopenia (10% vs 0%, p=0.039). Radiation pneumonitis was more common with PC (66% vs 38%, p=0.033). Five treatment related deaths occurred (PC: 3 vs PE: 2, p=1.000). With a median follow up of 51.6 months, there were no significant differences in relapse free survival (median PC 12.0 vs PE 11.5 months, p=0.700) or overall survival (median PC 20.7 vs PE 13.7 months; p=0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. Table 1: Non-hematological and hematological adverse events, by grade (CTCAE 4.0)

      Adverse events PC (n = 44) PE (n = 31)
      n (%) n P~χ2~
      Esophagitis 1 2 3 4 3 (7) 19 (43) 10 (23) 5 (11) 5 (16) 7 (23) 10 (32) 1 (3) 0.151
      Pneumonitis 1 2 3 4 5 21 (48) 6 (14) 0 (0) 1 (2) 1 (2) 4 (13) 6 (19) 1 (3) 1 (3) 0 (0) 0.033
      Neuropathy 1 2 1 (2) 1 (2) 0 (0) 0 (0) 0.485
      Nephropathy 1 2 3 3 (7) 0 (0) 0 (0) 4 (13) 0 (0) 1 (3) 0.314
      Nausea/vomiting 1 2 3 7 (16) 8 (18) 0 (0) 7 (23) 2 (6) 1 (3) 0.291
      Chest infection 1 2 3 4 5 1 (2) 1 (2) 11 (25) 1 (2) 1 (2) 0 (0) 3 (10) 5 (16) 2 (6) 1 (3) 0.534
      Neutropenia 1 2 3 4 4 (9) 5 (11) 6 (14) 0 (0) 2 (6) 0 (0) 8 (26) 4 (13) 0.024
      Febrile neutropenia 3 4 5 (11) 0 (0) 5 (16) 1 (3) 0.394
      Anemia 1 2 3 4 12 (27) 5 (11) 1 (2) 0 (0) 10 (32) 9 (29) 0 (0) 1 (3) 0.117
      Thrombocytopenia 1 2 3 1 (2) 3 (7) 0 (0) 4(13) 1 (3) 3 (10) 0.039
      Treatment-related deaths 3 (7) 2 (6) 1.000

      Conclusion
      PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.