Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

A. Gemma



Author of

  • +

    MO24 - NSCLC - Chemotherapy III (ID 110)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO24.10 - Serum iron levels increased by cancer chemotherapy correlate the chemotherapy-induced nausea and vomiting (ID 2080)

      11:25 - 11:30  |  Author(s): A. Gemma

      • Abstract
      • Presentation
      • Slides

      Background
      Despite the introduction of antiemetic treatments including corticosteroids, serotonin (5-HT3) receptor antagonists and neurokinin-1 receptor antagonist, chemotherapy-induced nausea and vomiting (CINV) remains major adverse toxicity of cancer chemotherapy deteriorating patient’s quality of life. It is recommended that these antiemetic treatments should be adopted according to the emetic risk classification of clinical practice guideline, however, the treatments are not so effective in delayed CINV comparing to acute CINV. The mechanism of delayed CINV is not clear so that effective antiemetic drug have not been developed yet. Iron poisoning in cases of blood transfusion or oversupply of iron supplement have various symptoms such as nausea, vomiting, gastroenteritis and liver injury caused by free radical iron, so-called Fenton reaction. We hypothesized that these symptoms are very similar to the adverse effects of cancer chemotherapy and that CINV may be related to the iron level of the patients receiving chemotherapy.

      Methods
      The patients with lung cancer received cytotoxic chemotherapy were included to this study if the serum level of iron, unsaturated iron binding capacity (UIBC ) and ferritin before the chemotherapy, on day 2, and day 8 were available. All chemotherapeutic regimens were administered as standard practice indicated by Japan governmental insurance. The treatment regimens were classified to highly emetogenic chemotherapy (HEC), moderately emetogenic chemotherapy (MEC) and low emetogenic chemotherapy (LEC) according to the clinical practice guideline of the American Society of Clinical Oncology to investigate the relationship between the change of serum iron level and CINV.

      Results
      A total of 37 patients (male26/femal11) were included. The number of patients of each classification were 18 in HEC (cisplatin+etoposide), 14 in MEC(caboplatin+gemcitabine, calboplatin+paclitaxel, calboplatin+etoposide, carboplatin+pemetrexed,irinotecan and amrubicin), 5 in LEC(pemetrexed). Serum iron level (μg/dl) of patients received HEC were 64.6±42.0 before treatment, 233.5±50.0 on day 2, and 235.5±41.3 on day 8. Those of MEC were 62.8±17.0 before treatment, 224.3±33.0 on day 2, and 175.7±87.6 on day 8. Those of LEC were 54.6±17.3 before treatment, 116.4±36.6 on day 2, and 40.7±33.5 on day 8. The serum iron levels of all patients markedly increased on day 2 and there were significant difference between LEC and the other two groups (p=0.01). The iron levels of LEC decreased to normal, on the contrary, those of other two groups remained abnormally high on day 8. With the increase of iron, the significant decrease of UIBC was observed implying that free radical iron appeared after the chemotherapy

      Conclusion
      Serum iron levels were closely correlated to CINV. This phenomenon may be a clue to new approach for antiemetic treatments.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O03 - NSCLC - Targeted Therapies I (ID 113)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      O03.07 - Investigation of risk factors for developing interstitial lung disease (ILD) and poor prognostic factors for ILD death in Japanese patients with non-small-cell lung cancer (NSCLC): a final analysis of a large-scale erlotinib surveillance study (POLARSTAR) (ID 2208)

      11:35 - 11:45  |  Author(s): A. Gemma

      • Abstract
      • Presentation
      • Slides

      Background
      A large-scale surveillance study (POLARSTAR) was implemented to investigate erlotinib safety and efficacy in Japanese patients, focusing on the pattern of occurrence of interstitial lung disease (ILD) and specific factors that may contribute to the onset of ILD in patients receiving erlotinib. The following risk factors for erlotinib-induced ILD have been previously reported: concurrent/previous ILD (adjusted hazard ratio [HR] =3.2), existing emphysema/chronic obstructive pulmonary disease (COPD) (HR=1.9) or lung infection (HR=1.6), smoking status (HR=2.2) and ECOG performance status 2–4 (HR=1.4). These were identified as the primary risk factors for ILD by multivariate analysis. The current analysis was carried out to identify factors linked with poor prognosis in terms of ILD-related death within the POLARSTAR surveillance study.

      Methods
      Enrolment of all patients in Japan receiving erlotinib for NSCLC took place between December 2007 and October 2009; the observation period was 12 months. All ILD-like events were assessed by an independent ILD review committee. ILD was defined as all ILD-like events excluding those events deemed non-ILD by the independent ILD review committee. Risk factors for poor prognosis concerning ILD death were analyzed by multivariate analysis using a logistic regression model.

      Results
      A total of 10,708 patients were enrolled by the data cut-off of 12 October 2009, with data available for 9,909 patients. The majority of ILD cases were reported within 4 weeks of receiving erlotinib. Among the 491 patients who experienced ‘ILD-like’ events, 93 could not be evaluated by the independent ILD review committee due to lack of imaging data; the remaining 398 patients were referred to the committee for evaluation. A total of 310 patients had confirmed ILD by the ILD review committee, based on image evaluation or clinical investigation; 125 had died as a result of ILD. These patients were assessed by multivariate analysis. Sixty-two events were deemed non-ILD and 26 events could not be evaluated due to a lack of clear clinical evidence (e.g. ILD could not be distinguished from progression or pneumonitis, or insufficient imaging data were available). The multivariate analysis identified ECOG performance status 2–4 (adjusted odds ratio [OR] =2.45 [95% CI 1.41–4.27]; p=0.0016), <50% remaining normal lung area (OR=3.12 [1.48–6.58]; p=0.0029) and interstitial pneumonia with concomitant honeycomb lung (OR=6.67 [1.35–32.94]; p=0.02) as poor prognostic factors for ILD death. However, pre-existing interstitial pneumonia by grade of severity was not identified as one of these factors. This result could be attributed to practical bias in this surveillance study, such as selection or treatment bias for patients with pre-existing interstitial pneumonia within the condition of careful dosage specified in the erlotinib label.

      Conclusion
      These final data from this large surveillance study in Japanese patients with recurrent and advanced NSCLC provide further information on the risk factors for poor prognosis with ILD, identifying those patients at greatest risk of ILD-related death. Improved awareness of these prognostic factors will help clinicians in monitoring those patients at highest risk.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      O15.05 - Randomized Phase III Trial of S-1 plus Cisplatin versus Docetaxel plus Cisplatin for Advanced Non-Small-Cell Lung Cancer (TCOG0701): Subgroup Analysis. (ID 1895)

      11:15 - 11:25  |  Author(s): A. Gemma

      • Abstract
      • Presentation
      • Slides

      Background
      Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced non-small cell lung cancer (NSCLC). S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Molecularly targeted agents including bevacizumab (BEV) have shown activity and safety in non-squamous (non-Sq) NSCLC.

      Methods
      Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m[2]/day (40 mg/m[2] b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m[2] on day 8 every 5 weeks or docetaxel 60 mg/m[2 ]on day 1 plus cisplatin 80 mg/m[2] on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was <1.322. Secondary endpoints included progression-free survival (PFS), response, safety, and QOL. Subgroup analysis by histology (non-Sq vs Sq) was conducted.

      Results
      From April 2007 through December 2008, 608 patients were randomly assigned to SP (n=303) or DP (n=305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Non-Sq and Sq patients in SP/DP arm was 251/247 and 50/48 respectively. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR=1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was better in the SP arm (repeated measures ANOVA: p<0.01). Subgroup analysis by histology revealed that the median OS of non-Sq and Sq patients in SP/DP group was 17.4/19.1 months and 12.3/11.7 months respectively, of which hazard ratio was 0.973 (95% CI, 0.797-1.187) and 1.239 (95% CI, 0.819-1.874). Interaction P value was 0.3004.

      Conclusion
      S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC both non-Sq and Sq histology. Favorable toxicity profile of the SP regimen and encouraging outcome in patients with non-Sq prompted us to conduct a prospective study of SP plus BEV and maintenance S-1 BEV for non-SQ currently underway.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P3.10-045 - Combination chemotherapy with bevacizumab, docetaxel and carboplatin for chemotherapy-naive patients with non-squamous cell lung carcinoma: Phase II study. (ID 2660)

      09:30 - 09:30  |  Author(s): A. Gemma

      • Abstract

      Background
      Some clinical studies suggested a possible advantage of bevacizumab combined with taxanes. Although carboplatin is slightly inferior to cisplatin in terms of survival, addition of bevacizumab to carboplatin may overcome this disadvantage. The aim of this study was to clarify the efficacy and safety of combination chemotherapy consisting of bevacizumab, docetaxel and carboplatin in the 1st line chemotherapy for non-squamous non-small cell lung cancer.

      Methods
      Patients who are untreatable with thoracic curative radiotherapy, with stage IIIB/IV non-squamous non-small cell lung cancer, age ranging from 20 to 74 years, PS 0 or 1, adequate organ functions, measurable lesions, and written informed consents were eligible. Combination chemotherapy consisting of bevacizumab (15 mg/kg), docetaxel (60 mg/m2) and carboplatin (AUC=6) on day 1 was administered every 3 weeks up to 6 cycles (induction phase). Unless PD, bevacizumab maintenance therapy was performed until PD (maintenance phase). The primary endpoint was median PFS to prove its superiority to the previous standard combination chemotherapy consisting of docetaxel and cisplatin with its historical median PFS of 4.6 months. With =0.05 and =0.20, calculated minimum sample size was 37, and the final determined sample size was 40. This trial was registered to the clinical trial registration system with the ID of UMIN000004524.

      Results
      Forty patients enrolled and 39 patients were analyzed. They included women in 31%, patients with PS of 0 in 67%, stage IV in 92%, EGFR mutations in 13% and unknown EGFR status in 8%. The median age was 62 years. The induction phase was delivered for 4 cycles in median (range: 1-6), and 21 patients (54%) received maintenance phase with median 4 cycles (range: 2-24). Frequent toxicities ≥ grade 3 during the induction phase in completely analyzed patients (n=32) included neutropenia (50.0%), anemia (9.4%), thrombocytopenia (9.4%), febrile neutropenia (25.0%) and hypertension (37.5%). Other toxicities ≥ grade 3 were cholecystitis, increased ALP, hyperpotassemia, proteinuria, diarrhea, appetite loss, nausea, constipation, infection, stomatitis, and cancer pain in 3.1%, respectively. Interim external reviews of 35 pts revealed ORR of 74% (26/35) and median PFS of 6.4 months (95% CI: 4.8-9.9).

      Conclusion
      The primary endpoint was met because the lower end of the 95%CI exceeded the threshold of 4.6 months. This combination chemotherapy seems promising in terms of safety and effectiveness, warranting phase III studies.