Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-015 SYSTEMIC INFLAMMATION ALTERS CARBOPLATIN
PHARMACOKINETICS EXPLAINING POOR SURVIVAL IN ADVANCED
LUNG CANCER PATIENTS
Benjamin Harris 1 , Viet Phan 2 , Vidya Perera 3 , Anneliese Szyc 4 , Peter Galettis 5 ,
Philip Beale 6 , Andrew Mclachlan 4 , Stephen Clarke 7 , Kellie Charles 1
1 Discipline of Pharmacology, University of Sydney, Camperdown/Australia,
2 Concord Repatriation General Hospital, Concord/NSW/Australia, 3 School of
Pharmacy and Pharmaceutical Sciences, Suny at Buffalo, Buffalo/United States of
America, 4 Faculty of Pharmacy, University of Sydney, Camperdown/NSW/Australia,
5 Discipline of Clinical Pharmacology, University of Newcastle, Newcastle/NSW/
Australia, 6 Concord Cancer Centre, Concord Repatriation General Hospital,
Concord/NSW/Australia, 7 Department of Medical Oncology, Royal North Shore
Hospital, St Leonards/NSW/Australia
Background: Advanced cancer patients with elevated systemic inflammatory
markers have significantly poorer chemotherapy response and shorter overall
survival compared to patients without inflammation. However, mechanisms
underlying this association are unclear. There is an urgent need to identify
these mechanisms as a high proportion of advanced cancer patients present
with systemic inflammation (~25%). This study aimed to determine the impact
of inflammatory status, as determined by the neutrophil-to-lymphocyte ratio
(NLR), on drug pharmacokinetics and clinical outcomes, including patient
toxicity, chemotherapy cycles received, response and survival, in patients
with advanced non-small cell lung cancer (NSCLC). Methods: Seventy-two
advanced NSCLC patients were recruited for a planned 6 cycles of carboplatin
(target AUC 6 mg/mL•min) and paclitaxel (175mg/m 2 ) chemotherapy. Drug
concentrations from the first chemotherapy cycle were measured and
analysed using population pharmacokinetic modelling. Clinical data and
pharmacodynamic endpoints were also collected. Univariate analysis and
multivariable regression analysis was used to identify relationship between
NLR status (NLR ≤ 5 and NLR > 5) to pharmacokinetic parameters and clinical
outcomes. Results: Patient demographics were not different between low
and high NLR groups except for nutritional status. Patients with NLR > 5
had increased carboplatin exposure but no associations were found with
paclitaxel pharmacokinetics. Increased carboplatin exposure associated
with increased toxicities. Patients with elevated inflammation had serious
clinical consequences including dose-limiting toxicities leading to reduced
cycles of first-line chemotherapy, poor response and shorter overall survival.
Conclusion: Advanced NSCLC patients with elevated inflammation have
alterations in drug pharmacokinetics that may be negatively impacting their
clinical outcomes. This under-appreciated inflammatory-mediated change
in pharmacokinetics is a potential source of inter-individual variability that
may be reduced by dose individualisation according to inflammatory status.
Future trials of this approach need to be investigated to assess the impact
on survival in advanced cancer populations treated with platinum-based
chemotherapy.
Keywords: biostatistics, pharmacokinetics, Biomarkers, inflammation
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-016 WEEKLY PACLITAXEL WITH 4 WEEKLY CARBOPLATIN
AS SALVAGE TREATMENT IN ADVANCED NON-SMALL CELL LUNG
CANCER- HCG CENTRE EXPERIENCE
Satheesh Thungappa, Shekar Patil, H Shashidhara
Medical Oncology, Hcg Bangalore Institute of Oncology Speciality Centre,
Bangalore/India
Background: Progress has been made in the treatment of non-small cell lung
cancer (NSCLC) over past 40 years. Chemotherapy can prolong survival in
the patients with advanced NSCLC with newer supportive care availability.
Newer advances include Histology, targeted therapy with the help of next
generation sequencing (NGS) and Immunotherapy. Immunotherapy is
not feasible in most of our patients in India after failure to first two line
chemotherapy; hence this study was conducted to evaluate the efficacy and
toxicity of weekly paclitaxel and 4 weekly Carboplatin as salvage regimen.
Methods: The NSCLC patients(42) failure to previous 2 lines of chemotherapy
including targeted agents were treated with salvage regimen weekly
Paclitaxel 70- 80 mg/m2 3 weeks / 1 week gap and 4 weekly Carboplatin- AUC 5
with Growth factor support at HCG, Bangalore from Jan 2014 to june 2015. The
efficacy and toxicity of above regimen were analyzed Results: Of 42 patients
male: Female ratio 2.5:1, median age-59, 66.6%, were Adenocarcinoma, 19%
had EGFR mutations. Objective response: Partial Response (PR)) was seen in
14.28%, Stable disease (SD) in 28.57% and progressive disease (PD) in 57.14%.
Median progression free survival (PFS) 3.5 months, mean overall Survival (OS)
9.5 months.
Prior therapy for
NSCLC
Prior EGFR
inhibitor
+1 line
Chemo(N-8)
Prior 2 lines
of Chemo
(n-27)
Prior 3 lines of
chemo (n-7)
PR 37.5% 11.1% -
SD 37.% 29.62% 14.2%
PD 25% 59.25% 85.7%
Median PFS in
months
7 4 3
Median OS in
months
15 10 8
Hematological toxicity: anemia (38% grade 1-2), neutropenia (28.57%
grade 1-2), Febrile neutropenia (9.5%), thrombocytopenia (31%-Gr-1-2).
Nonhematological toxicity: peripheral neuropathy (38% grade 1-2), Alopecia
88%, Mucositis 23.8%(Gr 1-2), Nausea/vomiting 16.6%, Diarrhea 9.52% and
discontinuation due to severe peripheral neuropathy -7.1% Conclusion: Weekly
Paclitaxel with 4 weekly Carboplatin is feasible, active and tolerable salvage
regimen in previously treated NSCLC.
Keywords: salvage, Eficacy, NSCLC
POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
CLINICAL TRIALS –
TUESDAY, DECEMBER 6, 2016
P2.03A-017 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
(CINV) IN ITALIAN LUNG CANCER PATIENTS: ASSESSMENT BY
PHYSICIAN, NURSE AND PATIENT
Simona Carnio 1 , Domenico Galetta 2 , Vieri Scotti 3 , Diego Luigi Cortinovis 4 ,
Andrea Antonuzzo 5 , Salvatore Pisconti 6 , Antonio Rossi 7 , Olga Martelli 8 , Alice
Lunghi 9 , Sara Pilotto 10 , Alessandro Del Conte 11 , Valeria Pegoraro 12 , Elisabetta
Sara Montagna 2 , Juliana Topulli 3 , Davide Pelizzoni 4 , Simonetta Grazia
Rapetti 1 , Martina Gianetta 1 , Maria Vittoria Pacchiana 1 , Silvia Novello 1
1 Department of Oncology - University of Turin, Thoracic Oncology Unit, Orbassano/
Italy, 2 Clinical Cancer Center “Giovanni Paolo Ii”, Bari/Italy, 3 Department of
Oncology, Radiation Therapy Unit, Careggi University Hospital, Florence/
Italy, 4 Medical Oncology Unit, San Gerardo Hospital, Monza/Italy, 5 Division of
Medical Oncology, Department of Oncology, S. Chiara University Hospital, Pisa/
Italy, 6 Department of Oncoematology Medical Oncology, S.G. Moscati Hospital
of Taranto, Taranto/Italy, 7 Division of Medical Oncology, S.G. Moscati Hospital,
Avellino/Italy, 8 Medical Oncology Unit, San Giovanni Addolorata Hospital, Rome/
Italy, 9 Department of Oncology, Medical Oncology Unit, Careggi University
Hospital, Florence/Italy, 10 Medical Oncology, Department of Medicine, Verona
University Hospital, Verona/Italy, 11 Department of Medical Oncology, Azienda Per
L’Assistenza Sanitaria No. 5 - Friuli Occidentale, Presidio Ospedaliero Di Pordenone,
Pordenone/Italy, 12 Ims Health Information Solutions Italy Srl, Milan/Italy
Background: Despite therapeutic advances, CINV still represents a common
side-effect of chemotherapy and often its perception is not equal between
patients and healthcare professionals. Aims of this study were to evaluate
the agreement degree among clinicians, patients and nurses about CINV
and other relevant items, and to understand whether anxiety, as well as
other demographical and treatment-related factors, could play a role in
CINV development. Methods: A dedicated survey was designed in agreement
with a psychologist: 11 aspects (anxiety, mood, weakness, appetite, nausea,
vomiting, pain, somnolence, breath, general status, and trust in treatments)
were investigated through Numerical Rating Scale in four consecutive
evaluations (T0, T1, T2 and T3) during first-line chemotherapy. From
August 2015 to February 2016, the survey was administered in 11 Oncologic
Institutions to 188 stage III/IV lung cancer patients and to their oncologists
and nurses. Clinician versus patient (CvP), nurse versus patient (NvP) and
clinician versus nurse (CvN) agreements were estimated in relation with the
investigated items, applying Weighted Cohen’s kappa and the grid of Landis
and Koch. A multivariate logistic model was applied to evaluate factors
possibly influencing anticipatory CINV development as perceived by patients
before initiating chemotherapy (T0). Generalized Equation Estimates (GEE)
for repeated measures were used to evaluate factors possibly influencing
CINV development overall at T1, T2 and T3. Results: The incidence of CINV as
reported by patients varied from 40.3% at T0 to 71.3% at T3. Both CvP and
NvP concordances on the investigated items were mainly moderate, slightly
increasing over time and becoming substantial for some items, in particular
when evaluating NvP concordances. Pre-chemotherapy anxiety in all its mild
(Odds Ratio [OR]: 4.99; 95% Confidence Interval [CI]: 1.26 – 19.81), moderate
(OR: 4.89; 95% CI: 1.29; 18.50) and severe (OR: 4.70; 95% CI: 1.10; 19.98)
manifestations, as well as mild (OR: 10.02; 95% CI: 3.27; 30.64), moderate (OR:
11.23; 95% CI: 3.54; 35.67) and severe (OR: 12.86; 95% CI: 2.83; 58.48) anxiety
Copyright © 2016 by the International Association for the Study of Lung Cancer
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