Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
in the first 24 hours, about 20% of the administered dose. The prevention of early
and late emesis was equivalent with both alternatives.
Conclusions: Palonosetron SC administration showed similar AUC0-24h to that of
the IV route, with the same exposure to the drug, and good control in the prevention
of early and late emesis, which can benefit the management of outpatient treatments.
i.v. (mean ± SD)
s.c.
(mean ±SD) p-value
AUC 0-24h (ngxh/ml) 14,10 ± 6,73 12,68 ± 9,70 0,160
Cmax (ng/ml) 11,88 ± 7,38 1,91 ± 1,09 < 0,001
Tmax (h) 0,04 ± 0,04 0,26 ± 0,13 < 0,001
Ae24h (%) 19,48 ± 9,99 22,24 ± 8,50 0,660
Disclosure: All authors have declared no conflicts of interest.
1578P CORRELATION BETWEEN CYCLOPHOSPHAMIDE-INDUCED
HYPONATRAEMIA AND THE USE OF APREPITANT
Y. Tono, T. Mizuno, K. Saito, S. Tamaru, Y. Yamashita, H. Oda, S. Kageyama
and N. Katayama
Medical Oncology, Mie University Hospital, Tsu, JAPAN
Background: For prevention of emesis during anthracyline (A)/cyclophosphamide
(CPA) therapy for breast cancer, use of aprepitant(AP) combined with serotonin
receptor antagonist(5HT3) and dexamethasone(DEX) is recommended. AP, known
to function as a CYP3A4 inhibitor, has been reported to interfere with metabolism of
chemotherapeutic drugs. It has been also reported that AP does not influence the
AUC’s of 4-OH and DCE. Although, in the previous clinical reports for AC, the
toxicities were not significant in patients who were given AP, compared to those
without AP, we have experienced a cases of severe hyponatremia probably related to
AP. Thus, we investigated an impact of AP on Na metabolism during chemotherapy
using CPA for breast cancer.
Material and methods: We investigated serum levels of Na in primary breast cancer
patients who received CPA-combined therapy with the use of AP as anti-emesis, or
not. They all received 600mg/m 2 of CPA combined with either of anthracycline or
docetaxel. Their ages were to be less than 65 years, and their GFR’s were more than
60 ml/min/1.73m 2 . Their prior electrolytes were to be within normal range. In the
first cycle, we evaluated serum Na levels before the CPA start and that at 24 hours
after. We defined serum Na level lower than 135 mEq/L as “hyponatremia” based on
previous study. We enrolled 81 patients, in whom 52 were given AP and 29 were
without AP, between December 2010 and April 2012.
Results: The background between the two groups, with AP and without AP, were
comparable, in whom the median ages were 53.0(33-64) and 53.2(38-65), and the
prior Na levels were139.84 ± 1.89 mEq/L, and 140.25 ± 1.82 mEq/L, in the AP-group
and in non-AP-group, respectively. The uses of 5HT3 and DEX were similar between
the two groups. The incidence of CPA-induced hyponatremia was significantly
higher in AP-group than in non-AP-group (26.9% v 6.9%; P =0.04). The average Na
level at 24 hours after chemotherapy was 136.32 ± 3.73 mEq/L in AP-group, and
138.60 ± 2.92 mEq/L in non-AP-group. Among 14 patients who developed
hyponateremia in AP-group, they were resolved without any intervention in 13, and
one needed Na replacement. The patient did not develop hyponatremia without AP
in the third cycle.
Conclusions: According to our cohort study, AP cause hyponatremia more
frequently in the CPA-combined chemotherapy.
Disclosure: All authors have declared no conflicts of interest.
1579P THE EFFICACY OF TRIPLET ANTIEMETIC THERAPY FOR
CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN
LUNG CANCER PATIENTS RECEIVING HIGHLY EMETOGENIC
CHEMOTHERAPY: PALONOSETRON (PALO), APREPITANT
(APR), AND DEXAMETHASONE (DEX)
H. Yoshizawa 1 ,K.Sato 2 , M. Makino 3 , O. Kobayashi 4 , H. Tanaka 5 , S. Miura 6 ,
S. Watanabe 1 , J. Tanaka 7 , H. Kagamu 6 and N. Ichiei 6
1 Bioscience Medical Research Center, Niigata University Medical and Dental
Hospital, Niigata, JAPAN, 2 Department of Respiratory Medicine, Nagaoka Red
Cross Hospital, Nagaoka, JAPAN, 3 Department of Internal Medicine, Niigata
Prefectural Shibata Hospital, Shibata, JAPAN, 4 Department of Internal Medicine,
Niigata Prefectural Central Hospital, Jyoetsu, JAPAN, 5 Department of Internal
Medicine, Niigata Cancer Center Hospital, Niigata, JAPAN, 6 Department of
Medicine (II), Niigata University Medical and Dental Hospital, Niigata, JAPAN,
7 Department of Health Promotion Medicine, Niigata University Graduate School
of Medical and Dental Sciences, Niigata, JAPAN
Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the
most problematic symptoms experienced by patients undergoing cancer treatments.
Triplet therapy with PALO, APR, and DEX, is a guideline-recommended antiemetic
prophylaxis for highly emetogenic chemotherapy (HEC). However, the efficacy and
safety of this therapy for lung cancer patients has not yet been well investigated.
Methods: Chemotherapy naïve lung cancer patients scheduled to receive HEC were
enrolled in this study. The eligible patients were pretreated with the triplet therapy
(PALO 0.75 mg day 1, APR 125 mg day 1 and 80 mg day 2-3, DEX 9.9 mg day 1 and
8 mg day 2-4) before receiving HEC. The efficacy and safety of these substances were
assessed during an observation period starting from the administration of HEC to
120 hours. A questionnaire diary documented patients’ complaints. The primary
endpoint was the proportion of the patients who did not experience emesis or rescue
antiemetic (Complete Response rate; CR rate) during any part of the whole
observation period. The secondary endpoints were (1) the CR rate during the acute
phase (0-24hrs) and the late phase (24-120hrs), (2) the proportion of patients who
experienced no emetic episodes and significant nausea with no rescue medication
(Complete Control rate; CC rate), and (3) safety.
Results: A total of 72 patients were enrolled with 65 assessable patients at the time of
submission. The median age was 64 years. The CR rate during the whole observation
period, the acute and late phase was 78.5 %, 95.4% and 80.0%, respectively. The CC
rate in the late phase was 62.9%. No severe side effects were observed. In the subset
analysis, the CC rate in late phase was significantly lower in female subset (71.4% vs.
45.0%). Another subset analysis regarding to chemotherapy regimen, the proportion
of vomiting event was higher in the pemetrexed used regimen.
Conclusion: Triplet therapy using PALO, APR and DEX, was shown to be safe and
effective in preventing CINV in lung cancer patients treated with HEC. Further
investigation is needed for to reduce nausea in the late phase.
Disclosure: All authors have declared no conflicts of interest.
1580P PAIN INTERFERENCE OUTCOMES IN A RANDOMIZED
PHASE 3 CLINICAL TRIAL OF DENOSUMAB VS ZOLEDRONIC
ACID (ZA) IN PATIENTS WITH SOLID TUMORS AND BONE
METASTASES
C. Cleeland1 , L. Fallowfield2 , R. von Moos3 , D. Patrick4 , D.H. Henry5 , V. Hirsh6 ,
K. Zarogoulidis7 , A. Feng8 , Z. Cong9 and A. Braun10 1
Symptom Research Division of Internal Medicine, MD Anderson Cancer Center,
Houston, TX, UNITED STATES OF AMERICA, 2 Sussex Health Outcomes
Research & Education In Cancer (shore-c), University of Sussex, Brighton,
UNITED KINGDOM, 3 Medizinische Onkologie und Hämatologie, Kantonsspital
Graubünden, Chur, SWITZERLAND, 4 Health Services, University of Washington,
Seattle, WA, UNITED STATES OF AMERICA, 5 Joan Karnell Cancer Center,
Pennsylvania Hospital, Philadelphia, PA, UNITED STATES OF AMERICA,
6 7
Oncology, McGill University Health Centre, Montreal, QC, CANADA, G.
Papanikolaou Hospital, Pulmonary Department, Aristotle University of
Thessaloniki, Thessaloniki, GREECE, 8 Global Biostatistical Science, Amgen Inc.,
Thousand Oaks, UNITED STATES OF AMERICA, 9 Global Health Economics,
Amgen Inc., Thousand Oaks, CA, UNITED STATES OF AMERICA,
10
Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, UNITED STATES OF
AMERICA
Background: In patients with advanced cancer, bone metastases cause pain and may
lead to skeletal-related events (SREs). Subcutaneous (SC) denosumab prevented SREs
more effectively than intravenous (IV) ZA in patients with solid tumors and bone
metastases in a phase 3 clinical trial (n = 1597; Henry D, J Clin Oncol. 2010. Abstr
9133). We now describe pain interference outcomes for patients with solid tumors in
this trial (ClinicalTrials.gov NCT00330759; May 25, 2006; sponsor Amgen Inc.).
Methods: Patients received 120 mg of denosumab SC or 4 mg of ZA IV every 4
weeks in a randomized, multinational, double-blind, double-dummy trial.
Patient-reported pain interference (overall, activity, and affect) was assessed by the
Brief Pain Inventory (0: does not interfere-10: completely interferes) at baseline (BL)
and upon each monthly visit. Analyses included time to clinically meaningful
(≥2-point increase or decrease from BL) worsening or improvement in pain
interference, and percentage of patients reporting clinically meaningful worsening in
pain interference by visit. Analyses were conducted for patients with no/mild pain
(worst pain 0-4) at BL and all patients at risk.
Results: In patients with no/mild pain at BL, denosumab delayed the median time to
clinically meaningful worsening in pain interference compared with ZA (overall 3.4
months, P = 0.0213; activity 1.8 months, P = 0.0124; affect 0.9 months, P = 0.0518).
Similarly, fewer of these patients treated with denosumab vs ZA reported clinically
meaningful worsening in pain interference over all visits (average relative difference:
overall 13%; activity 16%; affect 10% fewer). Time to clinically meaningful
improvement in pain interference was similar between treatment groups. Pain
interference outcomes were similar among all patients at risk compared to those with
no/mild pain at BL.
Conclusion: In patients with solid tumors, denosumab delayed time to worsening of
pain interference, and fewer patients reported worsening in pain interference over
time, compared with ZA. Greater effects on pain interference were seen for patients
with no/mild pain at BL, suggesting the benefit of early intervention with
denosumab.
Disclosure: C. Cleeland: Advisory board member for Amgen, Genentech, Merck,
and Exelixis, L. Fallowfield: Consultancy honoraria for serving on an advisory board
for Amgen Inc., R. von Moos: Advisory board member for Amgen, Roche, &
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds416 | ix509