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Annals of Oncology
cost-effectiveness have been evaluated as an additional study. We analyzed impact of
prolonged treatment with capecitabine on patients’ HRQOL.
Methods: Capecitabine (2500 mg/m 2 /day) was orally given on days 1-14, followed by
a 7-day rest. Enrolled patients were randomly assigned to group A (received 8
courses of capecitabine) or group B (16 courses). In patients agreed to participate to
the additional study, HRQOL was evaluated by self-administered questionnaire at the
start of the protocol treatment, 3, 6, 9, 12, 15 and 18 months. The questionnaire
includes Functional Assessment of Cancer therapy-C (FACT-C) and EuroQol 5
Dimension (EQ-5D).
Results: In 1306 patients enrolled to the JFMC37-0801 trial, HRQOL of 171
participants (81 in group A, 90 in group B) were evaluated. Mean age of the patients
in group A and B was 63.3 and 64.5 years-old, respectively. Among a total of 1197
points of survey, 959 questionnaires (80.1%) were retrieved. Recovery rates of
questionnaires tended to decrease with time after finishing treatment. Through the
entire survey period, mean score of FACT-C (96.9-103) and EQ-5D (0.85-0.93) were
satisfactory. In longitudinal analysis of the change from baseline score, the scores
tended to increase after finishing the treatment period in both group A and group
B. Significant difference between the score of group A and group B was not observed
in each survey point. No difference by age and tumor stage was also observed.
Conclusions: HRQOL of the patients received postoperative adjuvant chemotherapy
with capecitabine was satisfactory through the survey period. There was no
significant difference of HRQOL between 8 and 16 courses of capecitabine treatment.
Disclosure: J. Sakamoto: Junichi Sakamoto is a director of the Japanese Foundation
for Multidisciplinary Treatment of Cancer (JFMC). S. Saji: Shigetoyo Saji is a director
of the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC). All
other authors have declared no conflicts of interest.
589P SURVIVAL ANALYSIS OF 1,061 PATIENTS WITH
SYNCHRONOUS COLORECTAL HEPATIC METASTASES
J. Xu, Y. Zhong, D. Zhu, Y. Wei, L. Ren
Department of General Surgery, Zhongshan Hospital Fudan University,
Shanghai, CHINA
Objectives: To investigate survival and to identify prognostic factors in patients with
synchronous colorectal hepatic metastasis.
Methods: Clinical, pathologic and follow-up data were retrospectively collected from
1,061 consecutive patients treated for synchronous colorectal hepatic metastases at
Zhongshan Hospital between 2000 and 2010. The prognostic values of different
factors were studied through univariate and multivariate analyses.
Results: For patients with resectable hepatic metastases, the total expense per patient
in the simultaneous resection group was lower than that in the staged resection
group (25,693 RMB vs. 34,129 RMB, P < 0.050), and there were no significant
differences in the complication rates (24.5% vs. 20.5%) or median overall survival
(48.5 vs. 47.0 months) between the simultaneous and staged resection groups. For
patients with unresectable hepatic metastases, resection of the primary tumor was
associated with improved median overall survival (19.0 vs. 9.3 months, P < 0.001). Six
factors were found to be independent predictors of poor survival by multivariate
analysis: a poorly differentiated primary tumor, number of hepatic metastases ≥ 4,
maximum hepatic metastasis size ≥ 5 cm, extra-hepatic metastases, no resection of
the primary tumor and no surgical treatment of hepatic metastases. Giving one point
to each of the above factors, all of the patients were divided into low-risk (0-1
points), medium-risk (2-3 points) and high-risk (4-6 points) groups with 5-year
survival rates of 51%, 16% and 0%, respectively (P < 0.001).
Conclusions: Simultaneous resection of the primary tumor and hepatic metastases
were accepted as prognostic factors in patients with resectable synchronous colorectal
hepatic metastases. Resection of the primary tumor was recommended at the right
time for asymptomatic patients with unresectable hepatic metastases. A prediction
model using the above six factors can be used to guide the clinical management of
patients with synchronous colorectal hepatic metastases.
Disclosure: All authors have declared no conflicts of interest.
590P PHASE 1B STUDY OF A NOVEL ORAL PPAR-GAMMA
AGONIST, EFATUTAZONE IN COMBINATION WITH FOLFIRI IN
JAPANESE PATIENTS WITH METASTATIC COLORECTAL
CANCER WHO FAILED THE FIRST-LINE THERAPY
T. Yoshino 1 , S. Yuki 2 , K. Yamazaki 3 , N. Machida 3 , Y. Komatsu 4 , R. Oyama 5 ,
Y. Yachi 5 , H. Onuma 5 , A. Ohtsu 6
1 Department of Gastroenterology & GI Oncology, National Cancer Center
Hospital East, Kashiwa, JAPAN, 2 Department of GI, Hokkaido University
Hospital, Hokkaido, JAPAN, 3 Division of Gastrointestinal Oncology, Shizuoka
Cancer Center, Shizuoka, JAPAN, 4 Cancer Center, Hokkaido University Hospital,
Hokkaido, JAPAN, 5 Clinical Developmental Department II, Daiichisankyo CO.,
LTD, Tokyo, JAPAN, 6 Research Center for Innovative Oncology, National Cancer
Center Hospital East, kashiwa, JAPAN
Background: Efatutazone is a highly-selective peroxisome proliferator-activated
receptor gamma (PPAR-gamma) agonist of thiazolidinedione (TZD) class, which
shows higher potency than rosiglitazone. The recommended dose (RD) is 0.50 mg
twice-daily (BID) in accordance with pharmacokinetics (PK), pharmacodynamics
(PD, adiponectin) and safety analyses in US and Japanese phase 1 studies. This study
assessed the safety, tolerability, antitumor activity, PK, PD, and determined the RD
of efatutazone in combination with FOLFIRI in Japanese patients.
Materials and methods: This was an open-label, dose-escalation study using a 3 + 3
design. Each patient participated in only 1 dose group and received oral efatutazone
0.25 or 0.50 mg BID with every 2-week administration of FOLFIRI (Irinotecan 180
mg/m 2 IV infusion over 90 minutes,l-LV 200 mg/m 2 IV infusion over 120 minutes,
and 5-FU IV continuous infusion 2400 mg/m 2 over 46 hours). After determining the
RD of efatutazone, 9 additional patients were enrolled for the further assessment of
efatutazone. PK samples for efatutazone, Irinotecan and SN-38 were collected to
assess the drug–drug interaction. PD samples were also collected. All patients
provided written informed consent.
Results: A total of 15 patients were enrolled (7 male and 8 female; median age of 63
years old, range: 41–73 years). Dose-limiting toxicities were not observed, and the
maximum tolerated dose (MTD) was not reached. Most patients experienced edema
(80.0%) and weight increase (100.0%) which were manageable with diuretics. The
most common haematological toxicities were neutropenia and anaemia, managed
with supportive therapy and/or modification of FOLFIRI. Seven out of 15 patients
showed stable disease (SD). Efatutazone increased plasma adiponectin levels. Plasma
concentration of efatutazone increased according to dose. Efatutazone doesn’t affect
plasma concentration of Irinotecan and SN-38.
Conclusions: Efatutazone in combination with FOLFIRI is a novel anticancer
therapy, which is tolerated in Japanese patients with metastatic colorectal cancer.
Although the MTD was not reached, 0.50 mg BID, corresponding to the RD in
western patients, was selected as the RD for Japanese patients based on safety
analyses. Full safety data and clinical activity data will be presented.
Disclosure: T. Yoshino: I have honoraria with Chugai, Takeda, Bristol-Myers
Squibb, Yakult and Merck Serono. I have research funding from Bayer,Taiho,
Daiichi-sankyo and Quintiles. I have received consulting fee from Takeda. Y.
Komatsu: Y.Komatsu has honoraria with DAIICHI SANKYO COMPANY,
LIMITED, YAKULT HONSHA CO., LTD, Pfizer. Y.Komatsu has research
funding from DAIICHI SANKYO COMPANY, LIMITED, YAKULT HONSHA
CO., LTD, Pfizer. R. Oyama: R.Oyama is an employee of Daiichisankyo CO.,
LTD. Y. Yachi: Y.Yachi is an employee of Daiichisankyo CO.,LTD. H. Onuma:
H.Onuma is an employee of Daiichisankyo CO., LTD. A. Ohtsu: A.Ohtsu has an
advisory role and/or honoraria with Takeda Pharmaceutical Co., Ltd, DAIICHI
SANKYO, Novartis, CHUGAI PHARMACEUTICAL CO., LTD, TAIHO
Pharmaceutical Co., Ltd, Glaxosmithkline, Pfizer, YAKULT HONSHA, Merck
Serono, Bristol-Myers Squibb. All other authors have declared no conflicts of
interest.
591P COLON CANCER ADJUVANT MFOLFOX-6 – SURVIVAL IMPACT
OF OXALIPLATIN REDUCED DOSE-INTENSITY
A.F. Carneiro 1 , J. Godinho Bexiga 1 , D.S. Marques 1 , C. Faustino 1 , N. Sousa 2 ,
M. Machado 2 , P. Ferreira 1 , A. Raimundo 1 , R. Fragoso 1
1 Medical Oncology, Instituto Portugues de Oncologia Centro do Porto, Porto,
PORTUGAL, 2 Medical Oncology/Hematology, Instituto Portugues de Oncologia
Centro do Porto, Porto, PORTUGAL
Background: Adjuvant colon cancer treatment may include the oxaliplatin/
fluoropirimidine combination. This association has shown benefit on progression free
survival (PFS) and overall survival (OS) compared to fluoropirimidine monotherapy
in these patients. Adverse events are frequent and may cause delay on treatment
delivery or drug dose reduction. The survival impact of oxaliplatin reduced dose
intensity (RDI) is unknown.
Objective: Evaluation of survival impact of oxaliplatin RDI in colon cancer
patients treated with adjuvant mFOLFOX-6. Material and methods: A consecutive
series of colon cancer patients treated with adjuvant mFOLFOX-6 at our
institution between 09/2004 and 11/2009. The impact of Oxaliplatin < 75%
(group A) and ≥ 75% (group B) on PFS and OS was estimated with a Cox
Proportional Hazards model.
Results: There were no differences in age, sex, ECOG, comorbidity, histologic grade
and stage distribution between groups. Two hundred and seventy seven (277)
patients were identified (53% in group A). Fifty nine percent (59%) of patients
completed the 12 mFOLFOX-6 cycles and the median duration of adjuvant
chemotherapy was 6,5 months. The mean oxaliplatin dose-intensity was 71%
(median 74%). Adverse events led to dose reduction and drug suspension in 53%
and 40% of patients, respectively. There were 3 deaths during treatment. The main
causes to RDI were grade ≥ 3 hematologic toxicity (47%) and neuropathy (12%) –
median cumulative oxaliplatin dose at first neurologic severe event was 1024 mg.
There were no differences in PFS and OS between RDI groups, neither after stage
stratification.
Conclusion: In our cohort patient’s characteristics and toxicity profile were similar
to published trials. FOLFOX conclusion rate was inferior than the described in
MOSAIC trial (59% vs 74,7%). Despite the inferior accomplishment rate, there was
no impact in PFS and OS in oxaliplatin RDI < 75% group.
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix201