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692P PRELIMINARY SAFETY DATA FROM A RANDOMIZED PHASE
II STUDY COMPARING DOSE-ESCALATED WEEKLY
PACLITAXEL VERSUS STANDARD-DOSE WEEKLY
PACLITAXEL FOR PATIENTS WITH PREVIOUSLY TREATED
ADVANCED GASTRIC CANCER
S. Yuki1 , K. Shitara2 , D. Takahari2 , M. Nakamura3 , C. Kondo2 , T. Tsuda4 ,T.Kii5 ,
Y. Tsuji6 , I. Oze7 , K. Muro2 1
Department of Gastroenterology, Hokkaido University Hospital, Sapporo,
JAPAN, 2 Department of Clinical Oncology, Aichi Cancer Center Hospital,
Nagoya, JAPAN, 3 Department of Gastroenterology, Sapporo City General
Hospital, Sapporo, JAPAN, 4 Department of Clinical Oncology, Saint Marianna
University School of Medicine, Kawasaki, JAPAN, 5 Cancer Chemotherapy
Center, Osaka Medical College, Osaka, JAPAN, 6 Department of Medical
Oncology, KKR sapporo medical center Tonan hospital, Sapporo, JAPAN,
7
Division of Epidemiology and Prevention, Aichi Cancer Center Research
Institute, Nagoya, JAPAN
Background: Recently, we studied the effects of neutropenia occurring during
second-line chemotherapy with weekly paclitaxel in a retrospective analysis of 242
patients with advanced gastric cancer, and observed better survival among patients
with neutropenia compared to patients without neutropenia (Shitara K, et al. Annals
of Oncol. 2011). Therefore, we conducted a multi-institutional, open-label,
randomized phase II trial comparing dose-escalated weekly paclitaxel with dose
adjustments determined by degree of neutropenia versus standard-dose weekly
paclitaxel for patients with previously treated advanced gastric cancer (protocol ID
UMIN000004055).
Patients and methods: Patients with advanced or recurrent gastric cancer that
progressed during one or more previous chemotherapy regimens were included.
Ninety patients were randomized to a standard dose of weekly paclitaxel (80 mg/m 2 ,
Arm A) or an escalated dose of weekly paclitaxel (80 mg/m 2 on day 1, 100 mg/m 2 on
day 8, and 120 mg/m 2 on day 15 unless severe toxicity is observed, Arm B). The
primary endpoint was overall survival. Secondary endpoints included objective
response rate, disease control rate, progression-free survival, and adverse events. We
present the preliminary safety data from the first 8 weeks.
Results: From September 2010 to November 2011, a total of 90 patients were
enrolled at 13 institutions. One patient in Arm B did not receive paclitaxel. The dose
of paclitaxel was escalated to 100 mg/m 2 in 41 patients (91.1%) and then to 120 mg/
m 2 in 29 patients (64.4%) in Arm B. In the first 8 weeks, 25 (55.5%) patients in Arm
A patients and 20 (46.7%) patients in Arm B required dose reduction or treatment
delay. Frequencies of grade 1 or more neutropenia were 66.7% in Arm A and 86.4%
in Arm B, and grade 3 or more neutropenia frequencies were 31.1% in Arm A and
38.6% in Arm B. Grade 1 or more sensory neuropathy frequencies were 55.6% in
Arm A and 68.1% in Arm B. Two patients in Arm A and one patient in Arm B
experienced febrile neutropenia. No treatment-related deaths occurred.
Conclusions: Preliminary safety data during the first 8 weeks of treatment indicate
comparable compliance between the two arms, despite the substantial number of
patients who underwent dose escalation.
Disclosure: All authors have declared no conflicts of interest.
693P EFFICACY AND SAFETY OF DOSE-DENSE CHEMOTHERAPY
WITH MODIFIED TCF REGIMEN (TCF-DD) IN ELDERLY
PATIENTS WITH METASTATIC GASTRIC CANCER (MGC)
G. Tomasello, W. Liguigli, S. Lazzarelli, R. Poli, F.M. Negri, L. Toppo, M. Ratti,
M. Brighenti, F. Gerevini, R. Passalacqua
Oncology Division, Istituti Ospitalieri di Cremona, Cremona, ITALY
Background: GC is more common in elderly patients (pts). Most oncologists are
reluctant to treat this pts population with the most active poli-chemotherapy
combinations because of safety concerns. Subgroup analysis of elderly pts enrolled in
European studies show limited and conflicting data. We previously reported on the
feasibility and high activity of a dose-dense TCF regimen (TCF-dd) (Tomasello
2010). This study aims to evaluate the efficacy and safety of this schema in the
elderly pts subgroup (≥ 65 years).
Methods: From 11/04 to 05/12, 111 consecutive pts with MGC (median age 65,
range 31-81) were enrolled in a single-centre phase II study. Pts received Docetaxel
70 mg/m 2 d1, CDDP 60 mg/m 2 d1, l-AF 100 mg/m 2 d1-2 followed by 5-FU 400 mg/
m 2 bolus d1-2, and then 600 mg/m 2 as a 22h c.i. d1-2, q2w, plus G-CSF d3. Pts ≥
65y (56) received the same schedule reduced by 30%.
Results: 96 pts evaluable for response and all for toxicity. In pts ≥ 65y we observed 4
CR (7%) 25 PR (45%) 10 SD (18%) 7 PD (13%); in younger pts: 2 CR (4%) 30 PR
(55%) 9 SD (16%) 9 PD (17%); ORR by ITT 56% (95% IC 45-64). Median OS was
11.9 months (9,4-14,8); in elderly and younger pts 11,2 (8,4-11,1) and 12,7 (9-16,5)
respectively. Out of 48 evaluable pts ≥ 65y, 26 (54%) were treated at full doses
without any delay. In the elderly most frequent G3-4 toxicities were neutropenia
(14%) thrombocytopenia (15%) febrile neutropenia (7%) asthenia (27%) and
hypokalemia (17%); in the younger: neutropenia (56%) thrombocytopenia (21%)
febrile neutropenia (16%) asthenia (43%) hypokalemia (21%).
Annals of Oncology
Conclusions: This study shows that elderly pts can be treated with a TCF-dd
regimen reduced by 30% achieving similar efficacy results of younger patients with
lesser toxicity.
Disclosure: All authors have declared no conflicts of interest.
694P PROGRESSION-FREE SURVIVAL AND POSTPROGRESSION
SURVIVAL IN PATIENTS WITH ADVANCED GASTRIC CANCER
TREATED WITH FIRST-LINE CHEMOTHERAPY
K. Shitara 1 , K. Matsuo 2 , K. Muro 3 , A. Ohtsu 1
1 Gastroenterology & Gastrointestinal Oncology, National Cancer Center Hospital
East, Kashiwa, JAPAN, 2 Aichi Cancer Center Research Institute, Aichi Cancer
Center, Nagoya, JAPAN, 3 Clinical Oncology, Aichi Cancer Center Hospital,
Nagoya, JAPAN
Background: Progression-free survival (PFS) has been reported to be moderately
correlated to overall survival (OS) in patients with advanced gastric cancer (AGC) who
received first-line chemotherapy (Shitara, K et al. Invest New Drug 2011; Shitara K
and Burzykowski T. On behalf of GASTRIC. ASCO 2011). Impact of post progression
survival (PPS) on OS of patients with AGC has not yet been reported in detail.
Methods: We retrospectively analyzed AGC patients who received first-line
chemotherapy including fluoropyrimidine plus platinum with confirmed disease
progression. We partitioned OS into PFS and PPS and analyzed the correlation
between OS and either PFS or PPS by Spearman rank correlation coefficient (r).
Subgroup analyses were performed according to treatment setting (clinical trial or
practice) and presence of measurable lesion. Multivariate analysis was also conducted
to evaluate prognostic factors for PPS.
Results: Between April 2005 to May 2011, 291 AGC patients met inclusion criteria.
One-hundred five patients (36%) included in clinical trials and 246 patients (85%)
received second-line chemotherapy. Median PFS, PPS, and OS were 5.3 months, 8.1
months. 14.8 months, respectively. PFS and OS showed a correlation with r of 0.75 (95%
CI, 0.69- 0.81). PPS and OS also showed a correlation with r of 0.87 (95% CI, 0.84- 0.91).
Correlations tend to be higher between PSS and OS than that of PFS and OS in subset of
patients in clinical trials (r = 0.84 vs. r = 0.72) or patients with measurable lesion (r = 0.87
vs. r = 0.72). According to the multivariate analysis, performance status at progression and
second-line chemotherapy were significantly associated with length of PPS.
Conclusion: Our results indicate that both PFS and PSS is correlated with OS in
first-line chemotherapy for advanced AGC, thus suggest the importance of reporting
detailed patients characteristic and treatment course after disease progression in
clinical trials of first-line chemotherapy for AGC.
Disclosure: All authors have declared no conflicts of interest.
695P QUALITY OF LIFE IN FLAGS TRIAL A RANDOMIZED,
COMPARATIVE, OPEN LABEL, MULTICENTER, PHASE 3 OF
S-1 + CISPLATIN (CS) COMPARED TO 5-FU + CISPLATIN (CF)
IN UNTREATED ADVANCED GASTRIC CANCER (AGC)
PATIENTS
G. Bodoky 1 , A. Carrato 2 , A. Ravaioli 3 , J.A. Ajani 4
1 Dept of Medical Oncology, Szent Laszlo Korhaz, Budapest, HUNGARY,
2 Medical Oncology, Hospital Ramon y Cajal, Madrid, SPAIN, 3 Primario
Oncologia Medica, Ospedale “Infermi” di Rimini, Rimini, ITALY, 4 Gastrointestinal
Medical Oncology, MD Anderson, Cancer center, Houston, TX, UNITED STATES
OF AMERICA
Background: FLAGS’ primary objective was overall survival. We report below the
Patient-Reported Outcomes (PRO) (i.e., Quality-of-Life [QoL]) which was one of the
secondary objectives.
Methods: All patients who completed at least one PRO assessment were eligible for
analysis. The primary PRO endpoint was the Trial Outcome Index (TOI) of the
Functional Assessment of Cancer Therapy – Gastric (FACT-Ga). Patients completed
the FACT-Ga at the beginning of Cycles 1, 2, 3, 4, 6 and then every 3 cycles prior to
treatment administration. All individual subscales in the FACT-Ga were also
evaluated as secondary endpoints. The Chemotherapy Convenience and Satisfaction
Questionnaire (CCSQ) was administered at the beginning of the first 4 cycles.
Results: Of the 508 patients dosed at cycle 1 in the CF arm, and the 521 in the CS
arm, 456 and 498 respectively completed at least one question on the FACT-Ga and
445 and 486 respectively completed at least 37 items. Compliance to questionnaire
fulfillment was more than 80% through Cycle 9. Although there were no overall
difference in FACT-Ga scores between the treatment arms and minimal changes over
time, an advantage for CS relative to CF was observed for Physical Well-Being
(PWB) (51.7% versus 45.1%, p = 0.044). CS treated patients experienced significantly
longer time to worsening in PWB scores, with a median time of 4.5 months (95%
CI: 3.0 – 5.1) compared to 3.0 months (2.8 – 4.6) with CF (p = 0.014).Patients
receiving CS reported higher best and worst score of PWB, Chemotherapy
Convenience and Chemotherapy Concerns scores.
Conclusions: Even if there is little evidence to indicate any difference in FACT-Ga
scores, some advantage to CS relative to CF was observed for PWB, one of the
ix232 | Abstracts Volume 23 | Supplement 9 | September 2012