10 EORTC Abstracts (Posters and Oral Presentations) accepted for the ASCO Meeting
2 – 6 June 2006 Atlanta, Georgia - US

A randomized trial to determine the optimal circadian time of Vinorelbine administration combined with chronomodulated infusion of 5-FU in previously treated pts with metastatic breast cancer (MBC) EORTC study 05971

Abstract No:

 2066

EORTC Group

 Chronotherapy Group

Type of presentation

 POSTER PRESENTATION

Author(s):

 B. Coudert, C. Focan, N. Tubiana, S. Giacchetti, F. Lévi, F. Cvickovic, A. Zambelli, G. Fillet, P. Chollet, M. A. Lentz, S. Marreaud, B. Baron, T. Gorlia

Abstract:

Background: Chronotherapy is an aim to increase efficacy/toxicity ratio.
Objectives: to define the randomized least toxic time (LTT) of V (30 mg/m2/d at D1 and D6), combined with chrono 5-FU (10 pm-10 am) (850 mg/m2 D2-D5) in 3 courses 3 weekly.
Methods: A logistic regression model (LRM) estimated the LTT assuming a sinusoidal distribution over time (i.e. over the 8 different arms) of the toxicity rate observed in each arm. The associated 90% confidence limits (CL) has been obtained by bootstrap method.
Results: 90 patients were recruited. Toxicity in 46 pts led to the V dosage reduction to 25 mg/m2/d. 40 and 43 pts were assigned the V30 and theV25 regimen. 67 pts (81%), 7 (8%), and 9 (11%) received 3, 2 and 1 cycle of chemotherapy respectively. 12% pts went off for toxicity, 5% for PD, 1% for refusal, 1% for unrelated death. 224 cycles were analyzed . V and 5FU relative dose intensities were 79.4% and 78.2% in the V30 pts while 88.1% and 87.4% in the V25 pts. Over the 3 cycles, toxicity by cycle was: Grade (G) 3 and G4 leucopenia in 47% and 29%, G3 and G4 neutropenia in 12% and 77%. G3 febrile neutropenia in 34%. G2 thrombopenia and anemia in 4% each. Other G3 and G 4 toxicity were cardiovascular (2% and 2%), lethargy (4%), diarrhea (4% and 1%), stomatitis (12%), constipation (2% and 4%), other gastrointestinal (5% and 1%), infection (4%), sensory (4%), pulmonary (2% and 3%), alopecia (7%). The LRM
determined a V LTT for tolerability (dose reduction, dose delay or treatment interruption for toxicity reason) around 8H16 [06H04-10H39].
Conclusions: Chronomodulation of V in human can demonstrate a least toxic time of administration at 08H to increase tolerabilty. This time of administration corresponds to the least toxic time and to the most efficient time of administration in animal model (19 HALO). This is the first time that a chronobiological animal pre-clinical data and the logistic regression with bootstrap method statistical design are reinforced by randomized clinical studies in human.
Support Pierre Fabre Oncology, Ligue Bourguignonne contre le Cancer

Preliminary pharmacogenetic evaluation of toxicity data in the prospective multicentre EORTC trial 40015 in metastatic colorectal cancer (CRC).

Abstract No:

3072

EORTC Group

 Gastrointestinal Tract Cancer Group

Type of presentation

 ORAL PRESENTATION

Author(s):

Daniela Aust, Claus-Henning Kohne, Eray Goekkurt, Gerhard Ehninger, Joerg Thomas Hartmann, Eric Van Cutsem, Muriel Debois, Manfred Lutz, Jan Stoehlmacher

Abstract:

 Background: EORTC phase III study 40015 was initiated in 2003 to compare capecitabine (CAP) plus irinotecan (CPT-11) versus 5-FU/LV/irinotecan +/- celecoxib in first line treatment of metastatic CRC. The study was suspended after enrollment of 85 patients due to  8 fatal events not related to disease progression, 4 of which included thrombo-embolic events.
Purpose:  To verify whether functional genetic polymorphisms involved in metabolism of the drugs used are related to an increased risk of toxicity and thrombo-embolic events.
Methods: Seventy-one pts signed informed consent for genetic analyses and material was available for 58 pts. DNA was extracted from normal colonic mucosa or peripheral leukocytes. Polymorphisms were determined using a PCR-based RFLP technique and direct sequencing. Genotypes known to be associated with increased toxicity (diarrhea, mucositis, leucopenia) and thrombo-embolic events were classified as “unfavorable”. Analyses were performed by investigators blinded to the clinical data.
Results: Unfavorable genotypes were distributed equally between CAP+CPT-11 and LV/5-FU+CPT-11 arms. Baseline characteristics and treatment duration were similar in the patients with or without unfavorable genotypes. Unfavorable genotypes of thymidylate synthase (TS-5’; TS-3’) and UDP-glucuronosyltransferase 1A1 (UGT1A1) seem associated with increased grade 3/4 toxicity. 18/35 (51%) pts with unfavorable UGT1A1 genotype experienced toxicity grade 3/4 compared to 3/23 (13%) pts with favorable genotype. 16/36 pts (44%) with unfavorable TS-5’genotype demonstrated toxicity grade 3/4 compared to 5/22 (23%) pts with favorable genotype. Toxicity grade 3/4 was observed in 18/41 (44%) pts with unfavorable TS-3’ genotype and 3/17 (18%) pts with favorable genotype. Increasing grade 3/4 toxicity rates were observed in the pts expressing zero/one (2/18 [11%]), two (7/24 [29%]) or three (12/16 [75%]) unfavorable genotype(s) (p=0.0001). Among the 4 pts who died of a thrombo-embolic event, only one has been analysed at this stage and showed a factor (V) Leiden mutation associated with 10-fold increased risk for thrombo-embolic events. Analyses are ongoing and complete data will be available for presentation.
Conclusion: Our data suggest an association between genetic polymorphisms of TS and UGT1A1 and toxicity. No differences of pharmacogenetic patterns were observed that could explain the increased rate of fatal events in the CAP/CPT-11 arm.

Tumor response to pre-operative chemotherapy (CT) with FOLFOX-4 for resectable colorectal cancer liver metastases (LM). Interim results of EORTC Intergroup randomized phase III study 40983. 

Abstract No:

3500

EORTC Group

 Gastrointestinal Tract Cancer Group

Type of presentation

 ORAL PRESENTATION

Author(s):

T. Gruenberger, H. Sorbye, M. Debois, U. Bethe, J. Primrose, P. Rougier, D. Jaeck, M. Finch-Jones, E.Van Cutsem, B.Nordlinger

Abstract:

 Background: After resection of LM, 5y survival is 30%, but cancer recurrence is frequent. The benefit of combining surgery and CT has not yet formally been proven.
Methods: This study evaluates the value of pre- and postoperative CT in patients with potentially resectable liver metastases from colorectal cancer. Between September 2000 and July 2004, 364 patients were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m² and LV5FU2), 6 cycles before and 6 cycles after surgery (182 patients), and surgery alone (182 patients). The primary endpoint was progression free survival. The purpose of this analysis was to evaluate tumor response to pre-operative treatment and determine if CT induces a tumor size reduction.
Results: Baseline characteristics were similar in both arms: median age: 62.5 yrs, prior adjuvant CT: 41.8%, 1 to 3 metastases: 92.3%, T3 or T4: 80.8%. In the CT arm, 97.7% of the patients were documented to have completed pre-operative CT (81.5% received 6 preoperative cycles). 28.9% of the patients who started pre-operative CT required a dose reduction. Of all patients entered in the trial, 88.3% and 94.9% underwent surgery in the CT and surgery arms, respectively. Resection was achieved in 95.6% of the patients operated  (84.4% of all patients) in the CT arm, and 89.2% of the patients operated (84.7% of all patients) in the surgery arm. As previously reported, preoperative chemotherapy was safely administered. From imaging data (CT scan), median sum of largest diameters of lesions was 45 mm [Q1-Q3:28.0-70.0] (both arms) before treatment and decreased to 30 mm [Q1-Q3: 15.0-55.0] after CT (median relative difference of 29.7%). At pathological examination, median sum of largest diameters of lesions was 34.5 mm [Q1-Q3:20.0-53.0] in the CT arm and 45 mm [Q1-Q3: 29.0-69.0] in the surgery arm.
Conclusions: CT scan measurements were consistent with those performed at pathological examination. Pre-operative CT with 6 cycles of FOLFOX4 resulted in a decrease in diameter of lesions. Since size of metastases at time of surgery is known to have an impact on survival, it is possible that preoperative chemotherapy will improve survival. Survival data should be available at the end of 2006.

A randomized phase III multicenter trial of neoadjuvant docetaxel (Taxotere) plus cisplatin plus 5-fluorouracil (TPF) versus neoadjuvant cisplatin plus 5-fluororuacil (PF) in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN): final analysis of EORTC protocol 24971.

Abstract No:

5516

EORTC Group

 Head & Neck Cancer Group

Type of presentation

POSTER PRESENTATION

Author(s):

E. Remenar, C. van Herpen, J. Germa Lluch, S. Stewart, T Gorlia, M. Degardin, J Bernier, Spirlet C and J.B. Vermorken; EORTC Brussels, Belgium

Abstract:

Background: So far, the Wayne State regimen combining 100 mg/m2 cisplatin on day 1 and 1000 mg/m2/d continuous infusion 5-fluorouracil over 5 days (PF), is the gold standard in advanced SCCHN. Improvement of PF induction chemotherapy by adding a taxane has been suggested from phase II studies and 2 randomized phase III trials. We now report the final analysis of EORTC 24971.
Methods: Eligible were patients (pts) with unresectable stage III/IV SCCHN (no distant metastases), 18 to 70 yrs of age, PS£1, and adequate hematologic, renal and hepatic function. Pts were stratified by primary disease site (oral cavity, oropharynx, hypopharynx, larynx) and treatment center and randomized to PF (as above) or TPF (T 75 mg/m2/1h, P 75 mg/m2/1h, both d1, F 750 mg/m2/d, d1-5) q 3 wks, for 4 cycles unless progression (PD) or unacceptable toxicity, or refusal. Thereafter (interval 4-7 wks), all pts not in PD received radiotherapy (RT: conventional [66-70 Gy], accelerated [max. 70 Gy] / hyperfractionated [max. 74 Gy]). Surgery was allowed before RT (neck) or 3 months after RT (primary, neck). Primary endpoint was progression-free survival (PFS), and 348 pts and 260 events were needed to detect a 50% increase in median PFS (10 vs 15 mo) with 85% power.
Results: Between April 1999 and March 2002, 358 pts were accrued (181 PF, 177 TPF). At a median follow-up (FUP) of 32 mo, PFS was significantly improved with TPF(HR 0.72, p=0.0071; median 8.2 vs 11.0 mo). A 51 mo median FUP showed an overall survival (OS) benefit with TPF (HR 0.71, p=0.0052; median 14.2 vs 18.6 mo). Estimated 3-yr survival rates are 23.9% (95% CI: 17.9%;30.5%) for PF and 36.5% (29.3%;43.6%) for TPF. Response rate also favored TPF (53.6% vs 67.8%, p=0.006). There was more severe (G3+4) leucopenia (41.6% vs 22.9%) and neutropenia (76.9% vs 52.5%) with TPF, and more severe thrombocytopenia with PF (17.9% vs 5.2%). Severe alopecia occured more with TPF (55.5% vs 11.7%); hearing loss (2.8% vs 0%) and toxic death (7.8% vs 3.7%) more with PF.
Conclusions: TPF (® RT) is superior to PF (® RT) for  PFS, OS (including long-term), response rate, and is better tolerated.

Impact on quality of life (QoL) of the addition of docetaxel (T) to neoadjuvant cisplatin plus 5-fluorouracil treatment in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN): EORTC study 24971

Abstract No:

5522

EORTC Group

Head & Neck Cancer Group

Type of presentation

 POSTER PRESENTATION

Author(s):

Bernier J, Remenar E, van Herpen C, Germa Lluch J, Stewart S, Gorlia T, Degardin M, Spirlet C, Vermorken JB

Abstract:

Background: The EORTC 24971 trial compared the efficacy and safety of two neoadjuvant regimens in the treatment of stage III or IV, M0 SCCHN. Eligible patients (pts) with primary tumor sites in the oral cavity, oropharynx, hypopharynx, and larynx and WHO performance status (PS) ≤1) were randomized to 2-4 cycles of cisplatin (P) 100 mg/m² day 1, followed by a continuous infusion of 5-fluorouracil (F) 1000 mg/m²/day from days 1- 5 (PF), or T 75 mg/m² + P 75 mg/m² day
1 then F 750 mg/m²/day from days 1 - 5 (TPF), followed by locoregional radiation therapy (RT). The impact of the two regimens on QoL was a secondary endpoint.
Methods: QoL was assessed at baseline, at cycles 2 and 4, and 6 and 9 months after RT using the EORTC QLQ-C30 questionnaire to obtain the Global Health Status/Quality of Life (GHS/QoL)
score, and the Head and Neck Performance Status Scale (PSS-HN) to assesses the normality of diet, eating in public, and understandability of speech on a scale of 0 to 100. The EORTC QLQ-HN35 questionnaire was also administered at those time-points.
Results: 358 pts were randomized to PF (181 pts) or TPF (177 pts). Baseline (BL) characteristics of the pts were well balanced between groups. TPF was superior to PF in terms of response rate, progression-free survival (primary endpoint), overall survival, and tolerability. Compliance with the QLQ-C30 questionnaire was good ranging from 96% at BL to 41% at 9 months post RT, and was similar between the treatment arms. GHS/QoL scores were comparable at BL between the two arms (p=0.54) and improved in both arms on starting treatment. Over time this score remained stable with TPF, but decreased after RT with PF (treatment-time interaction: p=0.009). Evolution of the PSSH&
N score was better on TPF (normality of diet p= 0.0064; eating in public p=0.0004; understandability of speech p=0.0003). Moreover, TPF was associated  with a 30% reduction in the risk of WHO PS deterioration (p=0.0158)
Conclusions: The use of docetaxel in neoadjuvant treatment of SCCHN improves efficacy without deleterious effects on QoL and functional outcomes.

Does downstaging in patients (pts) with IIIA-N2 non-small cell lung cancer (NSCLC) and a response to induction chemotherapy (ICT) influence outcome with surgery (S) or radiotherapy (RT)? An exploratory analysis of EORTC 08941.

Abstract No:

7047

EORTC Group

 Lung Cancer Group

Type of presentation

 POSTER PRESENTATION

Author(s):

Jan P van Meerbeeck, Gijs Kramer, Catherine Legrand, Alexandre Passioukov, Egbert Smit, Giuseppe Giaccone, Nico van Zandwijk, Paul Van Schil on behalf of the EORTC-Lung Cancer Group (LCG).

Abstract:

 Background: In EORTC 08941, no difference in overall and progression free survival was observed in 332 pts with irresectable stage IIIA-N2 NSCLC, treated with either S or RT after a response to platinum-based ICT (van Meerbeeck, JCO 2005; 23, 1095s). Postoperative radiotherapy (PORT) was given to 40% of pts. In the S-pts, non-randomized exploratory comparisons showed a statistically significant benefit in outcome for (bi-)lobectomy vs. pneumonectomy (p= 0.0088) and for mediastinal lymphnodes (MLN) downstaged vs.non-downstaged pts (p= 0.0009). No difference was observed between S-pts treated with/without PORT. By randomizing after response to ICT, MLN-downstaging is assumed to be equally distributed among both treatment groups but cannot be formally retrieved in RT-pts. In order to compare the influence of MLN-downstaging in each treatment arm, we estimated in an exploratory analysis the outcome in subsets of S-pts and matched paired subsets of RT-pts.
Methods: The subsets of 129 actually resected S-pts are defined as follows: (i) pts with MLN-downstaging at resection, (ii) pts without MLN-downstaging. Each subset was compared to a randomly selected subset of 154 irradiated RT-pts matched on 4 baseline factors: histological subtype, gender, T stage, response to ICT. Kaplan-Meier estimates for overall survival (OS) and logrank p-values were then computed.
Results: A match was feasible for 54/61 downstaged, 59/68 non-downstaged pts. Estimated OS (with 95%CI) for each S-subset and RT-matched pair subset is in the table.

Conclusion: From these exploratory analyses, it appears that: 1. RT improves OS in MLN-non-downstaged pts; 2. S does not improve OS in MLN-downstaged patients. This should however be prospectively assessed.

Results of a longitudinal survey on quality of life (QoL) in 935 patients with supradiaphragmatic early stage Hodgkin lymphoma (HL) enrolled in the EORTC-GELA H8 trial (# 20931)

Abstract No:

 8582

EORTC Group

 Lymphoma Group

Type of presentation

POSTER PRESENTATION

Author(s):

Author Block: N. Heutte, N. Mounier, H. Flechtner, A. M. Mellink, J. H. Meerwaldt, C. Fermé, H. Eghbali, M. Henry-Amar, EORTC Lymphoma Group-GELA; LMNO, Université de Caen Basse-Normandie, Caen, France; Hôpital Saint-Louis, Paris, France; University Hospital, Köln, Germany; University Medical Centre, Utrecht, The Netherlands; Medisch Spectrum Twente, Enschede, The Netherlands; Institut Gustave Roussy, Villejuif, France; Institut Bergonié, Bordeaux, France; Centre François Baclesse, Caen, France

Abstract:

Background: To study the change in posttreatment QoL and fatigue in patients with supradiaphragmatic early stage HL.
Methods: QoL assessment was made using the EORTC QLQ-C30 core questionnaire and fatigue was assessed using the MFI-20 questionnaire. Questionnaires were given immediately after treatment completion and every 6 months thereafter for at least a period of 5 years. Mixed models (Med Decis Making 2003;3:54-66) were used to assess statistically reliable changes of the variables tested with time because they allow unequal number of assessments per patients. Variables tested were the 7 functioning scales and the fatigue scale of the QLQ-C30 questionnaire, the 5 MFI-20 fatigue scales, and time using 6 time periods: 0-6, 7-14, 15-21, 22-32, 33-47, ≥48 months following the end of treatment. The impact of gender, age (<30, 30-49, ≥50 years), treatment (mantle-field irradiation, subtotal nodal irradiation (STNI), 3, 4 or 6 MOPP-ABV and involved-field irradiation or 4 MOPP-ABV and STNI) and treatment-related acute grade 3-4 toxicity was also tested. Patients were censored at relapse when occurred.
Results: Of the 1577 patients enrolled in the trial (1993-1998), 935 (59%, median follow-up 7 years) participated for a total of 3227 assessments. Main clinical characteristics did not differ between patients with missing QoL forms and those with complete data. There were no significant differences in disease-free survival between treatment arms. Significant (P<0.001) improvement with time was observed for all QoL and fatigue variables tested. Overall, young age and male sex significantly (P<0.01) correlated with improvement in all QLQ-C30 dimensions except cognitive functioning. Treatment duration ≥6 months had a significant (P<0.005) negative impact on global QoL. Age≥30 years and treatment duration ≥2 months negatively (P<0.05) influenced MFI-20 variable changes. Previous toxicity and age ≥30 years altered mental fatigue and motivation.
Conclusions: QoL data from the reintegration process of patients into normal life during the first follow-up years show substantial limitations. The impact of treatment is limited. Fatigue remains of great concern in these patients.

Is a stable disease according to RECIST criteria is a real stable disease in GIST patients treated with Imatinib mesylate (IM) included in the intergroup EORTC/ISG/AGITG trial?

Abstract No:

9510

EORTC Group

 Soft Tissue & Bone Sarcoma Group

Type of presentation

 ORAL PRESENTATION

Author(s):

Le Cesne A, Van Glabbeke M, Verweij J, Casali P, Zalcberg J, Reichardt P, Issels R, Judson I, Blay JY

Abstract:

 Background. From 2/2001 to 2/2002, 946 patients (pts) with advanced GIST were randomized to IM at two dose levels within a controlled EORTC/ISG/AGITG trial. This analysis investigates whether achievement of an objective response, according to the RECIST criteria, has any predictive value for time to progression (TTP) and overall survival (OS).
Methods.
According to the protocol, the 3 first disease measurements were foreseen at 2, 4, and 6 months (m). Results of those measurements were classified in 6 categories: PR (>30% reduction of the tumor load), MR (10-30% reduction), NC- (0-10% reduction), NC+ (0-20% increase), PD (> 20% increase or new lesions), and subjective PD (clinical progression, no measurements). Pts included the analyses were those still followed at the measurement point, who had not previously progressed.
Results. A total of 906 pts had measurable disease at entry; from those, 852 were evaluable at 2 m, 681 at 4 m and 642 at 6 m. At all measurement time points, PR and MR resulted in similar TTP and OS; this was also true for NC- and NC+, and for PD and subjective PD. As an example, for the evaluation at 4 m, the median TTP was respectively 2.50, 2.55, 1.86, 1.65, 0.31 and 0.30 years in the 6 groups of pts, while the 3 years OS estimate were 71%, 72%, 57%, 56%, 32% and 0%.
Pts were subsequently classified as responders (more than 10% reduction of the tumor load), no change (less than 10% reduction and less than 20% increase) and PD (> 20% increase, new lesions or clinical PD). This new response category is highly predictive of further progression or survival, for the 2 first measurements points, and in both therapeutic arms, but pts stable at 6 m had the same survival as responders at 6 m. In addition, RECIST response documented at 2, 4 and 6 m resulted in similar TTP and OS.
Conclusions. The RECIST criteria are only optimal for identifying IM-resistant GISTs (PD > 20%) and not adequate for the evaluation of IM efficacy. All pts exhibiting at least a 10% reduction (until complete response) of the tumor load have to be considered as responders to IM (IM-sensitive GISTs). A real stabilisation of the disease consisting in a less than 10% tumor reduction and a less than 20% tumor increase identifies pts who have an intermediate sensitivity to IM.

Gefitinib in second line treatment of metastatic or locally advanced synovial sarcoma expressing HER1: a phase II trial of EORTC Soft Tissue and Bone Sarcoma Group

Abstract No:

9517

EORTC Group

 Soft Tissue & Bone Sarcoma Group

Type of presentation

POSTER PRESENTATION

Author(s):

JY Blay, A. Le Cesne, J. Whelan, A. van Oosterom, I. Ray-Coquard,  I. Judson, PCW Hogendorn, E. Donato di Paola, S. Marreaud, C. Hermans, M. van Glabbeke

Abstract:

Rationale: Synovial sarcomas (SyS) have been reported to over-express HER1 in gene expression profile experiments and immunohistochemistry. On the basis of these observations, gefitinib (IRESSA), an inhibitor of HER1 signalling, was tested in advanced or metastatic SyS failing doxorubicin (Dox) +/- ifosfamide (Ifo).
Patients and methods: This Phase II study was conducted in patients with advanced or metastatic HER1-expressing SyS not amenable to cure with surgery and/or radiation. Patients had measurable progressive lesion(s), pretreatment with up to two lines of single agent therapy with Doxo and Ifo, or one line of a combination in metastatic phase, ECOG performance status 0 to 2, age >=18 years. Gefitinib was  given at the dose of 500mg/day until progression or intolerance.
Primary endpoint was the rate of progression free survival at 3 months (PFS3). A two step Simon design was used with a p0 of 25% and a p1 of 45%, with α and ß of 0.1. 44 patients were scheduled to be recruited.
Results: Between 10/02 and 10/05, 48 patients were included in 12 EORTC STBSG centers. There were 27 (56%) males and 21 (44%) females, with a median age of 42 years (range 19-66). Primary sites of SyS were lower limb, upper limb and thorax (51%, 16% and 13% respectively). Metastatic sites were lung in 92% and soft tissue or lymph nodes in 42%, of the patients. 42%, 40% and 18 % of the patients had received 1, 2 and >2 lines of CT respectively. As of December 2005, 37 patients were evaluable for toxicity and 39 are evaluable for the primary endpoint. Median treatment duration
was 11 weeks (range 2-25).Toxicity (G1-4) reported included fatigue (43%), diarrhea (54%), cough (35%), dyspnea (43%), cutaneous (73%), (or: rash (32%), dry skin (43%), acnea (30%). G3-4 toxicities were dyspnea (9), fatigue (4), cutaneous (2), cough (1), neurological (2), thombosis (2), hypoxia (1), infection (1).There was no drug related death. ]
No dose reductions have been reported so far, but treatment had to be temporarily interrupted in 23% of the patients. As of December 2005, no objective responses were reported. 7 (18%) patients achieved stable disease as best response.
The PFS3 was 13% (5/39 evaluable patients); PFS6 and PFS12 were 10% and 3% respectively.
Conclusion: Disease stabilisation was observed in 18% of patients, but only 13% of SySs expressing HER1 achieved PFS (>=12 weeks) under gefitinib treatment [HER1 gene expression profiling and protein expression were not accurate predictors of gefitinib activity in this study.
IRESSA is a trademark of the AstraZeneca group of companies

The European Organisation For Research And Treatment Of Cancer (Eortc) Translation Procedure For Quality Of Life Questionnaires: Accomplishments And Implications For Clinical Research

Abstract No:

1693

EORTC Group

Quality of Life Group

Type of presentation

Abstract Book Publication

Author(s):

Michael Koller, Center for Clinical Studies, University Hospital
Regensburg, Regensburg, Germany, Neil K. Aaronson, Psychosocial Research
and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands,
Jane Blazeby, Surgery, Bristol Roayl Infirmary, Bristol, United Kingdom,
Andrew Bottomley, Quality of Life Unit, EORTC, Brussels, Belgium, Colin
Johnson, University Surgical Unit, Southampton General Hospital,
Southampton, United Kingdom, Peter Fayers, Public Health, University of
Aberdeen, Aberdeen, United Kingdom, Ramage John, Gastroenterology, North
Hampshire, Basingstoke, United Kingdom, Neil Scott, Public Health,
University of Aberdeen, Aberdeen, United Kingdom, Karen West, Quality of
Life Unit, EORTC, Brussels, Belgium

Abstract:

AIMS: The EORTC Quality of Life (QoL) questionnaires are used in
international trials and standardized translation procedures are
therefore required. This report summarizes the EORTC translation
procedure, its accomplishments and problems. METHODS:  Translations
follow a forward-backward procedure, independently carried out by two
native-speakers of the target language. Discrepancies are arbitrated by
a third consultant, and solutions are reached by consensus. Translated
questionnaires undergo pilot-testing. Suggestions are incorporated into
the final questionnaire version. Requests for translations come from the
module development groups or pharmaceutical industry, and most
translations are performed by professional translators. The translation
procedure is managed and supervised by the Translation Committee within
the EORTC QoL Group. RESULTS: To date, the EORTC QLQ-C30, has been
translated and validated into 72 languages, with a further 6
translations in progress. Condition-specific modules have been
translated in up to 70 languages. Translations include all major
Western, and many African and Asian languages. The following major
translation problems were encountered: lack of expressions for specific
symptoms in various languages, the use of old-fashioned language, recent
spelling reforms in several European countries, and different weights of
social issues between Western and Eastern cultures. The EORTC
measurement system is now registered for use in over 9000 clinical
studies in 80 countries worldwide CONCLUSIONS: The EORTC provides a
strong infrastructure and methodology to produce high quality
translations of their QoL questionnaires. Translation problems have been
identified. The EORTC Quality of Life Group is using a unique
cross-cultural database of over 38,000 questionnaire responses to help
shed light on whether observed problems are due to
procedural/methodological shortcomings or subtle cross-cultural
differences in concepts of health, illness and QoL.

Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015.

Abstract No:

3072

EORTC Group

Gastrointestinal Tract Cancer Group

Type of presentation

POSTER PRESENTATION

Author(s):

J. De Grève, C.H. Köhne, J. Hartman, I. Lang, P. Vergauwe, K. Becker, D. Braumann, M. Debois, U. Bethe, E. Van Cutsem.

Abstract:

Background: Oral fluoropyrimidines in combination with irinotecan may be an alternative to infusional 5-FU/FA+irinotecan. Cox-2 inhibitors may enhance the antineoplastic activity of chemotherapy (CT).
Methods: Patients with ECOG PS<2, age>18 and measurable disease were randomised in a 2x2 factorial design to FOLFIRI (Douillard’s regimen) or capecitabine 2x1g/m² d1-14 plus irinotecan 250mg/m² d1, qd22 (CAPIRI), and to daily celecoxib 2x400mg (C) or placebo (P). 692 patients were planned to compare PFS as primary endpoint. The trial was suspended after 85 pts (44 CAPIRI and 41 FOLFIRI) due to the occurrence of 8 fatal events unrelated to disease progression (Köhne, ASCO 2005, A3525).
Results: Baseline characteristics were well balanced. Three pts did not start treatment. Of the pts who started CT, 53% (23/43) in the CAPIRI and 33% (13/39) in the FOLFIRI arms required a dose reduction. Grade ≥3 diarrhoea occurred in 37% (16/43) and 13 % (4/39) on CAPIRI and FOLFIRI, respectively. Median number of CT cycles: 3 (CAPIRI) and 5 (FOLFIRI). Median dose intensity for irinotecan: 83% (CAPIRI) and 85% (FOLFIRI). Response rate (RR): 5/23 (22%) in CAPIRI+C, 10/21 (48%) in CAPIRI+P, 6/19 (32%) in FOLFIRI+C and 10/22 (45%) in FOLFIRI+C. RR for CAPIRI vs FOLFIRI: 15/44 (34%) versus 16/41 (39%), RR for Celecoxib vs Placebo: 11/42 (26%) vs. 20/43 (46 %). Median PFS: 5.9 months (95% CI: 4.4-8.9) with CAPIRI vs 9.6 months (95% CI: 6.9-11.8) with FOLFIRI (HR=1.31, 95%CI: 0.8-2.1), and 6.9 months (95% CI: 5.5-10.4) with C vs 7.8 months (95% CI: 6.0-12.0) with P (HR=1.1, 95%CI: 0.7-1.8). Median OS: 14.8 months (95% CI: 10.7-18.3) with CAPIRI vs 19.9 months (95% CI: 18.9-n.a.) with FOLFIRI (HR=3.2, 95%CI: 1.4-7.3), and 18.3 months (95% CI: 10.2-n.a.) with C versus 19.9 months (95% CI: 16.7-n.a.) with P (HR=1.25, 95%CI: 0.6-2.6).
Conclusions:  The data suggest that celecoxib might reduce response to CT and this warrants further preclinical investigation. The stratified analysis failed to demonstrate the non-inferiority of CAPIRI as compared to FOLFIRI. Small sample size and confounding safety issues prevent us from drawing definitive conclusions. Results of larger studies would be needed.