A.N.M. Wymenga

Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin–gemcitabine or carboplatin–paclitaxel: NVALT-3 a phase III study

BACKGROUNDnElderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks.nnnPATIENTS AND METHODSnA total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival.nnnRESULTSnThere were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors.nnnCONCLUSIONSnPaclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.

Two sides of the medallion: poor treatment tolerance but better survival by standard chemotherapy in elderly patients with advanced-stage diffuse large B-cell lymphoma

BACKGROUNDnWe investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival.nnnPATIENTS AND METHODSnData from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009.nnnRESULTSnOnly 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index.nnnCONCLUSIONSnStandard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.BACKGROUNDnWe investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival.nnnPATIENTS AND METHODSnData from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009.nnnRESULTSnOnly 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index.nnnCONCLUSIONSnStandard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.

A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG

BACKGROUNDnProspective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial.nnnPATIENTS AND METHODSnPatients were randomized to six cycles of PLD (45 mg/m2 every 4 weeks) or eight cycles of capecitabine (1000 mg/m2 twice daily, day 1-14 every 3 weeks).nnnRESULTSnThe study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively.nnnCONCLUSIONnBoth PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully.nnnCLINICAL TRIAL NUMBERSnEudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.BACKGROUNDnProspective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial.nnnPATIENTS AND METHODSnPatients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks).nnnRESULTSnThe study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively.nnnCONCLUSIONnBoth PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully.nnnCLINICAL TRIAL NUMBERSnEudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.

A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study

BACKGROUNDnIn ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer.nnnPATIENTS AND METHODSnIn a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS).nnnRESULTSn151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients.nnnCONCLUSIONnCelecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.BACKGROUNDnIn ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer.nnnPATIENTS AND METHODSnIn a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS).nnnRESULTSn151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients.nnnCONCLUSIONnCelecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands

BACKGROUNDnWe determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival.nnnPATIENTS AND METHODSnData from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997-2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed.nnnRESULTSnThe proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997-2000 to 23% in 2007-2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997-2000 to 35% in 2004-2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4-0.5).nnnCONCLUSIONnThere has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.BACKGROUNDnWe determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival.nnnPATIENTS AND METHODSnData from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997-2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed.nnnRESULTSnThe proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997-2000 to 23% in 2007-2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997-2000 to 35% in 2004-2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4-0.5).nnnCONCLUSIONnThere has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.

1433PBURDEN AND DISTRESS OF CAREGIVERS OF PATIENTS (PTS) ON TYROSINE KINASE INHIBITORS (TKI) FOR GASTROINTESTINAL STROMAL TUMORS (GIST): A CROSS-SECTIONAL STUDY

S.M.C.H. Langenberg,,1, A.N.M. Wymenga2, A.K.L. Reyners3, C. van Herpen1, J.B. Prins4, W.T.A. van der Graaf5 Medical Oncology, Radboud University Medical Center, Nijmegen, NETHERLANDS Medical Oncology, Medisch Spectrum Twente (MST), Enschede, NETHERLANDS Department of Medical Oncology, University Medical Center Groningen, Groningen, NETHERLANDS Medical Psychology, Radboud University Medical Center, Nijmegen, NETHERLANDS Medical Oncology /452, Radboud UMC, Nijmegen, NETHERLANDS

1345PCAREGIVERS’ BURDEN AND FATIGUE DURING PATIENTS’ (PTS) TREATMENT WITH CURATIVE, CONCOMITANT CHEMORADIOTHERAPY (CRT) FOR LOCALLY ADVANCED HEAD AND NECK CANCER (LAHNC): A PROSPECTIVE, OBSERVATIONAL STUDY

ABSTRACT Aim: Caregivers are of vital importance supporting LAHNC pts during CRT. Since symptoms of pts with LAHNC are very visible and treatment is burdensome, this may impact caregivers as well. We therefore aimed to explore the course of caregivers’ burden and fatigue in relation to pts’ fatigue during and after CRT. Methods: Caregivers and pts completed a general questionnaire and the subscale fatigue severity of the Checklist Individual Strength (healthy controls M 17.3, SD 10.1). Additionally, caregivers completed the Self-Perceived Pressure from Informal Care questionnaire measuring burden (caregivers palliative phase M 6.0, SD 2.2). The severity of burden and fatigue was determined with validated cut-off scores. Measurements were conducted prior to CRT (T0), 1 week (T1) and 3 months after completing CRT (T2). The course of fatigue and burden was analyzed with general linear models. Results: 60 couples were included. 93% completed T0, 82% T1 and 75% T2. Caregivers’ and pts’ mean age was 54 (SD 14) and 56 years (SD 10), 75% and 34% were female, respectively. 70% of the caregivers were pts’ partner. At T0, caregivers’ burden was moderate (M 4.1, SD 2.4), as was burden at T1 (M 4.6, SD 2.4). At T2, a significant decrease in burden was observed (M 3.2, SD 2.4; p = .001). For caregivers’ fatigue, normal levels were found at T0 (M 24.3, SD 13), rising to moderate levels at T1 (M 27.5, SD 12.4), with a significant decrease to normal at T2 (M 22.4, SD 11.8; p = .019). Caregivers’ fatigue and burden were correlated at all time points (r = 0.43-0.54, p = .001). Comparing caregivers’ fatigue to pts’ fatigue over time, a peak in fatigue at T1 was found for both groups (p = .001). Pts were more fatigued over time (p = .025), with a lower level at baseline but a faster increase in fatigue than their caregivers (p = .003). Additionally, pts’ fatigue showed higher levels at T2 compared to T0 (p = .026). Conclusions: During and after LAHNC pts’ treatment, and regarding their severity of fatigue, caregivers seem resilient. When proactive support is considered for caregivers at risk for overstraining, intervention early during CRT is recommended. Disclosure: C. van Herpen: Dr. C.M.L. van Herpen received research funding from Novartis and Merck, and serves on a Merck advisory board W.T.A. van der Graaf: Prof. dr. W.T.A. van der Graaf received research funding from Novartis. All other authors have declared no conflicts of interest.