Line Palliative Chemotherapy Research Articles

Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer.

To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship.

Abstract 4076: Combination of docetaxel with sulforaphane synergistically inhibits triple negative breast cancer and cancer stem cells

Abstract Triple negative breast cancer (TNBC) (ER-, PR-, Her2-), constituting 10-20% of all breast cancers, is a heterogeneous disease with limited treatment options and poor prognosis. TNBCs exhibit rapid progression with the duration of response to first line palliative chemotherapy typically less than 12 weeks, and overall five year survival of patients with metastatic TNBC of 22%. The cancer stem cell (CSC) model provides an attractive explanation for relapse of TNBC after primary therapy since these cells demonstrate resistance to conventional chemotherapy. CSCs which survive primary treatments, such as docetaxel, may self-renew and differentiate into the heterogeneous tumor bulk resulting in local recurrence and distant metastasis. Docetaxel has been demonstrated to not only fail to eliminate CSCs but expands this population in preclinical models. Further, docetaxel increases circulating IL-6 in patients following therapy, a cytokine reported to expand breast CSCs. Therefore, we sought to combine docetaxel with a small molecule CSC inhibitor capable of reducing IL-6 production (sulforaphane, SF) for the effective treatment of TNBCs. Our results in vitro demonstrate that docetaxel treatment (5 nM) increases the proportion of CSCs in TNBC cell lines (SUM149 and SUM159) as evident by flow cytometry analysis using the ALDEFLUOR assay (70.6±22.0%) and cells which are CD44+/CD24-/EpCAM+ (2.9 fold). Mammosphere formation assay reveals 1 nM docetaxel increases secondary sphere formation rate by 75.8±29%. As determined by ELISA, 5 nM docetaxel treatment for 72 hours induces 3.5 fold increase in IL-6 production. Conversely, SF (2.5 μM) selectively reduces the proportion of ALDEFLUOR positive cells (51.5±15.0%) and mammosphere formation (39.2±3.8%) while reducing IL-6 (55.6±5.0%) through regulation of NF-kB activity. In combination docetaxel and SF synergize to effectively reduce bulk cell line proliferation (combination index range 1-0.093). Further, SF prevents docetaxel mediated CSC expansion and IL-6 production. Using a mouse xenograft model docetaxel (10 mg/kg weekly) reduces tumor growth of established tumors by 83.2±6.0% whereas SF (50 mg/kg daily) inhibits primary tumor growth by 37.4±14.6%. In addition, secondary reimplantation assays with limiting dilution analysis reveals docetaxel increases the frequency of the tumor initiating CSCs (1/1514 control cells vs 1/330 docetaxel treated cells) while SF reduces the frequency to 1/3181 cells. In vivo, the combination of docetaxel and SF exhibits a greater reduction in primary tumor volume (92.5±2.1% reduction relative to control), and synergistically inhibit the CSC population (1 in 4245 cells). These results suggest that SF mediated inhibition of breast CSCs and IL-6 provide a scientific rationale for using this agent in combination with docetaxel for TNBC. Citation Format: Joseph P. Burnett, Ronack B. Shah, Hayley J. Paholak, Sean P. McDermott, Yasuhiro Tsume, Max W. Wicha, Duxin Sun. Combination of docetaxel with sulforaphane synergistically inhibits triple negative breast cancer and cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4076. doi:10.1158/1538-7445.AM2015-4076

Quality of life across chemotherapy lines in patients with advanced colorectal cancer: a prospective single-center observational study.

Palliative chemotherapy in patients with nonresectable advanced colorectal carcinoma is performed to prolong survival, alleviate tumor-associated symptoms, and maintain or improve health-related quality of life (HRQOL). In this prospective single-center observational study, we assessed HRQOL across the various lines of palliative chemotherapy. HRQOL data were acquired using the EORTC Quality of Life Questionnaire-C30 (QLQ-C30) questionnaire. The first assessment was performed at the beginning of each chemotherapy line, the second after three cycles, and the third at the end of chemotherapy. Further assessments were conducted during checkups every 3 months in our outpatient unit. In total, 100 consecutive patients with colorectal carcinoma (mean age 66.4 years; 60 % men) treated with palliative chemotherapy were recruited. Generally, QOL deteriorated constantly across time. Physical functioning, fatigue, pain, dyspnea, and appetite worsened steadily from first-line chemotherapy to the later treatment phase. Global QOL, emotional functioning, and role functioning improved slightly after the end of first-line chemotherapy, deteriorated during second-line chemotherapy to the level of first-line chemotherapy, and further deteriorated in the later treatment phases. In additional analyses, we found the largest differences between patients with and without a treatment response for pain (19.0 vs. 37.2 points) and appetite loss (17.4 vs. 32.7 points). The individual QOL domains deteriorated constantly across time. Our data indicate that patients undergoing first- and second-line palliative chemotherapy experience stabilization of global QOL and psychosocial symptoms. We also found that unselected patients who achieved a treatment response had a lower symptom burden and better QOL than did patients with progressive disease.

First line palliative chemotherapy in elderly patients with advanced soft tissue sarcoma.

BackgroundThe efficacy and toxicity of first line palliative chemotherapy for soft tissue sarcomas (STS) in the elderly is poorly described.MethodsPatients over the age of 65 years receiving first line chemotherapy for advanced non-GIST STS January 1998 - January 2012 at the Royal Marsden Hospital were identified. Data regarding survival and predictive factors were collected retrospectively.Results120 patients (52 females) with a median age of 72 (range 65–83) were treated. The most common histological subtypes were undifferentiated sarcoma (30%), leiomyosarcoma (27%), angiosarcoma (14%). 42% of patients had high grade tumours. 70% of patients had metastatic disease at presentation; lung metastasis being the most common disease site (72%). 80% received single agent chemotherapy, mostly with doxorubicin (60%). The median number of cycles was 2 (IQR 3). A partial response was reported in 20% of patients with disease stabilisation in a further 20%. 38% of patients were hospitalised for chemotherapy related toxicity. The median overall survival (OS) was 6.5 months (95% CI 4.7-8.3). Anaemia, lymphopenia, hypoalbuminemia, sarcoma subtype and co-morbidities were predictive for overall survival.ConclusionThe overall survival for elderly patients with STS is poor but several predictive factors have been identified. Hospital admissions for chemotherapy related toxicity are common.

Risk of treatment related death and febrile neutropaenia with first line palliative chemotherapy for de novo metastatic breast cancer in clinical practice in a middle resource country.

The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test. Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319). In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Sustained response with gemcitabine plus Nab-paclitaxel after folfirinox failure in metastatic pancreatic cancer: Report of an effective new strategy

Folfirinox has shown a benefit in terms of survival and quality of life in first line treatment of metastatic pancreatic cancer. However, efficacy of second line chemotherapy after folfirinox is still limited. Gemcitabine plus Nab-paclitaxel have been recently validated as first line treatment with an increased overall survival compared to gemcitabine. This combination has never been studied as second-line after folfirinox. A metastatic pancreatic cancer was diagnosed in a 60-year-old patient with a performance status of 0. After 10 cycles of folfirinox, and an initial objective response, we objectively noted progressive disease according to the RECIST 1.1 criteria together with an increased carbohydrate antigen 19-9. The multidisciplinary team decided to use gemcitabine plus Nab-paclitaxel as second line palliative chemotherapy. After 2 months, we obtained an objective response. After 6 months, this response was maintained with an acceptable tolerability. Gemcitabine plus Nab-paclitaxel, as second line palliative chemotherapy, after failure of folfirinox, could be a good strategy for patients with a performance status of 0 and 1. Obviously, this data has to be confirmed in larger patients series and in future comparative clinical studies.

Comparison of outcomes for the elderly patients treated with single agent versus doublet regimen as first-line chemotherapy for recurrent or metastatic gastric cancer.

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.

Colorectal high-grade neuroendocrine carcinoma: A single institution experience.

540 Background: Colorectal high-grade neuroendocrine carcinoma (HGNEC) is a rare and aggressive disease that lacks standard management recommendations. Methods: The records of all patients with colorectal HGNEC diagnosed at MD Anderson Cancer Center between 1991 and 2013 were retrospectively reviewed for clinicopathological features and clinical outcomes. Results: One hundred patients with histologically confirmed colorectal HGNEC were identified. Median age at diagnosis was 55 years with 51 males. Family history of cancer was present in 59% (first degree) of patients and a tobacco smoking history in 54%. Most frequent symptoms at diagnosis were: abdominal or rectal pain (52%), rectal bleeding (49%) and change in bowel habit (52%). Small cell carcinoma was the most common histology (89%), with large cell neuroendocrine carcinoma in 8% and mixed histology 2%. The expression of chromogranin, synaptophysin and neuron specific enolase was positive in 58%, 93% and 87%, respectively. In our institution, 40% of HGNECs arise in the rectum, compared to 25% of adenocarcinomas (P&lt;0.001 for comparison). Sixty four patients (64%) presented with metastatic disease at diagnosis. Median overall survival (OS) was 11.8 months, with 19.3 versus 8 months for localized and metastatic disease, respectively (p&lt;0.01). Two and five year OS was 23% and 8%, respectively. Cecal primaries had a higher rates of metastatic disease at presentation (OR=5, P=0.026), but stage-specific outcomes did not differ by tumor location. Treatment with a platinum-based chemotherapy (CT) was used in 63 (81%) patients in first line palliative CT and the objective response rate was 43%. For localized disease, neoadjuvant treatment was used in 36% of patients and adjuvant therapy in 47% and was associated with a trend toward improved survival (median OS 20.4 versus 15.4 months, P=0.08). Conclusions: Colorectal HGNEC has an aggressive biology with rectum being the most common site and cecum the site most associated with distant metastases at diagnosis. For localized disease early diagnosis and multimodality approach are important for better outcomes while systemic CT appears to be the mainstay of treatment for advanced disease.

Quality of life during chemotherapy in lung cancer patients: results across different treatment lines

Background:Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients' quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy.Methods:Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis.Results:One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL.Conclusion:The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies.

Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma.

e17033 Background: After the failure of first-line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care second-line treatment that is proven to improve quality of life or prolong survival. Both methotrexate and cetuximab has shown a single-agent activity in advanced HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. After failing at least one line of palliative chemotherapy, patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 400 mg/m2 loading dose at week one followed by 250 mg/m2 maintenance dose weekly. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included in the study. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 34 patients were included in the study, 26 male and 8 female, 18 African American and 16 Caucasian. Median patient age was 60 years old. 18, 6 and 6 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as first line because there were not candidates for more aggressive chemotherapeutic regimens. The average received number of weekly treatments was 25 (8-69) and average number of cycles was 6 (2-17). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. Median progression free survival was 4.9 months and overall survival was 10.7 months. Overall survival based on race was 9.9 months for Caucasians and 10.7 months for African Americans (P=0.0391). Grade I and II skin rash was observed in 41% of patients, no grade III/IV toxicities were noticed. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.

Neutrophil/lymphocyte ratio (NLR) as a prognostic factor in biliary tract cancer (BTC).

4130 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Risk factors include conditions associated with chronic inflammation. NLR, an inflammatory marker, is prognostic in several cancers but has not been reviewed in large BTC series, hilar or GBC. Methods: Baseline demographics and NLR at diagnosis were evaluated in 864 patients (pts) with BTC from 01/87 - 12/12 treated at Princess Margaret Cancer Center. Their prognostic significance for overall survival (OS) was determined using a Cox proportional hazards model. Results: High NLR ≥3.0 was associated with poor survival using univariable analysis as was stage/site of primary (P&lt;0.05), age &gt;65yrs, lymphocytes ≤1.6 (P&lt;0.01), neutrophils ≥5.0, platelets ≥280, hemoglobin (Hb) &lt; 110 g/L (P&lt;0.001). Median OS in pts with NLR&lt;3.0 was 21.6 mo, 12.0 mo with NLR ≥3.0 (P&lt;0.001). NLR retained its significance as a prognostic marker on multivariable analysis (Table), along with GBC (P&lt;0.05), age&gt;65yrs, DBD primary (P&lt;0.01), stage and Hb &lt;110g/L (P&lt;0.001). NLR was prognostic for OS on multivariable analysis for hilar: overall (Table) and advanced grp (n=102) (HR 1.68, 95%CI 1.07-2.64, P&lt;0.05) and in advanced DBD (n=102) (HR 1.63, 95%CI 1.03-2.57,P&lt;0.05). On subgrp analysis, NLR was prognostic for OS in advanced BTC (ABTC) (n=538) (P&lt;0.01) but not in surgical grp. NLR did not predict RECIST response to first line palliative chemotherapy in ABTC. Conclusions: Baseline NLR is prognostic in BTC, specifically ABTC and hilar subgrp, suggesting the importance of systemic inflammation influencing outcome in pts with ABTC, thus providing a simple inexpensive prognostic biomarker while also possibly identifying pts that may benefit from antiinflammatory mediation. NLR was not predictive for response in BTC. [Table: see text]

Outcome of patients treated with palliative weekly Paclitaxel plus Cetuximab in recurrent head and neck cancer after failure of platinum-based therapy

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.

Unresectable Metastatic Colorectal Cancer Treatment and Survival – Pauls Stradins Clinical University Hospital Experience

SummaryIntroduction.Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include oxaliplatinand irinotecan-based first-line regimens and the increasing use of targeted monoclonal antibodies, survival rates for patients with mCRC remain unacceptably low.Aim of the Study.Is to analyze survival in patients with unresectable metastatic colorectal cancer.Materials and Methods.Retrospective study of unresectable metastatic colorectal cancer patients who underwent palliative chemotherapy in Clinic of Oncology of PaulsStradins Clinical University Hospital from 2004 to 2011was done.Results.102 patients had a median PFS of 8 months and median OS of 16 months. Subgroup analysis revealed median PFS of 9 months in the synchronous metastatic disease group and 7 months in the metachronous metastatic disease group (p=0.0089) and median OS of 16 months and 12 months, respectively (p=0.0168).Median OS was 11 months in patients received only one line palliative chemotherapy compared to 19 months in patients received more than one line therapy (p&lt;0.0001).Conclusions.The parameter of synchronous and metachronous metastases is of prognostic value in mCRC patients.Second line palliative chemotherapy prolongs overall survival in patient with mCRC.

1498P - A Prognostic Score to Guide Appropriate Delivery of First Line Palliative Chemotherapy for Advanced Soft Tissue Sarcoma

ABSTRACT Objective The study investigated predictive variables of overall survival (OS) in patients treated with first line palliative chemotherapy for locally advanced/ metastatic soft tissue sarcoma (STS) from 1998-2008. Poor performance status (PS) has been identified as a powerful risk factor for early death in this population. Establishing additional objective variables may further aid decision making when considering the risk/benefit ratio of systemic chemotherapy. Methods Pre-treatment demographic, STS-specific and biochemical variables of 501 patients were reviewed retrospectively. Patients with chemo-sensitive subtypes gastro-intestinal stromal tumour, rhabdomyosarcoma, desmoplatic small round cell tumour were excluded. Significant prognostic factors in univariate analysis were further evaluated using multivariate analysis (Cox regression). Results Median OS was 11.4 months, 90-day mortality 17% and the 1, 2 and 5 year survival was 43, 23 and 2% respectively. The Cox model identified age >60 years [Hazard ratio: 1.35 (95% confidence interval 1.01-1.80) p = 0.04], >2 sites of metastases [HR: 1.47 (1.14- 1.90) p =0.003], presence of soft tissue metastases [HR 1.23 (0.99 -1.51) p= 0.054] together with lymphocytes Conclusion Alongside PS, we propose a simple objective STS-specific score as a further aid to clinical decision making. Patients with a median prognosis of 3 months are unlikely to derive significant benefit from chemotherapy and this needs to be discussed with the patient. This score now needs to be validated prospectively in an independent cohort. Disclosure All authors have declared no conflicts of interest.

Chemotherapy in patients with advanced pancreatic cancer: too close to death?

We evaluated the attitude in using chemotherapy near the end of life in advanced pancreatic adenocarcinoma (PAC). Clinical and laboratory parameters recorded at last chemotherapy administration were analyzed, in order to identify risk factors for imminent death. Retrospective analysis of patients who underwent at least one line of palliative chemotherapy was made. Data concerning chemotherapy (regimens, lines, and date of last administration) were collected. Clinical and laboratory factors recorded at last chemotherapy administration were: performance status, presence of ascites, hemoglobin, white blood cell (WBC), platelets, total bilirubin, albumin, LDH, C-reactive protein (C-rp), and Ca 19.9. We analyzed 231 patients: males/females, 53/47 %; metastatic/locally advanced disease, 80/20 %; and median age, 66 years (range 32-85). All patients died due to disease progression. Median overall survival was 6.1 months (95 % CI 5.1-7.2). At the last chemotherapy delivery, performance status was 0-1 in 37 % and 2 in 63 %. Fifty-nine percent of patients received one chemotherapy line, while 32, 8, and 1 % had second-, third-, and fourth line, respectively. The interval between last chemotherapy administration and death was <4 weeks in 24 %, ≥4-12 in 47 %, and >12 in 29 %. Median survival from last chemotherapy to death was 7.5 weeks (95 % CI 6.7-8.4). In a univariate analysis, ascites, elevated WBC, bilirubin, LDH, C-rp and Ca 19.9, and reduced albumin were found to predict shorter survival; however, none of them remained significant in a multivariate analysis. A significant proportion of patients with advanced PAC received chemotherapy within the last month of life. The clinical and laboratory parameters recorded at last chemotherapy delivery did not predict shorter survival.

P-0224 Addition of Cetuximab to Oxaliplatin-Based Chemotherapy on Liver and Spleen Size and Thrombocytopenia in Patients with Metastatic Colorectal Cancer

ABSTRACT Introduction A previous retrospective study revealed that oxaliplatin could induce splenic enlargement which in turn was associated with thrombocytopenia in patients with early stage colorectal cancer. However it has not still been known whether cetuximab aggravates or alleviates such effects in patients with metastatic colorectal cancer. We performed a retrospective study to investigate the effect of addition of cetuximab to oxaliplatin-based regimen as 1st line palliative chemotherapy on liver and spleen size and its association with thrombocytopenia in patients with metastatic colorectal cancer. Methods Ninety two consecutive patients with metastatic colorectal cancer, recruited from January 2008 to December 2011, received either oxaliplatin-based chemotherapy (XELOX or FOLFOX4, n=57) and the same regimen with cetuximab (n=35) as 1st line palliative chemotherapy for their metastatic colorectal cancer. Contrast-enhanced computed tomography (CT) scan was performed at baseline and after chemotherapy +/- cetuximab at regular intervals. The volumes of the residual liver after excluding liver metastases if present and spleen at baseline and after oxaliplatin-based chemotherapy +/- cetuximab were determined by contouring these organs in Eclipse Treatment Planning System version 8.9. Changes in volume of liver and spleen in all patients and subgroups stratified according to the use of cetuximab were compared by paired and independent sampled t-tests respectively. Binary logistic regression was performed for any factors predictive of thrombocytopenia defined as Results Both liver (mean increase 4.2%, p=0.029) and spleen (mean increase 36.4%, p=0.000) enlarged in all patients after the use of oxaliplatin-based chemotherapy +/- cetuximab. Use of cetuximab in addition to oxaliplatin did not aggravate or protect the liver (mean decrease 0.56% for chemotherapy alone group vs mean increase 4.71% for cetuximab group, p=0.374) or spleen (mean increase 41.0% for chemotherapy alone group vs mean increase 31.9% for cetuximab group, p=0.338) from further change in size. Cumulative dose of cetuximab correlated with platelet count (Pearson's correlation coefficient r=0.503, p=0.020) and it was also associated with thrombocytopenia (relative risk: 4.563, p=0.033). However the risk of grade 3 or above (CTCAE version 4.0) thrombocytopenia was similar between those who received cetuximab and those who did not. Conclusion Oxaliplatin-based chemotherapy was confirmed to increase liver and spleen size in patients with metastatic colorectal cancer. Addition of cetuximab to oxaliplatin-based chemotherapy did not cause further hepatic or splenic enlargement but was associated with an increased chance of mild degree of thrombocytopenia.

Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma: A retrospective study.

e16019 Background: After the failure of first line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care treatment that improves survival or quality of life. Both, methotrexate and cetuximab have single agent activity in metastatic HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. Patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 250 mg/m2. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 39 patients were included, 27 male and 12 female. Median patients’ age was 57 years old. 35 patients received methotrexate plus cetuximab (MC) after failure of prior line of palliative chemotherapy. 17, 10 and 8 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as 1st line because they were not candidate for more aggressive therapy. The average received number of weekly treatments was 31 (8-95) and average number of cycles was 7 (2-23). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. 13 patients received prior cetuximab as single agent or in combination. Median progression free survival was 7.1 months and overall survival was 9.8 months. Considering the line of therapy, the median survival was 6.9, 10.1, 13.5 and 9.9 months for patients received MC as 1st, 2nd , 3rd and 4th line of therapy respectively (P= 0.356). Grade 1 and 2 skin rash and hypomagnesimia were observed in 47% and 36% of patients. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective well designed studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.

Clinical and biologic factors associated with time to progression in patients treated by first-line palliative FOLFOX chemotherapy in metastatic colorectal cancer.

e14159 Background: Chemotherapy is the mainstay of treatment patients with metastatic colorectal cancer. The choice of first-line treatment is difficult, especially when cost-effectiveness is the primary constraint. Thus, the optimal use of the clinical and biological factors influencing prognosis would be beneficial. The aim of our study was to identify factors affecting the time to progression (TTP) after first-line FOLFOX chemotherapy in palliative setting. Methods: The study is a retrospective analysis of the series of consecutive patients from large cancer center in south of Poland. The analysis was carried out in the group of 180 patients (37.2% of women), treated between 2007-2010 by FOLFOX-4 regimen and followed-up with the median time of observation 16.3 month. Patients received chemotherapy with median time of 5.0 months, median 10 cycles. Progression was defined as PD by RECIST criteria, death due to disease or sympomatic deterioration. 94 paraffin blocks were available for KRAS testing and gene expression analysis by real-time PCR. Results: The median TTP (counted from beginning of chemotherapy) was 8.6 month, the median TTP from the end of treatment was 3.4 month. We tested the wide range of clinical variables associated with both disease and and patient status by multivariate Cox regression analysis. Two most potent independent negative predictors were identified: the presence of massive lymph node involvement as assessed in CT scan before palliative treatment (&gt;10 nodes enlarged) – hazard ratio 2.82, p&lt;0.001; and tumor grade in histopathological assessment (grade 3 vs. grade 1-2) – hazard ratio 2.76, p=0.003. KRAS status was not prognostic for the TTP; Ki67 gene expression measurement by quantitative RT-PCR did not predict better that the routine assessment of grade. Patients with either grade 3 or lymph node involvement showed significantly shorter TTP (median 5.7 months vs 9.7 months in patients with none of these factors). Conclusions: High tumor grade and the massive involvement of lymph nodes worsen prognosis and shorten time to progression in patients treated with first line palliative FOLFOX chemotherapy.

The first two lines of chemotherapy for anthracycline-naïve metastatic breast cancer: A comparative study of efficacy between anthracyclines and nonanthracyclines.

1061 Background: For anthracycline-naïve metastatic breast cancer (AN-MBC) patients, past evidence indicated that anthracyclines are beneficial in the first-two lines of palliative chemotherapy but with considerable toxicities. However, with the provision of newer chemotherapies, comparative studies addressing the efficacy between anthracyclines and non-anthracyclines in the first-two lines of palliative chemotherapy for AN-MBC were lacking. Methods: We collectedclinicopathological characteristics of AN-MBC patients who had received palliative chemotherapy in National Taiwan University Hospital between 2001 and 2006. Patients were classified as anthracycline or non-anthracycline group according to the first-two lines of chemotherapy. Kaplan-Meier method and log-rank test were used for the estimation and comparison of both overall survival (OS) and time to treatment failure of the first-two lines (TTF2).Cox proportional hazard model was used for OS and TTF2. Best composite response rate (BCRR) were compared with logistic regression test. Results: A total of 109 (43.1%) patients in the anthracycline group and 144 (56.9%) patients in non-anthracycline group were analyzed. Between these two groups, the distributions of clinicopathological variables were generally similar and their median OS (33.3 vs 34.2 months, p = 0.179), TTF2 (13.3 vs 12.7 months, p = 0.104), and BCRR (59.5 vs 61.1%, p = 0.81) were not significantly different. Subgroup analysis showed that patients in the anthracycline group had a trend toward better OS in the estrogen receptor (ER) negative/ human epidermal growth factor receptor type II (HER2) positive subtype (median OS 58.0 vs 31.2 months, p = 0.081). In multivariate analysis, patients in the anthracycline group had a trend toward better OS (HR 0.72, 95% CI 0.52 - 1.00, p = 0.052). However, the exclusion of ER-/Her2+ subtype attenuated the impact of early anthracycline treatment on OS (HR 0.82, 95% CI 0.56 - 1.18, p = 0.28). Conclusions: Our study demonstrated that anthracyclines may not be mandatory in the first-two lines of palliative chemotherapy for AN-MBC but may be more beneficial to ER-/Her2+ subtype patients.

Fatigue control in metastatic colon cancer treated with capecitabine and oxaliplatin.

e19628 Background: Fatigue is one of the most frequent symptoms in cancer patients, characterized by profound fatigue that is not relieved by rest. This symptom can be identified at the time of diagnosis and could affects up to 90% of patients undergoing cancer treatment. There are some instruments available in the literature that can characterize the presence of fatigue through clinical questioning. Methods: Considering the large population of patients with metastatic colorectal cancer treated with chemotherapy and the prevalence of fatigue in these patients, this study evaluated the presence of fatigue in 27 metastatic colon cancer patients before the first, second, third and fourth cycles of fist line palliative chemotherapy regimen containing CAPOX (capecitabine and oxaliplatin) by applying the evaluation questionnaire FACIT-F fatigue. Results: The results post Friedman chi-squared test demonstrated that there was no improvement of fatigue during these four cycles of CAPOX palliative chemotherapy (p=0,2574). The FACIT-G analysis demonstrated no worsening of quality of life (p=0,2411) during and between the four cycles of chemo. All different parameters included in FACIT-F questionnaires: emotional (p=0,2629), physical (p=0,3199), familiar (p=0,1456), functional (p=0,8662) and specific fatigue topic (p=0,7569) confirmed no difference between the cycles. Conclusions: Despite the metastatic stage of colon cancer patients and concurrent chemotherapy treatment, there was no fatigue improvement during the four first CAPOX chemo cycles courses and there was the maintenance of quality of life.