Eastern Cooperative Oncology Group Poor Performance Status Research Articles

Risk factors of ifosfamide-related encephalopathy in adult patients with cancer: A retrospective analysis.

Ifosfamide, a widely used chemotherapeutic agent, has been frequently associated with encephalopathy. A larger-scale study was conducted to identify risk factors of ifosfamide-related encephalopathy, including hepatic function. Adult patients who had completed at least one cycle of ifosfamide between January 2008 and December 2010 were included. Those with renal failure or liver failure were excluded. Data were collected through chart review. Patients with encephalopathy and patients without encephalopathy were compared on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline serum creatinine (SCr) level, albumin level, white blood cell count, liver function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fisher's exact test, Student t test, and univariate and multivariate logistic regressions were used for analysis. This study enrolled 337 patients. Thirty-eight patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS; higher SCr level, white blood cell count, and aspartate aminotransferase level; and lower serum albumin level compared with patients without encephalopathy. Ifosfamide dosage, brain metastasis, and age were not significant risk factors. Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level contributed significantly to the risk. To date, this is the largest-scale study to have analyzed the risk factors of ifosfamide-related encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr level are significant risk factors of ifosfamide-related encephalopathy, whereas increased albumin level decreases the risk, consistent with previous reports. Higher aspartate aminotransferase levels have no significant impact. In contrast to previous studies, ifosfamide dosage and brain metastasis are not significant contributing factors.

Bi-weekly docetaxel and 5-fluorouracil: an effective and feasible treatment for advanced gastric cancer with poor performance status.

Background: The survival benefits from cytotoxic chemotherapy have been demonstrated in advanced gastric cancer (AGC). A large proportion of AGC patients initially present poor performance status (PS); however, most of the clinical evidence comes from trials on patients with good PS. A better-designed regimen is greatly needed for AGC patients with poor PS.Objective: To evaluate the efficacy and safety of a modified combination regimen with docetaxel plus 5-fluorouracil (5-FU) every two weeks as first-line treatment in AGC patients with poor PS.Methods: From September 2011 to December 2013, 12 patients diagnosed with AGC with Eastern Cooperative Oncology Group (ECOG) PS scores of 3 or 4 were included in this study. All the patients received docetaxel 60 mg/m2 on Day 1, 5-FU 400 mg/m2 intravenous (i.v.) bolus on Day 1, and a 46-hour continuous i.v. infusion of 5-FU 2400 mg/m2 every two weeks, until disease progressed or patients experienced unacceptable toxicity or declined treatment. Detailed clinical, pathologic and survival data were all recorded.Results: Eleven out of 12 patients were assessable for responses, whereas nine cases (75%) achieved partial response, one (8.3%) achieved stabilized disease, and one (8.3%) had progressive disease. The median progression-free survival was 6.5 months (95% CI: 4.8–8.2). The median overall survival was 12.0 months (95% CI: 9.0–15.0). The most common Grade 3/4 toxicities were anemia in seven patients (58.3%). No patient experienced febrile neutropenia.Conclusion: The novel modification of bi-weekly docetaxel and 5-FU is a promising treatment option for AGC with poor PS, showing great efficacy and acceptable toxicity.

Lung Cancer in Women: A Single Institution Experience with 50 Patients

Lung cancer is the most common cause of cancer-related death worldwide. The incidence of lung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate the clinical, pathological properties and survival data of female patients with lung cancer who were treated in our center. From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data were evaluated retrospectively. The median age was 61 (40-81). Forty patients (80%) were diagnosed with non small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patients were smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologic subtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The most common initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) and initial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followup period: 1 year overall survival (OS) was 68%, 2year overall survival was 36% and the median survival time was 19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weight loss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positive prognostic factor. In this study NSCLC sub-type, poor ECOG performance score, advanced stage, anemia and weight loss were prognostic factors in Turkish women with lung cancer.

A Single-Arm, Open-Label, Expanded Access Study of Vemurafenib in Patients With Metastatic Melanoma in the United States

This open-label, multicenter study was designed to allow access to vemurafenib for patients with metastatic melanoma, bridging the time between end of enrollment in the phase III registration trial (December 2010) and commercial availability following US Food and Drug Administration approval of vemurafenib for the treatment of unresectable or metastatic BRAF-mutated melanoma (August 2011). Eligible patients had metastatic melanoma with a BRAF mutation (detected by the cobas 4800 BRAF V600 Mutation Test). Unlike previous vemurafenib trials, patients with poor performance status (PS) and treated brain metastases were permitted. Enrolled patients received oral vemurafenib 960 mg twice daily. Of 374 patients enrolled at 29 US sites (December 2010 to October 2011), 371 patients received vemurafenib and were followed up for a median of 2.8 months (the study had a prespecified end upon vemurafenib approval and commercial availability). At baseline, most patients (75%) had stage M1c disease, and 19% had an Eastern Cooperative Oncology Group PS of 2 or 3; 72% of patients had received prior systemic therapy for metastatic melanoma, 27% received prior ipilimumab, and 29% radiotherapy for prior brain metastases. Because reassessment data to confirm response were not available for most patients, point estimates of objective response rate (ORR) are reported. Among 241 efficacy-evaluable patients, the ORR was 54% (median time to response, 1.9 months). The ORR in non-central nervous system sites in patients with previously treated brain metastases (n = 68) was 53%. The ORR in prior ipilimumab-treated patients (n = 68) was 52%. For patients with PS of 0 or 1 (n = 210) and 2 or 3 (n = 31), the ORRs were 55%, and 42%, respectively. The safety profile observed was consistent with that reported in previous studies. The number of patients with grade 3 or 4 treatment-related adverse events was higher in patients with PS 2 or 3 than in those with PS 0 or 1 (10% vs. 5%, respectively). Adverse events requiring a dose reduction (at least 1 level) occurred in 11% of patients, and 9 patients (2%) experienced events leading to vemurafenib withdrawal, including 2 with repeated QT interval prolongation. This study confirmed the established rapid and high tumor response rate achievable with vemurafenib in BRAF mutation-positive metastatic melanoma. Several groups not included in previous studies, including patients with previously treated brain metastases, Eastern Cooperative Oncology Group PS 2 to 3, or previous ipilimumab treatment had benefitted from vemurafenib similar to the overall population. No new safety signals were detected.

Clinical Outcomes and Prognostic Factors of Empirical Antifungal Therapy with Itraconazole in the Patients with Hematological Malignancies: A Prospective Multicenter Observational Study in Korea

PurposeTo identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies.Materials and MethodsThree hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled.ResultsThe overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ≥2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (≥4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity.ConclusionWe concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Early Relapse Of Follicular Lymphoma After R-CHOP Uniquely Defines Patients At High Risk For Death: An Analysis From The National Lymphocare Study

IntroductionDespite gains in survival with aggressive upfront treatments, such as R-CHOP (rituximab, doxorubicin, vincristine, prednisone) for follicular lymphoma (FL), and the implementation of rituximab maintenance, approximately 20% of patients will still experience progression of disease (POD) within 24 months of chemoimmunotherapy, as demonstrated by the PRIMA study and others (Salles et al, Lancet 2010; Press et al, JCO 2013). This suggests a high-risk group of patients warranting further study. We analyzed the National LymphoCare Study to identify patients with FL who are at high risk of death after treatment with R-CHOP. We aimed to define what factors constitute high-risk FL that would merit further clinical and biological characterization. MethodsEvaluable patients with stage II, III, and IV FL who were treated with R-CHOP in the first-line setting were included. Patients were excluded if the initial treatment strategy was watchful waiting or if there was POD prior to beginning first-line treatment. Two groups were defined: patients with POD/death ≤2 years from diagnosis (early POD group) and a reference group without POD/death within 2 years of diagnosis (Ref).Multiple logistic regression compared baseline characteristics by group. Survival probability was estimated by the Kaplan-Meier method. A Cox model evaluated the effect of early POD on overall survival (OS). The Pearson chi-squared test and multiple logistic regression with backwards stepwise selection were used to evaluate whether baseline characteristics differed by group. OS was estimated using the Kaplan-Meier method, and a time-varying Cox model was used to evaluate the relationship between progression time and OS. ResultsA total of 588 patients were analyzed. Similar to results from the PRIMA study, approximately 21% of patients (122/588) had early POD, while 71% (420/588) did not, and 8% (46/588) were lost to follow-up within 2 yrs. Early POD following R-CHOP was dramatically and significantly related to worsened OS, with a hazard ratio of 12.3 (95% confidence interval [CI] 6.1—24.9), compared with those not progressing. After adjusting for FLIPI, patients with early POD who were still alive within 2 years of R-CHOP (early POD—alive at 2 yrs) had worse OS compared with patients who did not progress within 2 years (Ref group) [HR = 4.76, 95% CI 2.95—7.69]. At 5 years, patients with early POD had OS of 50% compared with an OS of 95% in the Ref group (Table 1 and Figure 1). Multiple logistic regression analysis showed that high lactate dehydrogenase (LDH), poor Eastern Cooperative Oncology Group (ECOG) performance status, B symptoms, and bone marrow involvement were significantly associated with early POD (P<0.05). As an exploratory analysis, we evaluated maintenance and second-line treatments following R-CHOP. In the early POD group, 22% received maintenance rituximab, and 80% began second-line treatment, compared with the reference group, where 45% received maintenance rituximab, and 23% began second-line treatment. The impact of second-line autologous stem cell rescue or allogeneic transplant on survival is unknown because of the small numbers of patients in these groups.Table 1Survival in patients with FL treated with first-line R-CHOPN2-year OS(95% CI)5-year OS(95% CI)Early progressors (POD)12271%(61.5—78.0)50%(40.3—58.8)Ref group (Late/no POD)420 (102/318)100%95%(92.7—97.0) [Display omitted] ConclusionsRelapse of FL after first-line treatment with R-CHOP is associated with poor outcomes. However, POD within 2 years of R-CHOP defines a unique category of patients at substantially increased risk of death. In our unselected cohort of 588 patients, 63% (65/104) of deaths in 6 years of follow-up occurred in the early POD cohort. High LDH, poor ECOG performance status, B symptoms, and bone marrow involvement conferred a significantly high risk for early POD. These high-risk patients represent a distinct population that warrants further study in directed prospective studies of FL biology and clinical trials. Disclosures:Byrtek:Genentech, a member of the Roche group: Employment, Stock ownership Other. Dawson:Genentech, a member of the Roche group: Employment, Stock ownership Other. Flowers:Abbott, Celgene, Millennium/Takeda, Sanofi, Spectrum, Janssen: Research Funding; Celgene, Genentech Bio-Oncology: Consultancy. Link:Genentech: Consultancy; Millenium: Consultancy; Pharmacyclics: Consultancy; Spectrum: Consultancy. Zelenetz:GSK: Consultancy; Celgene: Consultancy; Cephalon: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Sanofi-Aventis : Consultancy; Genentech: Research Funding; GSK: Research Funding; Roche: Research Funding; Cancer Genetics: Scientific Advisor Other.

Extramedullary Disease Is Common In Newly Diagnosed AML But Has No Independent Prognostic Significance, Including CNS Involvement: Analysis Of 3,522 AML Patients Treated On Consecutive ECOG Trials 1980-2008

BackgroundExtramedullary disease (EMD) of acute myeloid leukemia (AML) was described decades ago but the incidence of this phenomenon and its prognostic impact are not clear. It is also uncertain whether every site of EMD has the same significance. This study explored these questions using a large cohort of AML patients treated on consecutive Eastern Cooperative Oncology Group (ECOG) frontline clinical trials. MethodsFor AML patients enrolled into ECOG clinical trials, the presence of EMD was captured at baseline on case report forms. From patients with newly diagnosed AML, age 15 and above, who were treated on 11 consecutive different clinical trials, we identified those with or without EMD, defined by physical examination, laboratory findings and imaging, without necessarily a biopsy. We used descriptive statistics to summarize patient and disease characteristics. Univariate analyses of potential prognostic factors were done. The Kaplan-Meier method was used to estimate median overall survival (OS) within each prognostic category and differences were explored using the log-rank test. Cox proportional hazards models were used to examine the effect of one-unit increases in continuous variables on OS and for multivariable analyses. Multivariate models were built using backward selection. Factors (or groups of factors) significant at the 0.10 level in univariate analyses were tested for inclusion in the model, and retained if they were significant at the 0.05 level. ResultsOf the 3,522 patients enrolled in 11 different AML clinical trials, we excluded 281; for diagnosis of other types of leukemia (n=220), no EMD evaluation at baseline (n=41) or no survival data (n=20). The overall incidence of EMD was 23.8% (770 out of the remaining 3,241 patients). The sites involved were: lymph nodes 367 (11.3%) patients, spleen 234 (7.2%), liver 173 (5.3%), skin 146 (4.5%), gingiva 104 (3.2%), central nerve system (CNS) 32 (1%), peripheral nerve system (PNS) 8 (0.2%) and other sites 134 (4.1%). In 65 cases (8.4%) EMD was confirmed by biopsy. Most of the patients (64.4%) had only one site of EMD, 163 (21.2%) had 2 sites, 75 (9.7%) - 3 sites, 28 (3.6%) - 4 sites, and 4 patients (0.5%) each had 5 or 6 sites.EMD patients compared to those without EMD; tend to be younger (median age 45.7 vs 52.9 years); male (57.7% vs 52%); poorer ECOG performance status (76.4% with ECOG 0-1 vs 85.9%) and with higher white blood cell count (WBC) at diagnosis (median of 41.6/µl vs 10.2/µl).In univariate analysis, having EMD was associated with a shorter OS (P=0.006). Examination of individual EMD sites revealed that skin (P=0.002), spleen (P=0.0002) and liver (P=0.0007) but not CNS (P=0.35), PNS (P=0.53), nodal involvement (P=0.85) and gingival hypertrophy (P=0.14), were associated with poorer OS.Using proportional hazards models for continuous factors, each additional site of EMD conferred a 9.4% increase in the risk of death.In a multivariable model, after adjusting for known prognostic factors (such as: age, WBC count and cytogenetic risk group), the presence of EMD, number of EMD sites and any specific EMD site were not independently prognostic. Of 165 patients with known favorable cytogenetics EMD was present in only 22 patients (13%). This group appeared to have a worse prognosis, but the numbers are too small for a definitive assessment (figure 1). [Display omitted] ConclusionsExtramedullary disease is common in newly diagnosed AML with an incidence of almost 24%, but CNS involvement is very rare (0.95%). In contrast to published data, no site of EMD was found to have an independent prognostic impact in multivariate analysis. This large dataset emphasizes the importance of evaluating large number of patients and considering all known risk factors in the multivariate analysis. Disclosures:No relevant conflicts of interest to declare.

The practice of nondisclosure of advanced cancer diagnosis in Singapore: a continuing challenge

The traditional family-centred approach to cancer management in Singapore often leads to nondisclosure of diagnosis to patients with advanced cancer. This study aimed to determine the rate of nondisclosure to such patients in Singapore, and compare it against the rate of nondisclosure to patients' families and that of a study conducted in 1992. Consecutive patients (n = 100) with advanced cancer who were referred to a palliative home care service in 2004 were studied retrospectively. Comparison between the 1992 and present study groups was performed using chi-square and Fisher's exact tests. Multivariate logistic regression was applied to patient age, Eastern Cooperative Oncology Group (ECOG) performance status, gender and ethnicity to identify factors associated with nondisclosure. The overall nondisclosure rate among patients with advanced cancer was 23% (23/100), compared to only 2% (2/99) among their families (p < 0.001). The nondisclosure rates among ECOG 0-2 and ECOG 3-4 patients were 11% (7/62) and 42% (16/38), respectively (p < 0.001). There was no significant improvement in the nondisclosure rate among ECOG 3-4 patients when compared to the 1992 study (p = 0.94). It was more likely for nondisclosure to occur among patients aged ≥ 70 years (p < 0.001; odds ratio [OR] 14.77, 95% confidence interval [CI] 3.68-59.26) and those with poor ECOG performance status (p = 0.019; OR 4.0, 95% CI 1.26-12.73). There was no significant association between nondisclosure and gender or ethnicity (p > 0.05). Disclosure of diagnosis to patients with advanced cancer remains a challenge in Singapore. The relationship between nondisclosure and advanced age, as well as nondisclosure and poor ECOG performance status, needs to be clarified with further studies.

Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?

e14583 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centers. Results: Of the 864 patients entered, 161 (18.6%) had an ECOG PS ≥ 2. In total, 95 (11.0%) were PS 2, 54 (6.3%) PS 3 and 12 (1.4%) PS 4. Chemotherapy was administered to 65 (68.4%) PS 2 and 17 (31.5%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (51.6% versus 86.8%, p&lt;0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (67.5% vs 81.1%, p=0.0057) or bevacizumab (31.3% vs 55.8%, p&lt;0.0001). Overall survival (OS) was reduced with declining PS, with medians of 28.7, 8.9, 3.5 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p&lt;0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.0 vs 3.5 months for untreated patients, p&lt;0.0001). At one and two years, 24 (28.9%) and 7 (8.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.

Changes in patient-reported outcomes in patients diagnosed with and treated for multiple myeloma in the Connect MM registry.

8586 Background: Little is known about the impact of treatment on patient-reported outcomes (PROs) and health-related quality of life (HRQoL) in multiple myeloma (MM) patients (pts). The change in PROs of MM pts between baseline and 1 year was assessed relative to their baseline International Staging System (ISS) stage and Eastern Cooperative Oncology Group (ECOG) performance status (PS) score. Methods: Connect MM is a prospective US registry of MM pts initiated in 2009. Clinicians reported pt demographics, ECOG PS score, and ISS stage. PROs were collected at baseline and at 1 year utilizing the Functional Assessment of Cancer Therapy (FACT)-MM, EQ-5D, and Brief Pain Inventory (BPI). Changes in FACT-MM, EQ-5D, and BPI scores were analyzed by ISS stage and ECOG PS score in 636 pts meeting CRAB criteria from 189 centers. Results: Most pts were male (58%) and white (84%). Mean age was 66 years (± 11). Pts were treated in community (81%), academic (17%), or veterans/military (2%) settings. ISS stages of pts were: I (29%), II (35%), and III (35%). ECOG PS scores were 0 (37%), 1 (49%), 2 (11%), and 3 (3%). Improvements in overall HRQoL as shown by the FACT-MM and FACT-General (G) total scores, were observed across all ISS stages (P = 0.03 to &lt; 0.0001) with no significant differences between stages. Improvements in FACT-MM and FACT-G total scores were observed with ECOG PS scores 1–3 (P = 0.03 to 0.005). Pts with poorer ECOG PS scores tended to have greater improvement in EQ-5D domains of mobility, self-care, and usual activities. HRQoL/functional ability improved in 4 of 5 FACT domains (except social/family; all others P &lt; 0.0001), and in 4 of 5 EQ-5D domains (except pain/discomfort; all others, P = 0.01 to &lt; 0.0001). BPI showed that overall average pain improved (P &lt; 0.0005) over 1 year, but statistically significant differences by ISS stage or ECOG PS score were not observed. Conclusions: Connect MM data showed that overall HRQoL of MM pts improved between baseline and 1 year, with a consistent benefit observed across pts with different ISS stages and ECOG PS scores. Additional analysis should examine which disease- and treatment-related factors are associated with these HRQoL improvements.

Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?

534 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centres. Results: Of the 679 patients entered, 129 (19.0%) had an ECOG PS ≥ 2. In total, 77 (11.3%) were PS 2, 41 (6.0%) PS 3 and 11 (1.6%) PS 4. Chemotherapy was administered to 55 (71.4%) PS 2 and 15 (36.6%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (55.0% versus 86.8%, p&lt;0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (38.0% vs 71.6%, p&lt;0.0001) or bevacizumab (15.5% vs 46.9%, p&lt;0.0001). Overall survival (OS) was reduced with declining PS, with medians of 31.2, 9.0, 3.0 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p&lt;0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.8 vs 4.1 months for untreated patients, p&lt;0.0001). At one and two years, 22 (31.4%) and 8 (11.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.

Leptomeningeal Carcinomatosis in Non–Small-Cell Lung Cancer Patients: Impact on Survival and Correlated Prognostic Factors

The incidence of leptomeningeal carcinomatosis (LC) has increased in patients with metastatic non-small-cell lung cancer (NSCLC) because of recent improvements in survival. The clinical features and prognostic factors of LC in NSCLC patients, however, have not been well identified. The aim of this study was to identify the clinical features and prognostic factors of NSCLC patients with LC. One hundred and forty-nine consecutive NSCLC patients with cytologically proven LC diagnoses between 2001 and 2009 at Samsung Medical Center were retrospectively reviewed. The median age was 58 years (range, 34-80) with most patients (135, 95%) having histology indicating adenocarcinoma. Twenty-six patients (17.4%) had LC at the initial presentation of lung cancer. Treatment for LC consisted of intrathecal chemotherapy (ITC) alone in 44 patients, ITC plus systemic therapy in 18 patients, ITC plus radiotherapy in 29 patients, all three treatments in 18 patients, and other treatments without ITC in 20 patients. Twenty patients received only supportive care. The median follow-up duration was 34 months and the median overall survival from diagnosis of LC was 14 weeks (95% confidence interval [CI] 12, 16). In univariate analysis, encephalopathy, Eastern Cooperative Oncology Group (ECOG) performance status, low initial cerebrospinal fluid (CSF) glucose, high initial CSF protein, high initial CSF white blood cell count, treatment with ITC, systemic therapy with epidermal growth factor receptor tyrosine kinase inhibitors or cytotoxic chemotherapy, whole-brain radiotherapy (WBRT), ventriculoperitoneal (VP) shunt operations, and negative cytologic conversion after ITC were identified as variables that had prognostic influence on survival. In multivariate analysis, poor ECOG performance status (p = 0.026), high protein level of CSF (p = 0.027), and high initial CSF WBC count (p = 0.015) remained significant predictors of poor prognosis for survival, whereas ITC (p < 0.001), EGFR-TKI use (p = 0.018), WBRT (p = 0.009), and VP shunt operation (p = 0.013) remained significant predictors of favorable prognosis for survival. Even though the prognosis of LC from NSCLC is poor, small subsets of these patients survive longer. Our results suggest that more active treatment strategies including ITC, WBRT, and EGFR-TKI use might improve clinical outcomes in NSCLC patients with LC and good performance status, low initial CSF protein and WBC counts.

The Incidence, Risk Factors, and Prognosis of Recurrent Venous Thromboembolism (VTE) in Patients with Advanced Solid Cancers Receiving Anticoagulation Therapy After the Diagnosis of Index Vte; A Korean Venous Thromboembolism Registry Study.

AbstractAbstract 2247 IntroductionPatients (pts) with cancer have been associated with increased risk of recurrent venous thromboembolism (VTE). However, few data are available regarding the recurrent VTE in Asian pts with advanced solid cancers. Thus, the aim of the study is to investigate the incidence and risk factors for recurrent VTE in pts with advanced solid cancers receiving anticoagulation therapy after index VTE. And, we also evaluate the prognostic impact of recurrent VTE on overall survival (OS) in this population. MethodsThis study was conducted using data from the web-based registry of the Korean Thrombosis Working Party (http://kdvt.chamc.co.kr), which is an ongoing, multicenter database for recruiting consecutive pts presenting with VTE. Pts were included in the study cohort if they had been diagnosed with recurrent/metastatic solid cancers between May 2004 and Dec 2011 and initiated anticoagulation therapy. Pts were excluded if they had received a diagnosis of hematologic malignancies, if solid cancers were not recurrent or metastatic disease, if index VTE was intra-abdominal venous thrombosis or vascular access-induced thrombosis, or if anticoagulation therapy was not instituted. Pts were also excluded if they were lost to follow-up within 1 week after initiating anticoagulation therapy. Maximal duration of anticoagulation therapy was 12 months and pts in whom anticoagulation therapy was stopped within 12 months were censored at the time of discontinuation. ResultsA total of 456 pts were included in this analysis. The median age was 65 (range, 27–91) years and 249 pts (55%) were male. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 or 1 in 185 pts (41%). The primary sites of tumor were breast in 22 (5%), genito-urinary tracts in 38 (8%), esophago-gastric in 76 (17%), colo-rectum in 81 (18%), hepato-biliary tracts in 37 (8%), pancreas in 66 (15%), and lung in 136 (30%). Palliative chemotherapy was administered in 328 pts (72%). The location of index VTE was isolated pulmonary embolism (PE) in 196 (43%), isolated lower-extremity deep venous thrombosis (DVT) in 169 (37%), and concomitant PE and DVT in 91 (20%). For initial anticoagulation therapy, low molecular weight heparin was administered in 362 pts (79%), and for long-term therapy, 306 pts (75%) received warfarin. The median duration of anticoagulation therapy after index VTE was 2.4 (range, 0.1–58.3) months.The 6-months and 12-month cumulative incidences of recurrent VTE were 22.4% (95% CI, 19.4–25.4) and 28.7% (95% CI, 24.0–33.4), respectively. In the multivariate analysis for identifying the risk factors associated with the development of recurrent VTE, pancreas (HR, 6.12; 95% CI, 2.00–18.73) and lung (HR, 2.98; 95% CI, 1.03–8.58) as the primary tumor site, poor ECOG PS (HR, 1.74; 95% CI, 1.14–2.67) and VTE initially presented with PE (HR, 2.29; 95% CI, 1.17–4.47) were independent risk factors for increased risk of recurrent VTE.With a median follow-up of 29.1 (range, 1.0–91.2) months, median OS was 11.9 (95% CI, 10.2–13.6) months. Pts with recurrent VTE had a significantly shorter OS than those without recurrent VTE (median, 8.4 vs. 13.0 months, P<0.001). In the multivariate model, occurrence of recurrent VTE was independently associated with the increased risk of death (HR, 1.39; 95% CI, 1.03–1.88). ConclusionAlthough Asian populations are thought to have lower risk for developing recurrent VTE, our study demonstrates that the incidence of recurrent VTE in pts with advanced solid cancers is comparable to that of Western populations. Lung or pancreas as a primary tumor site, poor PS, and initial presentation with PE are independent risk factors for recurrent VTE. Additionally, survival is adversely affected by recurrent VTE. Further studies are needed to validate the results of our study and to optimize the treatment strategies for improving treatment outcomes in advanced cancer pts. Disclosures:No relevant conflicts of interest to declare.

First-line single-agent chemotherapy for patients with recurrent or metastatic gastric cancer with poor performance status

Combination chemotherapy is a standard treatment approach in advanced gastric cancer. However, combination chemotherapy for advanced gastric cancer is often associated with severe treatment-related toxicities and most oncologists are reluctant to perform combination chemotherapy in patients with a poor clinical condition. We retrospectively investigated the efficacy and tolerability of single-agent chemotherapy in patients with recurrent or metastatic gastric cancer with poor performance status (PS). We reviewed advanced gastric adenocarcinoma patients who received first-line single-agent palliative chemotherapy due to poor PS between June 2006 and December 2010. A total of 125 patients with Eastern Cooperative Oncology Group (ECOG) PS 2–3, whose general condition did not allow combination chemotherapy, were enrolled. Four single agents were used: TS-1 (n=63), paclitaxel (n=42), irinotecan (n=15) and capecitabine (n=5). The median age was 66 years, with a range of 25–81 years. The percent response rate and rate of stable disease (SD) were 19.2 and 35.2%, respectively, giving a disease control rate of 54.4%. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.73–5.06). The median overall survival (OS) was 9.1 months (95% CI, 7.70–10.56) with a 1-year survival rate of 31.2%. Multivariate analysis demonstrated that the independent prognostic factors for OS were chemotherapy regimen (capecitabine) [reference: TS-1, hazard ratio (HR), 5.00; 95% CI, 1.81–13.81; P=0.002], no second-line chemotherapy (HR, 2.3; 95% CI, 1.48–3.57; P=0.001), bone metastasis (HR, 2.73; 95% CI, 1.22–6.09; P=0.014), ECOG PS 3 (HR, 38.10; 95% CI, 13.72–105.78; P=0.001), Glasgow prognostic score (GPS) ≥1 (HR, 1.88; 95% CI, 1.24–2.85; P=0.003) and chemotherapy response [SD + progressive disease (PD) + not evaluable (NE); HR, 2.37; 95% CI, 1.39–4.05; P=0.002)]. First-line single-agent palliative chemotherapy demonstrated a relatively good clinical efficacy for recurrent or metastatic gastric cancer patients with poor PS.

PD-0026 Quality of Life in Patients with Advanced Gastric Cancer Enrolled in the International, Phase 3 Granite-1 Study

ABSTRACT Introduction Advanced gastric cancer is an aggressive, difficult-to-treat disease associated with poor outcomes. Treatment options for patients who progress after first- or second-line chemotherapy are limited, particularly as many patients have poor performance status (PS) and are not eligible for additional chemotherapy. Advanced gastric cancer treatment options that improve outcomes without significantly decreasing quality of life (QoL) are needed. Methods In the randomized, double-blind, phase 3 GRANITE-1 study, patients aged ≥18 years with confirmed advanced gastric cancer, disease progression after 1 or 2 lines of previous systemic chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) PS ≤2 were randomized 2:1 to oral everolimus 10 mg/day plus best supportive care (BSC) or placebo plus BSC. Randomization was stratified by region (Asia [China, Japan, Korea, Taiwan, Thailand, and Hong Kong] vs rest of the world) and by the number of previous lines of systemic chemotherapy (1 vs 2). Study drug was continued until disease progression or unacceptable toxicity. ECOG PS was assessed at baseline, every 2 weeks for the first 4 weeks, and every 4 weeks thereafter until the end of treatment. The European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 QoL questionnaire and gastric-specific STO22 module were completed at the start of treatment and every 4 weeks thereafter until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included the time to definitive deterioration of ECOG PS, defined as a decrease of ≥1 category and no subsequent improvement, and the time to a definitive 5% deterioration in the global health status/QoL and physical, social, and emotional functioning scales of the QLQ-C30 questionnaire. Results A total of 656 patients (median age, 62.0 years; 73.6% male; 91.9% with ECOG PS ≤1) were enrolled in the study and received everolimus (n = 439) or placebo (n = 217). Median OS was 5.39 months with everolimus and 4.34 with placebo (HR for OS, 0.90; 95% CI, 0.75-1.08; P = 0.1244). The median time to definitive deterioration in ECOG PS by ≥1 category did not differ between treatment groups (2.30 months with everolimus vs 2.23 months with placebo; HR, 0.96; 95% CI, 0.76-1.20; P = 0.6925). A trend for slightly longer time to definitive 5% deterioration in global QoL was observed with everolimus vs placebo (median, 1.51 months vs 1.45 months; HR for definitive 5% deterioration from baseline, 0.84; 95% CI, 0.69-1.03; P = 0.0936). Trends for slightly longer time to definitive 5% deterioration in the social (HR, 0.87; 95% CI, 0.70-1.09; P = 0.2108) and emotional (HR, 0.83; 95% CI, 0.67-1.02; P = 0.0735) functioning scales were also observed; no difference between treatment groups was detected for physical functioning (HR, 0.95; 95% CI, 0.78-1.15; P = 0.5711). Over time, everolimus recipients had higher mean scores for the emotional functioning subscale of the QLQ-C30 and lower mean scores (i.e., lower level of symptoms) for the pain and reflux subscales of the STO22 module. Conclusion Everolimus did not cause significant deterioration in ECOG PS or QoL in patients with previously treated advanced gastric cancer.

Clinical Utility of the Pretreatment Glasgow Prognostic Score in Patients with Advanced Inoperable Non-small Cell Lung Cancer

Traditional tumor-based staging systems provide limited information on the best treatment option for individual patients with advanced inoperable non-small cell lung cancer (NSCLC). The Glasgow prognostic score (GPS) reflects the host systemic inflammatory response and is a validated independent prognostic factor in these patients. The aim of this study was to examine the clinical application of the pretreatment GPS in a mature cohort of patients with inoperable NSCLC. The data of 261 patients with inoperable NSCLC were collected prospectively and before treatment. Information on patient demographics, body mass index, performance status (PS), the modified Glasgow prognostic score (mGPS), the prognostic index, and treatment received were included. The majority of patients were aged 65 years or older (68%), were men (59%), had a body mass index more than 20 (89%), and an Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1 (54%). Most patients had a pretreatment mGPS = 1 (62%) and pretreatment prognostic index = 1 (56%). During the follow-up period, 248 (95%) patients died, 246 from their disease. The median survival was 8 months. On multivariate analysis, age (p = 0.001), ECOG-PS (p < 0.05), mGPS (p < 0.0001), and tumor stage (p < 0.0001) were independently associated with cancer-specific survival. Using 5-year cancer-specific mortality as an end point, the area under the receiver operator curve was 0.735 (95% confidence interval [CI], 0.566-0.903; p = 0.024) for the mGPS, 0.669 (95% CI, 0.489-0.848; p = 0.106) for ECOG-PS, and 0.622 (95% CI, 0.437-0.807; p = 0.240) for tumor, node, metastasis stage. Patients with an increased mGPS were more likely to have a poorer ECOG-PS (p < 0.05), an increased white cell count (p < 0.05), and received palliative treatment (p < 0.05). The pretreatment mGPS is a useful and important predictor of cancer-specific survival in patients with inoperable NSCLC. Basing clinical assessment on the mGPS has implications for the routine monitoring and treatment of the patients.

Very poor performance status elderly patients with aggressive B cell lymphomas can benefit from intensive chemotherapy

Very poor performance status elderly patients with aggressive B cell lymphomas can benefit from intensive chemotherapy

Phase II trial of single-agent oral vinorelbine in elderly (≥70 years) patients with advanced non-small-cell lung cancer and poor performance status

BackgroundElderly patients with advanced non-small-cell lung cancer (NSCLC) with poor performance status (PS) are a special population requiring particular attention. Single-agent oral vinorelbine could be an attractive option. Patients and methodsA total of 43 patients with stage IIIB–IV NSCLC and Eastern Cooperative Oncology Group (ECOG) PS of two or more with good functional status were prospectively recruited. Oral vinorelbine was administered at the dose of 60 mg/m2 on days 1–8 every 3 weeks. Primary end points were response rate and safety. ResultsOverall response rate was 18.6% with 8 partial responses; 18 of 43 (41.8%) experienced stable disease lasting >12 weeks and 17 of 43 (39.6%) disease progression for an overall clinical benefit of 60.4%. Median time to progression was 4.0 (range 2–22) months and median overall survival 8.0 (range 3–35) months. Treatment was well tolerated. Of 187 cycles, we did not observe any grade 3/4 toxicity with the exception of a single not-febrile G3 neutropenia. Regardless of severity, main toxic effects observed were nausea in 48.1% and vomiting in 22.9% of patients, anemia in 43.2%, fatigue in 32.6% and leukopenia in 23.2%. ConclusionSingle-agent oral vinorelbine is extremely safe in elderly patients with advanced NSCLC and ECOG PS of two or more and may represent a valid option in this very special population.

First-Line Gefitinib Treatment for Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status

Best supportive care only is recommended for patients with advanced non-small cell lung cancer (NSCLC) with poor performance status (PS) of Eastern Cooperative Oncology Group 3 or 4. Recently, the possibility of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy has been reported for poor PS patients harboring EGFR mutations. We retrospectively analyzed 74 patients with advanced NSCLC who were treated with first-line gefitinib during hospitalization for Eastern Cooperative Oncology Group PS 3 or 4. All patients were classified according to three clinical parameters: smoking history, gender, and histology type. The median age was 64 years (range, 35-86 years). The proportions of females, never smokers, and adenocarcinoma were 51.4%, 54.1%, and 78.4%, respectively. An overall response rate, median progression-free survival (PFS), and median overall survival (OS) was 27.0%, 32 days (95% confidence interval [CI], 22-48 days), and 61 days (95% CI, 7-115 days), respectively. Female gender, never smoking, and adenocarcinoma histology were strong predictors of tumor response. Never smoking and adenocarcinoma were independent predictors of better PFS but not of OS. Seven patients experienced treatment-related adverse effects of grade 3 to 4, which included anorexia (n = 2), pneumonitis (n = 4), and elevated liver enzymes (n = 1). Never-smoker females with adenocarcinoma exhibited a response rate of 50.0%, median PFS of 130 days (95% CI, 51-209 days), and median OS of 236 days (95% CI, 150-322 days). Gefitinib may provide clinical benefits for patients with NSCLC with poor PS who were selected according to clinically favorable parameters.

Clinical Outcomes of Patients With Breast Cancer in a Phase I Clinic: The M. D. Anderson Cancer Center Experience

Purpose Patients with metastatic breast cancer (MBC) refractory to standard therapy have a poor prognosis. We assessed prognostic factors and clinical outcomes for patients with MBC referred to a phase I clinic focused primarily on targeted agents. Patients and Methods We reviewed the medical records of sequential patients with MBC who presented to our phase I clinic between September 2004 and May 2008 to assess baseline patient characteristics, overall survival (OS), and clinical benefit. Results A total of 92 patients were identified, with a median age of 53 years (range, 28–83 years). The median number of previous therapies was 5 (range, 1–16 therapies). Of 92 patients, 78 were eligible for and offered ≥ 1 phase I clinical trial. With a median follow-up of 7.4 months, the median OS was 6.7 months (95% CI, 5.2–9.7). In multivariate analysis, independent factors predicting shorter survival were ≥ 10 previous treatments (vs. < 10 previous treatments; hazard ratio [HR], 3.27; 95% CI, 1.37–7.81; P = .008), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2/3 (vs. 0/1; HR, 2.92; 95% CI, 1.28–6.66; P = .01), and albumin level < 3.5 g/dL (vs. > 3.5 g/dL; HR, 2.88; 95% CI, 1.41–5.89; P = .004). Conclusion Patients with locally advanced or metastatic breast cancer referred for our phase I studies had a median survival of 6.7 months. Heavily pretreated disease, poor ECOG PS, and/or low albumin levels were associated with significantly shorter survival in a multivariate analysis.