Eastern Cooperative Oncology Group Trial Research Articles

IFN-α in the treatment of melanoma.

Among the IFNs, IFN-α2 has been the most broadly evaluated clinically. At the molecular level, IFN-α has multiple effects in a variety of malignancies that range from antiangiogenic to potent immunoregulatory, differentiation-inducing, antiproliferative, and proapoptotic effects. A multitude of IFN-α2 regimens that may be classified as low dose, intermediate dose, and high dose have been evaluated as adjuvant therapy in melanoma. A durable impact on both relapse-free and overall survival was seen only with the regimen utilizing high-dose IFN-α2b tested in the Eastern Cooperative Oncology Group and intergroup trials E1684, E1690, and E1694 as adjuvant therapy for high-risk surgically resected melanoma (stage IIB or III). Adjuvant pegylated IFN-α2b has also been evaluated at maximally tolerable doses compared with the observation group in the European Organization for Research and Treatment of Cancer trial 18991 and has shown relapse-free survival benefits in patients with microscopic nodal disease.

How Much of a Good Thing? What Duration for Interferon Alfa-2b Adjuvant Therapy?

How Much of a Good Thing? What Duration for Interferon Alfa-2b Adjuvant Therapy?

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

AbstractWe determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML.

Differential effect of age on survival in advanced NSCLC in women versus men: Analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab

BackgroundThe impact of age on prognosis in advanced stage non-small cell lung cancer (NSCLC) may differ by sex. Patients and methodsEligible patients (N=1590) from E1594, a 4-arm platinum-based chemotherapy trial, and E4599 (carboplatin/paclitaxel±bevacizumab) chemotherapy arm were divided into male and female cohorts and separated into age groups of <60 or ≥60 years old. Eligible E4599 patients (N=850) were similarly separated by age and sex and by treatment (±bevacizumab). Survival was calculated separately for each cohort. ResultsThe median survival time (MST) for women ≥60 years old treated with chemotherapy alone on E1594 and E4599 was 11.6 months versus 9.0 months for women <60 (p=0.03). MST was 7.4 and 8.3 months for men ≥60 and <60 years old respectively (NS). In E4599 the age <60 by bevacizumab treatment interaction was statistically significant (p=0.03) for women (younger had greater benefit), with no age effect in men. ConclusionsIn this unplanned, exploratory subgroup analysis of advanced stage NSCLC ECOG trials, women ≥60 years old treated with chemotherapy live longer than men and younger women. In contrast, bevacizumab survival benefit was more pronounced in men of any age and in younger women on E4599.

Gemcitabine Alone Versus Gemcitabine Plus Radiotherapy in Patients With Locally Advanced Pancreatic Cancer: An Eastern Cooperative Oncology Group trial

Gemcitabine Alone Versus Gemcitabine Plus Radiotherapy in Patients With Locally Advanced Pancreatic Cancer: An Eastern Cooperative Oncology Group trial

S6-2: Patient-Reported Predictors of Early Treatment Discontinuation: NCIC JMA.27/E1Z03 Quality of Life Study of Postmenopausal Women with Primary Breast Cancer Randomized to Exemestane or Anastrozole.

Abstract Background: Patient-reported outcomes (PRO) assess symptom burden and health-related quality of life (HRQL) more accurately than clinical report. We previously found that treatment-emergent adverse events (CTCAE V3.0) did not impact efficacy in the main NCIC MA.27 trial, although many women discontinued treatment early. The purpose of this substudy was to obtain PROs in MA.27/E1Z03 participants to evaluate treatment-related side effects and HRQL between exemestane and anastrozole and to identify predictors of treatment discontinuation. Methods: The Eastern Cooperative Oncology Group trial (E1Z03) assessed PROs in a sample of MA.27 patients (N=686; 99.3% participation rate). Participants completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) pre-treatment and at months 3, 6, 12 and 24 to assess breast-cancer specific concerns, side effects of hormonal treatments and HRQL. We used 1) Wilcoxon rank sum test to compare treatment-related symptoms and HRQL between trial arms; 2) linear mixed effect models to test differences in changes of treatment-related symptoms and HRQL between trial arms; 3) linear regression to examine the effects of symptoms on HRQL and 4) adjusted Cox regression to assess predictors of treatment duration. Results: Participants included 371 women randomized to anastrozole and 315 randomized to exemestane. Demographic and disease characteristics were balanced between trial arms. Participants were a mean age of 65.6 yrs (SD=9.2), White (95.9%), ECOG PS of 0 (87.2%), stage T1 (75.5%) or T2 (22.7%), and stage N0 (73.9%) or N1 (16.3%). Prior treatments included partial mastectomy (65.7%), chemotherapy (27.8%) and radiotherapy (51.7%). Treatment-related symptoms measured by 23 items from the FACT-ES did not differ between treatment arms at months 3, 6, 12 and 24 and the timeline change of treatment-related symptoms was similar between treatment arms (p = ns). HRQL was significantly impacted by decreased libido, weight gain, feeling bloated, breast sensitivity, mood swings, irritability, join pain, nausea and bother by treatment side effects (p &amp;lt; 0.001). 248 participants were off-treatment by 4.1 yrs. A Cox model adjusted for other symptoms, demographic and disease characteristics indicated the hazard of discontinuing treatment early increased by 29% when the severity of being bothered by side effects at baseline increased by 1 point (HR=1.29, 95% CI:1.09−1.54). At baseline, patients with prior treatments or taking more medicines reported more bother by side effects (p &amp;lt; 0.001). Increased joint pain in the first 3 months after treatment was also associated with increased hazard of discontinuing treatment early (HR=1.13, 95% CI: 1.01−1.28). Conclusions: PRO assessment indicated comparable symptom burden and HRQL among postmenopausal women randomized to anastrozole or exemestane, with increasing symptom burden over time negatively affecting HRQL. Patients who 1) initiate an aromatase inhibitor (AI) with bother by side effects from prior treatment and concomitant medications and 2) experience increased joint pain during the first 3 months of AI therapy are at risk for early discontinuation of AI therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S6-2.

Development of the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM) Scale and Validation in the Eastern Cooperative Oncology Group Trial E1A05,

Abstract 4184 Introduction:FACT-MM was developed with the aim to create a disease-specific, patient-reported outcomes (PRO) measure as part of the FACT measurement system to assess multiple myeloma (MM)-related symptoms. Literature review identified 52 MM specific symptoms and concerns. 13 MM expert clinicians rated these 52 items on relevance to health-related quality of life (HRQL) for MM patients and added 11 items for comprehensive PRO assessment in MM. These 63 candidate items were rated by 13 MM patients recruited through the International Myeloma Foundation website. Disease-related symptoms and concerns were described and provided by patients through free-text comments. Information from both the MM expert clinician and MM patient surveys including free-text items was analyzed and 14 highest ranked items were selected for the FACT-MM. The FACT-MM subscale (score 0–56), the FACT-G physical and functional well-being subscales (score 0–28), and the FACT-Neurotoxicity (FACT-Ntx) subscale (score 0–44) was administered to 48 E1A05 participants to assess disease and treatment-related symptoms of patients with newly diagnosed MM receiving 8 cycles of VRd versus Vd. Methods: In this study, the first three of seven sequential assessments were evaluated: baseline, cycle 5 and end of treatment (after cycle 8 or early diconstinuation). Instruments were scored as per the FACT scoring guidelines. Descriptive statistics were provided for each timepoint and changes in scores from baseline. The Wilcoxon rank sum test was used to assess differences in scores by ISS stage and ECOG PS. Pearson correlation coefficients were obtained between the scores. Cronbach’s alpha was used to evaluate internal consistency of the FACT-MM. Results: At baseline and end of treatment, 46 and 41 patients, respectively, completed assessments. The FACT-MM demonstrated good to very good internal consistency (Cronbach alpha 0.79 – 0.89). The FACT-MM subscale was significantly correlated with the FACT physical and functional well-being subscales at baseline (r = 0.72), cycle 5 (r = 0.64; r = 0.49) and end of treatment (r = 0.72; r = 0.66). All scores declined modestly by cycle 5 and end of treatment from baseline. While sample size was limited, there appeared association with ECOG PS with higher scores for patients with PS 0 status. Conclusions: The 14-item FACT-MM scale is feasible for use to measure myeloma-related symptoms and has demonstrated acceptable psychometric properties based on findings from E1A05, an ECOG myeloma trial. Disclosures:Cella:Novartis: Research Funding. Fonseca:Consulting:Genzyme, Medtronic, BMS, Amgen, Otsuka, Celgene, Intellikine, Lilly Research Support: Cylene, Onyz, Celgene: Consultancy, Research Funding.

Gemcitabine Alone Versus Gemcitabine Plus Radiotherapy in Patients With Locally Advanced Pancreatic Cancer: An Eastern Cooperative Oncology Group Trial

The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer. Patients with localized unresectable adenocarcinoma of the pancreas were randomly assigned to receive GEM alone (at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest, then for 3 of 4 weeks) or GEM (600 mg/m(2)/wk for weeks 1 to 5, then 4 weeks later 1,000 mg/m(2) for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8 Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire was also performed. Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test). This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer, with acceptable toxicity.

Chemotherapy Definitions and Policies for Thymic Malignancies

Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection, which is the mainstay of the curative-intent treatment.1 However, approximately 30% of patients present with an advanced tumor at the time of diagnosis, with invasion of neighboring organs, dissemination to the pleura, the pericardium, or less frequently extrathoracic organs. In such cases, chemotherapy has been used both to reduce the tumor burden—possibly allowing subsequent surgery or radiotherapy—and to achieve prolonged disease control. Recurrence after resection may be similarly treated with chemotherapy. Thymic carcinomas, although rare, are usually already advanced at the time of presentation, and systemic therapy is important for almost all of these patients. Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospective trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma, and to a lesser extent thymic carcinoma, to various cytotoxic agents and combinations. However, details of patient selection are often lacking (either disease extent or general condition), and the intent of the treatment sequence is often vague. Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group (ITMIG) effort to develop a international prospective database of thymic tumors. The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment. Herein, we discuss additional points with regard to chemotherapy, including treatment sequence, general modalities, and impact of corticosteroids.

Motesanib and advanced NSCLC: experiences and expectations

Introduction: Benefits from conventional chemotherapy in NSCLC have plateaued. Accordingly, sizeable efforts have gone into developing novel therapies. Tumor angiogenesis mediated principally by VEGF has emerged as an alluring target because of its vital role in tumor growth, sustenance and metastasis. The Eastern Cooperative Oncology Group (ECOG) trial E4599 showed significant improvement in overall survival with addition of bevacizumab, a VEGF monoclonal antibody, to cytotoxic chemotherapy in metastatic NSCLC. A number of compounds targeting tumor angiogenesis have since gone into preclinical and clinical testing. The multifaceted nature of cancer has led to development of multitarget tyrosine kinase inhibitors (MTKIs) that target several pathways concomitantly. Motesanib, an orally administered potent small molecule, targets VEGFR 1 – 3, PDGFR and KIT. Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations.Areas covered: This review summarizes the background of angiogenesis and rationale for targeting the VEGF pathway in NSCLC. The authors also review recent clinical trial data evaluating motesanib.Expert opinion: VEGF is a validated target in NSCLC. In early trials motesanib has shown promising activity in NSCLC with tolerable toxicity profile. A Phase III trial with motesanib in combination with chemotherapy is ongoing.

Symposium zeroes in on new discoveries in breast cancer

Symposium zeroes in on new discoveries in breast cancer

Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi’s sarcoma: an Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial

Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Patients with advanced HIV-associated KS received paclitaxel (100mg/m(2)) by intravenous infusion over 3h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30%) had an objective response and median progression-free survival was 7.8months (95% confidence interval, 5.6, 21.0months). Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.

Sex Differences in Outcome with Bevacizumab Therapy: Analysis of Patients with Advanced-Stage Non-small Cell Lung Cancer Treated with or without Bevacizumab in Combination with Paclitaxel and Carboplatin in the Eastern Cooperative Oncology Group Trial 4599

E4599 compared carboplatin and paclitaxel with (PCB) or without (PC) bevacizumab in patients with advanced-stage non-small cell lung cancer. Bevacizumab improved overall survival. However, an unplanned subset analysis did not show a survival benefit for females treated with bevacizumab. Known prognostic factors and toxicities were compared by sex. Proportional hazards models of survival with multiple factor combinations were used to adjust for treatment effect. The analysis includes 850 patients. The median survival was 8.7 months (PC) versus 11.7 months (PCB) for males (p = 0.001) and 13.1 months (PC) versus 13.3 months (PCB) for females (p = 0.87). Progression-free survival and response rate on the PCB arm were 6.3 months and 29% for males and 6.2 months and 41% for females (p > 0.05). Progression-free survival and response rate on the PC arm were 4.3 months and 16% for males and 5.3 months and 14% for females (p > 0.05). No significant demographic differences were seen between the two arms for males, whereas fewer females on the PCB arm had liver metastasis (PCB 11.7% versus PC 23.2%, p = 0.003). Adverse events with a sex difference on the PCB arm included severe hypertension (males: 4.2%, females: 9.9%, p = 0.02), constipation (males: 1.4%, females: 4.7%, p = 0.05), and abdominal pain (males: 0.9%, females: 5.2%, p = 0.01). In the proportional hazards model adjusting for the other factors, the test for a sex by treatment interaction was not significant (p = 0.09). Multiple factors may contribute to the apparent sex-specific differences in efficacy of bevacizumab noted in this study.

Tipifarnib Is Well Tolerated as Maintenance Therapy In Acute Myeloid Leukemia (AML). Significant, but Non-Fatal, Hematologic Toxicity Not Ameliorated by Dose Reduction. Preliminary Results of the Phase III Intergroup Trial E2902

AbstractAbstract 3315The Eastern Cooperative Oncology Group (ECOG) trial, E2902, was a randomized phase III intergroup trial of the Farnesyl Transferase Inhibitor, R115777(Tipifarnib), as maintenance therapy for acute myeloid leukemia (AML). Patients (pts) with AML in remission after requiring salvage therapy (primary induction failure or second or subsequent remission) or over the age of 60 in first remission were eligible. A confirmatory bone marrow exam was required within 2 weeks prior to randomization. Pts were eligible if they were in a complete remission (CR) or morphologic remission (MR). Consolidation or post remission therapy prior to enrollment was allowed but not required. Pts who had received an allogeneic transplant in this remission were ineligible. Adequate blood counts (absolute neutrophil count >= 1000/mm3 and platelet count >=50,000/mm3), and normal renal, and hepatic function were required within 2 weeks of randomization.Pts were randomized to either receive tipifarnib twice daily (BID) or to observation. The main objective of this study was to compare disease free survival in the two groups. Although the study has completed accrual, an insufficient number of events have been recorded at this point to allow for evaluation of the survival data. However, toxicity data are now available. Between August 2004 and December 2009, 144 pts were accrued to the study. The median age of the pts is 70 (range 28–86). Seventy-three pts (51%) were male and 135 pts (94%) were white. Seventy-three pts were enrolled onto the treatment arm (Arm A) and 71 pts were enrolled onto the observation arm (Arm B). When the study was initially opened, pts on Arm A were treated with tipifarnib at a dose of 400 mg BID with dose reductions and interruptions defined per protocol for toxicity. After the first planned interim analysis, based on toxicity data, the ECOG Data Monitoring Committee recommended that the starting dose be decreased to 300 mg BID.The majority of pts enrolled on the study were in first CR (CR1) (Table 2). Among the 30 pts treated with the initial 400 mg BID dose, 23 pts (77%) had their dose held or reduced to a lower dose in the subsequent treatment cycles. For the 41 pts whose initial dose was 300 mg BID, 61% required either dose modification (n=19) or discontinued (n=6) due to toxicity.Table 1:Baseline characteristicsArm A 400 mg BID n=31Arm A 300 mg BID n=42Arm B Observation n=71CR116 (52%)34 (81%)47 (66%)>CR110 (32%)8 (19%)16 (23%)Unknown5 (16%)16 (11%)Table 2:ToxicityToxicity TypeArm A 400 mg n=31Arm A 300 mg n=41Arm B Observation n=69Grade (n)Grade (n)Grade (n)343434Hemoglobin116112Leukocytes241643Neutrophils58371Platelets410111115Cardiac-ischemia1Fatigue1Diarrhea1Nausea1Febrile neutropenia11Infection w/gr 3-4 neutrophils (ANC)1Infection Gr0-2 ANC113GGT1Hypokalemia1Confusion1Agitation1Neuropathy-sensory1Back pain1Worst degree Non Hematologic42911While non-hematologic toxicity was acceptable, significant hematologic toxicity was seen in pts treated at an initial dose of either 400 mg or 300 mg BID (Table 2). Of note, hematologic toxicity was also seen on the observation arm although less frequently than with both treatment doses. Non-hematologic toxicity was much less frequent overall and there were no significant non-hematologic toxicities in the observation arm. Reduction of the initial dose did not ameliorate either the hematologic or non-hematologic toxicity seen on the treatment arms. There was however no fatal toxicity at either dose level. Results of the randomization with respect to efficacy remain essential to determining the utility of this agent as maintenance therapy in AML. Disclosures:No relevant conflicts of interest to declare.

Combined Etoposide, Ifosfamide, and Cisplatin in the Treatment of Patients with Advanced Thymoma and Thymic Carcinoma. A French Experience

The value of a nonanthracyclin regimen in thymic carcinoma and malignant thymoma is not well defined. These regimens may be useful in some patients, particularly with cardiac diseases. The objective of this study is to evaluate the response rate, progression free survival, overall survival and toxicity of combined etoposide, ifosfamide, and cisplatin in patients with advanced thymoma and thymic carcinoma. From October 1995 to April 2001, 18 patients with advanced thymoma or thymic carcinoma were entered on trial, and receive etoposide (100 mg/m(2) on days 1-3), ifosfamide (1500 mg/m(2) on days 1-3), s and cisplatin (30 mg/m(2) on days 1-3). Cycles were repeated every 3 weeks for a total of six cycles. Among 16 evaluable patients, there were no complete responses and four partial responses (complete and partial responses rate, 25%; confidence interval [CI] 95, 7-48%). The median follow-up was 32.6 months (range, <9-84 months), and the median overall survival has not yet been reached because more than 50% of patients are still alive. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 93.8 and 78.1%, respectively. The toxicity was predominantly myelosuppresion and alopecia. The combined etoposide, ifosfamide, and cisplatin regimen has moderate activity in patients with advanced thymic tumors. Our results confirm the Eastern Cooperative Oncology Group trial published in 2001. Response rates appear to be lower to many phase II trials, but survival seems similar.

Use of germline polymorphisms in VEGF to predict tumor response and progression-free survival in non-small cell lung cancer (NSCLC) patients treated with sorafenib: Subset pharmacogenetic analysis of Eastern Cooperative Oncology Group (ECOG) trial E2501.

7607 Background: E2501 was a randomized discontinuation phase II study of sorafenib (S) versus placebo (P) in patients (pts) with metastatic NSCLC who have failed at least two prior chemotherapy re...

A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial

The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.

Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer

Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect. To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy. We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study. Only phase II and III randomised controlled clinical trials were included in the analysis. All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan). Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS). All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported. Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

Voluntary submission of biological specimens from cancer clinical trials: An update of the Eastern Cooperative Oncology Group experience

6597 Background: Recent advances in cancer therapy underscore the need to acquire biological specimens from participants in well-conducted clinical trials. The Eastern Cooperative Oncology Group (ECOG) has previously reported a high rate of assent to the banking of biological specimens from participants in ECOG led trials. Methods: Since November 2000, ECOG trials include the Intergroup Specimen Banking Committee (ISBC) consent form governing biological specimen use. Data collected at patient registration regarding assent to specimen submission for correlative projects and/or banking are maintained in a data-base at the ECOG Coordinating Center. These data include participant responses to all questions contained in the consent from, and can be associated with study specific information and demographic data. Results: From November 2000 to August 2008, 30,695 participants were accrued from both academic centers and community based practices to ECOG led trials that included a voluntary request for biological specimens for correlative research, banking, or both. Overall, of the 30,496 participants presented with a request for specimen banking, 88.0% agreed to do so. Variance in assent rates for banking was noted by disease type. Permission to bank specimens was provided by 93.8% of leukemia patients (pts), 93.5% of breast cancer pts, and 91% of gastrointestinal cancer pts, whereas 75.7% of thoracic cancer pts, 75.0% multiple myeloma pts, and 63% of pts on prevention trials agreed. Data from 12,605 participants presented with a protocol-specified correlative project consent form are currently being analyzed. Interactions based on disease type, age, gender, type of institution and phase of study will be evaluated for biological specimen acquisition for banking and correlative use. Conclusions: Overall, a high rate of assent is demonstrated for biological specimen acquisition for banking purposes from participants in ECOG led clinical trials. Differences in assent rates for banking are suggested based on disease types. Further study to better define associations for suboptimal participation and reasons for refusal are planned. No significant financial relationships to disclose.

The treatment of multiple myeloma using vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with high‐dose cyclophosphamide and α2β interferon versus VBMCP

A randomized controlled trial tested the hypothesis that aggressive initial therapy using high-dose cyclophosphamide (HiCy) and alpha(2)beta interferon (IFN) may be superior to standard combination alkylating agent regimens in the treatment of newly diagnosed myeloma. This Eastern Cooperative Oncology Group trial evaluated 268 previously untreated patients with active multiple myeloma randomized to vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) or VBMCP plus HiCy and recombinant IFN. The overall objective response was 62% in the VBMCP regimen and 68% in the VBMCP + HiCy + IFN group. The near complete response and complete response rates were 8.1% and 8.9%, respectively. Progression-free survival was 22.1 and 25.3 months, respectively. The median overall survival was 37.1 months for patients treated with VBMCP and 41.3 months for those treated with VBMCP + HiCy + IFN (P = .38). The 5-year overall survival rates were not significantly different between the 2 arms: 26.4% and 33%, respectively. Lethal toxicities occurred in 15 patients, including 10 from infection, but there was no significant difference in lethal toxicities between the 2 regimens. The study showed no significant benefit with the addition of HiCy and IFN to VBMCP.