Good Performance Status Patients Research Articles

Emepepimut-S for non-small cell lung cancer

Introduction: Immunotherapy as a possible therapeutic option for cancer has been of great importance due to the innovative development of vaccines. Various molecules have been tested and emepepimut-S (Biomira Liposomal Peptide 25 (BLP 25)) has emerged as an option, particularly in lung cancer.Areas covered: A PubMed literature and ClinicalTrials.gov search was conducted using the terms: emepepimut, BLP25, NSCLC, cancer immunotherapy, cancer vaccine and MUC1. This review covers how emepepimut-S acts against the mucin 1 (MUC1) tumor-associated antigen producing a cellular immune response against the cells that express MUC1 and the most important clinical data available that led to the ongoing Phase III trial.Expert opinion: The results obtained in the Phase I/II trials are promising, showing a favorable toxicity with a benefit in survival in NSCLC patients. As future trials develop, demonstration of the long-term survival benefit, understanding of the various mechanisms of immune response initiated by the drug and the selection of patients that will highly benefit from the immunotherapy will be elucidated. The safety and extension in survival makes emepepimut-S a very interesting drug and could, therefore, offer a possibility of treatment and maintenance, particularly for good performance status patients with locally advanced NSCLC.

Factors associated with adherence to chemotherapy guidelines in patients with non-small cell lung cancer (NSCLC).

7067 Background: Evidence-based guidelines recommend chemotherapy for medically fit NSCLC stage II-IV patients. Understanding the extent to which practice is consistent with guidelines as well as the compliance-associated factors is often not done because performance status (PS), a key clinical component in assessing chemotherapy appropriateness, is typically missing from claims-based datasets. Among a cohort of patients with known PS, we describe chemotherapy use concordance with ASCO guidelines and identify patient and other factors associated with guideline adherent use. Methods: A cohort of insured patients in a managed care environment, ages 50+, stage II-IV NSCLC between 2000-2007 identified via a tumor registry (n=406). Chart abstracted PS, automated medical claims, census tract information, and travel distance, linked to tumor registry data. Chemotherapy was considered recommended for patients with good (0-2) PS. Multivariate models were fit to evaluate characteristics associated with chemotherapy use. Results: Overall compliance with chemotherapy guidelines was 71%. Significant (p<0.05) predictors of chemotherapy underuse (19%) included increasing age (odds ratio [OR], 1.09), increasing income (OR, 1.02), diagnosed prior to 2003 (OR, 2.05), lower college graduation rate (OR, 0.93) and vehicle access in the patient’s neighborhood (OR, 6.96). Significant predictors of chemotherapy overuse (10%) included decreasing age (OR, 0.92), diagnosed after 2003 (OR, 3.24), lower college graduation rate (OR, 0.89) and increasing income in the patient’s neighborhood (OR, 1.05). Conclusions: Among NSCLC patients, almost one third do not receive chemotherapy concordant with guidelines. Care concordant with guidelines is influenced by the patient’s age, and economic considerations such as income, education, and presence of transportation barriers. For the 219,440 people in the US diagnosed with lung cancer there are opportunities to increase both up-front curative and palliative care for good PS patients, and to diminish chemotherapy use for poor PS patients with no medical harm, better use of hospice, and fewer costly end of life hospitalizations.

Third-line or fourth-line chemotherapy in non-small-cell lung cancer patients with relatively good performance status

Background Our aim here was to explore treatment efficacy of pemetrexed and docetaxel in non-small-cell lung cancer patients who had failed previous chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Methods We retrospectively reviewed clinical data of our non-small-cell lung cancer patients who received third- or fourth-line chemotherapy with pemetrexed or docetaxel in our institution from January 2006 to December 2009. Results One hundred and twenty-three patients received treatment, including 85 patients with pemetrexed treatment and 38 patients with docetaxel treatment. There was no difference in tumor response rate and toxicity profiles when using pemetrexed as third- or fourth-line treatment, neither was there difference in docetaxel treatment of third- versus fourth-line treatment. There was also no difference between docetaxel and pemetrexed in response rate and control rate when they were used as fourth-line treatment. However, docetaxel used in fourth-line treatment had higher incidence of neutropenia and more frequent need of granulocyte colony-stimulating factor support compared with pemetrexed in fourth-line treatment. Median progression-free survivals (PFSs) were 2.6 months and 3.8 months when using pemetrexed as third- and fourth-line treatment, respectively ( p = 0.417). Median PFSs were 3.8 months and 4.8 months when using docetaxel as third- and fourth-line treatment, respectively ( p = 0.882). There was also no difference in PFS between pemetrexed and docetaxel, both in third- and fourth-line treatment. Median survivals were 13.4, 12.2, 13.2, and 13 months for pemetrexed in third-line, fourth-line, and docetaxel in third-line and fourth-line treatment, respectively. Conclusion This retrospective study of pemetrexed and docetaxel showed relatively safe toxicity profile, reasonable response rate, and long survival when used as third- and fourth-line chemotherapy. Thus, it is reasonable to give good performance status patients third- and fourth-line chemotherapy. A phase III randomized trial is needed for better clarification of these issues.

Patterns of Recurrence in Glioblastoma Multiforme following Concomitant Chemoradiotherapy with Temozolomide

Introduction: The current standard treatment for good performance status patients with glioblastoma multiforme is maximal surgical resection followed by concomitant chemoradiotherapy using temozolomide (RT-TMZ). Although pathological specimens often confirm widespread tumour involvement, 90% of recurrences are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of recurrence following RT-TMZ.

How I treat HIV-associated multicentric Castleman disease

HIV-associated plasmablastic multicentric Castleman disease is an increasingly frequent diagnosis. Kaposi sarcoma herpesvirus is found in the monotypic polyclonal plasmablasts that characterize this disease. Unlike Kaposi sarcoma, the incidence does not correlate with CD4 cell count or use of highly active antiretroviral therapy. It is a relapsing and remitting illness, and diagnostic criteria are emerging that define disease activity based on the presence of a fever and raised C-reactive protein coupled with a list of clinical features. Treatment protocols increasingly stratify therapy according to performance status and organ involvement. I advocate rituximab monotherapy for good performance status patients without organ involvement and rituximab with chemotherapy for more aggressive disease. The success of antiherpesvirus agents in controlling active disease is limited, but valganciclovir may have a role as maintenance therapy in the future.

Tracheal cancer: Role of radiation therapy

Purpose To assess the results of tracheal cancer patients treatment and factors influencing prognosis. Background Primary malignant neoplasms of the trachea are rare. The treatment of choice for tracheal carcinomas is resection. Radiation therapy is recommended as a part of radical treatment or for palliation of symptoms. Materials and methods Between 1962 and 2006, 50 patients diagnosed with tracheal cancer were treated at the Centre of Oncology in Krakow. The analysis focused on locoregional recurrence-free survival (LRRFS), disease free survival (DFS) and overall survival (OS). Survival rates, univariate and multivariate analyses of prognostic factors were performed using the Kaplan–Meier method, the log rank test and Cox's proportional hazard method, respectively. For over 40 years, patients were treated using different modalities: surgery followed by radiotherapy (6%), radiotherapy (78%), chemoradiotherapy (8%), and symptomatic treatment (8%). Results The 5-year LRRFS was 18%, DFS was 15% and OS was 17%. gender (favoured females) was the only prognostic factor for LRRFS. For OS, the independent prognostic factors were performance status (favoured Karnofsky higher than 80), stage and year of start of the treatment (later than 1988 vs. earlier – 5-year OS 20% vs. 12%). 5-year OS in the following (strongly differentiated over the time) treatment modalities were: surgery followed by radiotherapy (66%), radiotherapy (16%), chemoradiotherapy (0%), and symptomatic treatment (0%). Of 44 patients treated with radiotherapy symptomatic partial response was observed in 32 patients and follow-up imaging studies revealed complete response in 5 patients, partial response in 25, stable disease in 4 or progressive disease in 4. Conclusions Radical treatment in patients in early stage and good performance status seems to be correlated with the improvement of survival. However, despite the fact that results of treatment are poor, radiotherapy offers symptomatic improvement.

HRQoL changes, mood disorders and satisfaction after treatment in an unselected population of patients with lung cancer

This study intended to explore the impact of the first treatment modality on health-related quality of life (HRQoL), mood disorders and mastery in an unselected population of patients with primary lung cancer and to judge patient satisfaction with treatment. An unselected group of 479 patients with newly diagnosed lung cancer in Southern Norway (Agder counties) were included prospectively from June 2002 to June 2005, collecting data on histology, treatment options, HRQoL, mood disorders and mastery at baseline as well as satisfaction with treatment, and changes in HRQoL and mood disorders after finishing the first treatment modality. After finishing the first treatment modality, patients experienced a worsening of nine HRQoL parameters and an improvement in one. Patients in good performance status experienced reduced physical and role function, and if in reduced performance, improved emotional and role function. Patients with mood disorders experienced reduced anxiety and depression, anxious patients experienced reduced neuropathies, and depressed patients experienced improved social functioning and appetite. Half of the patients treated actively were definitely positive to repeat the same treatment again compared with only 15% in the best supportive care group. Surgery was associated with reduced role function and increased dyspnoea, radiation was associated with increased fatigue, and chemotherapy in small cell lung cancer (SCLC), to a larger extent, was associated with alopecia than in non-SCLC (NSCLC). The development of many HRQoL parameters after the first treatment modality in an unselected population of patients with primary lung cancer seemed, at large, well correlated to general disease progression and to well-known treatment side effects. However, reduced role function after lung surgery, and reduced anxiety and depression in patients with mood disorders at baseline might be surprising. Patient satisfaction with treatment was surprisingly good. Several findings in this study may help clinicians to improve their handling of patients with lung cancer.

Gastrointestinal Cancer Educational Case Series: The History and Management of Complex Cases in GI Oncology. A 72 Year-Old Man with Metastatic Gastric Cancer

Gastric cancer is the third most common cancer worldwide and the second leading cause of cancer deaths. Appropriate staging and treatment options relate to the stage of disease and performance status of the patient. Here we present the case of a 72 year old male, with an initial presentation of apparently locally advanced gastric cancer. On discovery of metastatic disease, the utility of palliative gastrectomy, and first and second line chemotherapy are discussed. This case demonstrates the potential value of sequential lines of chemotherapy in good performance status patients with advanced gastric cancer. Further research will be necessary in order to assess the utility of newer targeted agents in this setting.

Clinical characteristics, univariate, and multivariate Cox model analysis of long-term (&gt; 3 years) survivors of stage IV metastatic breast cancer treated on phase II or III North Central Cancer Treatment Group (NCCTG) trials.

1157 Background: In the absence of curative treatment for the majority of patients with metastatic breast cancer (MBC), the goal of therapy is focused on symptom control, improved quality of life, and prolongation of survival. Past studies have demonstrated a subset of patients that can achieve long-term survival who in general tended to be young patients with good performance status, fewer sites of metastases and smaller disease burden. An update of characteristics of long-term survivors is necessary as the MBC patient population and treatment options have changed over the last decade. Methods: We reviewed phase II and III trial data for 1,747 patients from 23 NCCTG MBC trials that enrolled patients from 1996 to 2008. We defined patients with survival beyond 3 years from the initiation of systemic treatment of breast cancer as long-term survivors (3YLTS). Univariate association between 3YLTS status and baseline demographics were performed using a t test for age and tumor size and Chi- square test for categorical covariates, with p < 0.05 used to denote statistical significance. Univariate and multivariate Cox's models were used to assess the association between overall survival time and baseline patient characteristics. Results: A total of 294 of 1,747 (16.8%) patients were 3YLTS. Multivariate Cox model demonstrated that patients with first line metastases (hazard ratio (HR) 0.65), metastasis to bone (HR 0.78) and positive ER/PR status (HR 0.58) tend to live longer. Patients with ECOG performance status of 1 or 2 (HR 1.58), >4 sites of metastatic disease (HR 2.00), liver metastasis (HR 1.30), prior radiotherapy (HR 1.55), and prior chemotherapy (HR 1.43) did worse overall. All values are statistically significant. Age did not play a statistically significant role. Conclusions: Good performance status patients with fewer metastatic sites and ER-/PR-positive tumors tend to live longer. Age was not associated with overall survival. Partial support provided by NCI (CA25244) and Breast Cancer Research Foundation. No significant financial relationships to disclose.

Chemoradiation in Pancreatic Adenocarcinoma: A Literature Review

Adenocarcinoma of the exocrine pancreas has an annual incidence of 7,400 cases in the U.K. In comparison with other common cancers of solid organs, namely, breast, colorectal, and prostate cancer, pancreatic cancer has a high morbidity and mortality. Radical resection is possible in only 15%-20% of patients, and only 3%-4% of all patients presenting with this condition achieve long-term control and cure. Various strategies in the form of neoadjuvant and adjuvant treatment have been employed over the years to improve outcome, with limited success. Systemic chemotherapy remains the gold standard in the metastatic setting in good performance status patients, and adjuvant chemotherapy after resection of localized and locally advanced cancer has been found to improve outcome. The role of radiotherapy, however, remains controversial and is an area that merits further investigation in well-conducted multicenter trials at various stages of the disease in combination with systemic agents and exploiting recent advances in the delivery of radiotherapy. In this article, we review the published literature on the use of chemoradiation as a modality in various stages of pancreatic adenocarcinoma and highlight areas that future trials in this field should target for a way forward in this malignancy.

Elevated Serum NSE in Inoperable Non-Small-Cell Lung Carcinoma (NSCLC) Is Associated with a Better Response but Worse Prognosis

The aim of the study was to evaluate the predictive and prognostic values of elevated serum levels of selected cancer markers (NSE, Cyfra 21-1, CEA, ferritin, free beta-hCG, LDH) in patients with inoperable non-small-cell lung cancer (NSCLC). We investigated a group of 79 patients (49 men and 30 women) with NSCLC. Multivariate regression analysis showed response in patients with NSE > 12.5 ng/ml (p = 0.002), good performance status (p = 0.007) and elderly patients (p = 0.005). However, elevated NSE adversely affected the prognosis. Median survival in patients with NSE < 12.5 ng/ml, 12.5-20.0 ng/ml and > 20.0 ng/ml was 13.3, 11.3 and 6.7 months, respectively (p = 0.004). The negative effect of elevated NSE was independent of the response category. Univariate regression analysis showed that the following factors had a significantly negative effect on the prognosis: performance status, stage IIIB or IV, weight loss of > 10%, NSE > 20 ng/ml, Cyfra 21-1 > 10 ng/ml, CEA > 3 ng/ml, ferritin ratio > 1 and LDH > 480 IU/l. Multivariate analysis showed an independent adverse prognostic effect of stage IIIB or IV and elevated ferritin.

A Phase I Study of Gefitinib with Concurrent Dose-Escalated Weekly Docetaxel and Conformal Three-Dimensional Thoracic Radiation Followed by Consolidative Docetaxel and Maintenance Gefitinib for Patients with Stage III Non-small Cell Lung Cancer

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

A Phase II Study of Concurrent Chemoradiation with Weekly Docetaxel, Carboplatin, and Radiation Therapy Followed by Consolidation Chemotherapy with Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)

The current standard of care for good performance status patients with locally advanced non-small cell lung carcinoma is concurrent chemoradiation, although a clearly superior regimen has not been identified. Docetaxel has been shown to possess good single-agent activity against non-small cell lung cancer (NSCLC) and radiosensitizing properties, both alone and synergistically with carboplatin. We undertook this phase II study to determine the safety and efficacy of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation for the treatment of locally advanced NSCLC. Sixty-seven patients having previously untreated stage IIIA or IIIB unresectable NSCLC were enrolled, with 61 patients evaluated for endpoints. Docetaxel 20 mg/m IV infusion over 30 minutes followed by carboplatin area under the curve = 2 over 30 minutes was administered weekly during concurrent thoracic radiotherapy. After 3 week rest, consolidation docetaxel 75 mg/m(2) IV infusion over 60 minutes and carboplatin area under the curve = 6 over 30 minutes was administered every 3 weeks for two cycles. Concurrent thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 d/wk for first 5 weeks) followed by 18 Gy boost (2.0 Gy fractions 5 d/wk for 2 weeks) for a total dose of 63 Gy. One and 2 years overall survival rates were 45 and 20%, respectively. Progression free survival at 1 year was 27%. Median survival time was 12 months. Median time to progression was 8 months. The primary hematologic toxicity was leukopenia. The primary nonhematologic toxicity was esophagitis. The administered regimen of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation has acceptable toxicity profile. However, the overall survivals at 1 and 2 years are somewhat disappointing.

Topotecan consolidation after etoposide platinum for limited stage small cell lung cancer patients who do not receive prophylactic cranial irradiation

7553 Background: Small cell lung cancer (SCLC) accounts for approximately 15% of new lung cancer diagnoses in the US and about one third of patients present with limited stage (LD-SCLC). Concurrent chemoradiotherapy followed by prophylactic cranial irradiation (PCI) is standard and produces long-term survival in up to 25% of good performance status (PS) patients. Some patients refuse or are ineligible for PCI resulting in poorer outcome. Topotecan is active against SCLC and crosses the blood brain barrier suggesting that it might reduce brain metastases in this group. This phase II trial was designed to explore that possibility. Methods: Eligible patients had declined or were ineligible for PCI after completing standard platinum etoposide chemotherapy with concurrent radiotherapy for LD-SCLC with at least a partial response (PR), had recovered from toxicity with PS 0–1, and had no evidence of brain metastases. Patients received 1.5 mg/m2/day topotecan IV for 5 consecutive days every 21 days for four cycles. Primary endpoint was incidence of brain metastases with secondary endpoints overall and progression-free survival and toxicity. Results: Twenty patients enrolled between November 1999 and May 2006. 17 patients (85%) completed 4 cycles of topotecan. Brain metastases developed in 6 patients (30%) at a mean of 5.3 months (range 84–324 days). Median survival was 25.9 months with median PFS 462 days. At final data analysis, eight patients (40%) were alive without evidence of disease at 19 to 92.6 months. Topotecan was well tolerated with grade 3/4 hematologic toxicity in 13 patients (65%) and neutropenic fever in 2 patients. One patient had radiation pneumonitis. One patient died with progressive disease and pneumonia after two cycles of topotecan. Conclusions: Adjuvant topotecan was well tolerated. The 30% rate of brain metastases suggests the possibility that topotecan was active in the brain. Overall and progression-free survivals are promising. Additional study of adjuvant topotecan in LD-SCLC patients who do not receive PCI may be warranted. No significant financial relationships to disclose.

Evidence for long-term survival in a sizeable proportion of good performance status (PS) patients (pts) with advanced non-small cell lung cancer (NSCLC)

e19016 Background: Approximately 40% of NSCLC pts present with metastatic disease where treatment is considered palliative. Here we examine whether prolonged survival is possible in a sizeable proportion of NSCLC pts with good PS and stage IV disease particularly given the availability of personalized chemotherapy approaches. Methods: NSCLC pts with stage IV disease and an ECOG PS of 0/1 were prospectively accrued to four phase II clinical trials, at the H. Lee Moffitt Cancer Center and treated with the following regimens; Trial A) carboplatin/gemcitabine first-line followed by docetaxel second-line, Trial B) docetaxel and gefitinib combination therapy in patients aged 70 years or older, Trial C) combination therapy with carboplatin/paclitaxel/atrasentan, Trial D) personalized therapy (PT) based on ERCC1 and RRM1. Pts with low RRM1/low ERCC1 received gemcitabine/carboplatin; low RRM1/high ERCC1, gemcitabine/docetaxel; high RRM1/low ERCC, docetaxel/carboplatin; high RRM1/high ERCC1, vinorelbine/docetaxel. Data were updated as of 10/23/08. Overall survival was estimated using the piecewise exponential survival function which showed a dramatic shift at 29 months. Results: A total number of 181 pts were accrued. The median survival for the entire cohort was 10.5 months improving dramatically to 85.3 months, if alive at 29 months (adjusted P = 0.005). In the entire cohort, 16.7% of pts survived to 29 months compared to 25% of pts in the PT group. For pts who were alive at 29 months, the probabilities of surviving to 48, 60, 72 and 84 months were 79%, 68%, 59% and 51%, respectively. Conclusions: Long term survival is possible in a sizeable proportion of stage IV NSCLC with good PS. Our treatment paradigm should shift from palliation to achieving long term survival. Molecularly-based PT may be one way of achieving this goal. No significant financial relationships to disclose.

Results of 27 years of phase III trials for patients with extensive-disease small-cell lung cancer

e19021 Background: Few studies have formally assessed whether treatment outcomes for patients with extensive-disease small-cell lung cancer (ED-SCLC) enrolled in Phase III trials have improved substantially over the years. This investigation determined the trends in the outcomes for the patients in those trials. Methods: We analyzed trials that were reported between January 1991 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated using linear regression analysis. Results: We identified 55 trials initiated between 1980 and 2006, involving 10,407 patients with 116 chemotherapy arms. The number of randomized patients and the proportions of patients with good performance status (PS) increased with the passage of time. In the 1990s, increasing numbers of studies examined cisplatin-based regimens, especially cisplatin and etoposide (PE) regimens, while decreasing numbers examined cyclophosphamide, doxorubicin, and vincristine-based regimens. A scattergram of the parameters ‘year of trial initiation’ and ‘median survival time’ (MST) indicated that MST increased 0.024 months (0.71 days) per year (P = 0.198). The multiple regression analysis showed no significant survival improvement over the years (regression coefficient for the year of trial initiation = 0.004, P = 0.980). In addition, the use of PE regimens did not prolong survival, whilst the proportion of good PS patients and the assignment of prophylactic cranial irradiation were significantly associated with favorable outcomes. Conclusions: The survival of patients with ED-SCLC enrolled in phase III trials has not improved significantly over the years, suggesting the need for a breakthrough, such as the discovery of novel molecular targets. No significant financial relationships to disclose.

Association de radiothérapie et de chimiothérapie-thérapeutiques ciblées dans les glioblastomes

Despite recent and significant progress, the prognosis of glioblastoma remains extremely poor. Concomitant chemoradiotherapy with temozolomide is now the standard of care for newly diagnosed glioblastoma. This treatment is well-tolerated and results in improvement of overall survival and dramatic increase of long term survivor rate, especially in good performance status patients. Besides, this benefit is particularly marked in patients with MGMT (methylguanine methyltransferase) methylated tumor, suggesting a growing place of molecular markers in pattern of care of such patients. At recurrence, the combination of bevacizumab (anti-VEGF) with irinotecan has shown surprising high response rates in a phase II trial for recurrent malignant gliomas. Many other targeted therapies are currently under investigation, alone or in association, at recurrence or up-front and during radiotherapy. For this reason, in the future a more precise understanding of gliomagenesis is needed for a better molecular stratification of patients.

Phase II trial of S-1 in combination with gemcitabine for chemo-naïve patients with locally advanced or metastatic pancreatic cancer

We performed a phase II study of combination chemotherapy with S-1 plus gemcitabine for treating chemo-naïve patients with unresectable pancreatic cancer to evaluate the efficacy and toxicity. Patients with histologically confirmed unresectable pancreatic cancer were eligible. The treatment consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1 to 14) and gemcitabine (1,250 mg/m(2) on D1 and 8), repeated every 3 weeks. Thirty-two patients were enrolled between March 2005 and December 2007. No complete response was observed and a partial response was observed in 14 patients (44.0%), stable disease in eight patients (25.0%), and progressive disease in eight patients (25.0%). The median time to progression was 4.92 months (95% CI: 4.16-5.67 months), and the median overall survival was 7.89 months (95% CI: 5.96-9.82 months). The survival duration was significantly longer for the patients with a good performance status compared with that of the patients with a poor performance status. The major toxicities were grade 3-4 neutropenia (9, 28.1%), grade 3/4 thrombocytopenia (5, 15.6%), and grade 3 diarrhea (5, 15.6%). The combination chemotherapy of S-1 and gemcitabine showed promising antitumor activity and manageable toxicities, and especially for the good performance status patients with unresectable pancreatic cancer.

How to improve loco-regional control in stages IIIa–b NSCLC?: Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group

Background A combination of chemotherapy and radiotherapy is the treatment base for locally advanced non-small cell lung cancer (NSCLC). However, both loco-regional and distant failure is frequent. Attempts to improve the loco-regional control were made in three separate phase II studies in Swedish University Hospitals, where accelerated radiotherapy or concurrent daily or weekly chemotherapy with conventional radiotherapy were tested. Comparatively good results from these studies lead to this national randomized phase II study, the RAKET-study, where the different concepts were investigated on a wider basis for further phase III studies. Methods Inoperable stage III non-small cell lung cancer patients in good performance status (PS < 2) were equally randomized to either of three arms in eight institutions. All arms started with two cycles of induction chemotherapy: paclitaxel 200 mg/m 2 and carboplatin AUC6. Arm A: a third identical cycle was given concomitant with start of accelerated radiotherapy, 1.7 Gy BID to 64.6 Gy in 4.5 weeks. Arm B consisted of daily concomitant paclitaxel 12 mg/m 2 with conventionally fractionated radiotherapy: 2 Gy to 60 Gy in 6 weeks. Arm C: weekly concomitant paclitaxel 60 mg/m 2 and identical radiotherapy to 60 Gy. Primary endpoint: TTP. Secondary: OS, toxicity, QL and relapse pattern. Results Between June 2002 and May 2005 152 patients were randomized and of them 151 were evaluable: 78 men and 73 women, median age 62 years (43–78), 55% had performance status 0 and 45% PS 1. Thirty-four percent had stage IIIa and 66% IIIb. Histology: adenocarcinoma 48%, squamous cell carcinoma 32% and 20% non-small cell carcinoma. The three arms were well balanced. Toxicity was manageable with 12% grades 3–4 esophagitis, 1% grades 3–4 pneumonitis and there was no clear difference between the arms. The QL data did not differ either. Median time to progression was 9.8 (8.3–12.7) months (8.8, 10.3 and 9.3 months for arms A, B and C, respectively). Median survival was 17.8 (14.4–23.7) months (17.7, 17.7 and 20.6 months for A, B and C, respectively). The 1-, 3- and 5-year overall survival was 63, 31 and 24%. Sixty-nine percent of the patients relapsed with distant metastases initially and 31% had loco-regional tumor progression, without significant differences between treatment arms. Thirty-four percent developed brain metastases. Conclusions Treatment results are quite equal by intensifying the loco-regional treatment either by accelerated fractionated radiotherapy or daily or weekly concomitant chemo-radiotherapy both in terms of survival, toxicity and quality of life. The optimal treatment schedule for patients with locally advanced NSCLC is still to be decided and investigated in future clinical studies. Relapse pattern with distant metastases and especially brain metastases is a great problem and need further research for better therapy options and higher cure rate for this patient group.

Salvage definitive chemo‐radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: Retrospective review

To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival.