Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials.

Background: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response.

Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial.

Background: Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT).

Safety, Antitumor Activity, and T-cell Responses in a Dose-Ranging Phase I Trial of the Oncolytic Peptide LTX-315 in Patients with Solid Tumors.

Purpose: LTX-315 is a first-in-class, 9-mer membranolytic peptide that has shown potent immunomodulatory properties in preclinical models. We conducted a phase I dose-escalating study of intratumoral LTX-315 administration in patients with advanced solid tumors.

Patients And Methods: Thirty-nine patients were enrolled, receiving LTX-315 injections into accessible tumors.

Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer.

Unlabelled: Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials.

Survival in Limited Disease Small Cell Lung Cancer According to N3 Lymph Node Involvement.

Background/aim: There are several definitions of limited disease (LD) in small cell lung cancer (SCLC), differing with respect to N3 disease accepted. We analyzed patients from a randomized trial comparing two schedules of thoracic radiotherapy (TRT) in LD SCLC to investigate whether there were survival differences between N3 subcategories (n=144).

Patients And Methods: Patients with a baseline CT scan available were analysed.

Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non-Small Cell Lung Cancer.

Introduction: In this phase 2 study, we evaluated the activity of AUY922 in pretreated patients with stage IV NSCLC.

Methods: Patients with advanced NSCLC were divided into molecularly defined strata based on mutations in the EGFR gene, the ALK receptor tyrosine kinase gene (ALK), the KRAS gene, or the wild type of all three. All patients must have received more than two prior lines of therapy, except for those in a fifth stratum for a less pretreated EGFR cohort (EGFR<2).

Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer.

In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases.

T-helper cell receptors from long-term survivors after telomerase cancer vaccination for use in adoptive cell therapy.

We herein report retargeting of T-helper (Th) cells against the universal cancer antigen telomerase for use in adoptive cell therapy. The redirected Th cells may counter tumor tolerance, transform the inflammatory milieu, and induce epitope spreading and cancer senescence. We have previously conducted a series of trials evaluating vaccination with telomerase peptides.

Randomized phase III PITCAP trial and meta-analysis of induction chemotherapy followed by thoracic irradiation with or without concurrent taxane-based chemotherapy in locally advanced NSCLC.

Background: Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome.

Material And Methods: In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60-61.

Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer.

Background: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort.

Immunological factors influencing clinical outcome in lung cancer patients after telomerase peptide vaccination.

We have previously reported two trials in non-small cell lung cancer (NSCLC) evaluating vaccine therapy with the telomerase peptide GV1001. The studies demonstrated considerable differences in survival among immune responders, highlighting that an immune response is not necessarily beneficial. In the present study, we conducted long-term clinical follow-up and investigated immunological factors hypothesized to influence clinical efficacy.

Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer.

Background: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small cell lung cancer (LD SCLC). Twice daily TRT is well documented, but not universally implemented - probably mainly due to inconvenience and concerns about toxicity. A schedule of three-week hypofractionated TRT is a commonly used alternative.

Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial.

Purpose: We report two clinical trials in non-small cell lung cancer (NSCLC) patients evaluating immune response, toxicity, and clinical outcome after vaccination with the telomerase peptide GV1001: a phase II trial (CTN-2006) in patients vaccinated after chemoradiotherapy and an 8-year update on a previously reported phase I/II trial (CTN-2000).

Experimental Design: CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy × 30) and weekly docetaxel (20 mg/m(2)), followed by GV1001 vaccination. CTN-2000: 26 patients were vaccinated with two telomerase peptides (GV1001 and I540).

Potentially curative radiotherapy for non-small-cell lung cancer in Norway: a population-based study of survival.

Purpose: The efficacy of curative irradiation in the treatment of non-small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach.

Methods And Materials: Cases of non-small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway.

Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer.

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks.

Assessing quality of life in a randomized clinical trial: correcting for missing data.

Background: Health-related quality of life is a topic of current interest. This paper considers a randomized phase III study of radiation therapy with concurrent chemotherapy (docetaxel) versus radiation therapy alone in non-small cell lung cancer, stage III A/B. Longitudinal data on quality of life have been obtained through repeated administration of a multi-item questionnaire (EORTC QLQ-C30) developed by the European Organisation for Research and Treatment of Cancer.

A prospective phase II study: high-dose pemetrexed as second-line chemotherapy in small-cell lung cancer.

Purpose: To investigate the efficacy and tolerability of high-dose pemetrexed as second-line chemotherapy in small cell lung cancer (SCLC).

Patients And Methods: Patients with verified SCLC who had received one prior chemotherapy regimen, aged 18-75 years, WHO Performance Status 0-2, no clinical signs of brain metastases and measurable disease were eligible. Patients received pemetrexed 900 mg/m(2) IV every 3 weeks.

Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy.

Background: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients.

Patients And Methods: The 123 PS 2 patients were compared to 309 PS 0/1 patients regarding survival, quality of life (QOL) and treatment toxicity.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

Background: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC).

Methods: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE).

Bone marrow micrometastases in advanced stage non-small cell lung carcinoma patients.

Background: The clinical relevance of bone marrow micrometastases in non-small cell lung cancer (NSCLC) is undetermined, and the value of such analyses in advanced stage patients has not been assessed previously.

Methods: Immunomagnetic selection with the MOC31 (anti-EpCam) antibody was performed to isolate and detect tumor cells in bone marrow aspirates obtained from 196 patients with NSCLC, and the patients were subjected to follow-up for the assessment of survival. Repeated bone marrow samples, 2-7 samples per patient, were obtained from 13 long-term survivors.

Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy.

Background: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m2 and 100 mg/m2) or weekly regimens (35-40 mg/m2). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m2 docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m2 regimen.

Palliative thoracic radiotherapy in locally advanced non-small cell lung cancer: can quality-of-life assessments help in selection of patients for short- or long-course radiotherapy?

Purpose: Patient-assessed health-related quality-of-life (HRQOL) scores, together with demographic and clinical factors in stage III non-small cell lung cancer (NSCLC) patients, are important prognostic factors for survival and may be helpful in determining thoracic radiotherapy (TRT) strategy.

Methods: In a previously published randomized trial, 301 patients were treated with different palliative radiotherapy schedules, comparing short-term hypofractionated TRT (arm A: 17 Gy/2 fractions [n = 105]) with more protracted TRT (arm B: 42 Gy/15 fractions [n = 104]); arm C: 50 Gy/25 fractions [n = 92]). Baseline HRQOL, demographic, and clinical data were available for all patients.

Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer.

Purpose: A phase I/II study was conducted to investigate the safety, tolerability and clinical response to vaccination with a combination of telomerase peptides GV1001 (hTERT: 611-626) and HR2822 (hTERT: 540-548) in patients with non-small cell lung cancer.

Experimental Design: Twenty-six patients with non-small cell lung cancer received intradermal administrations of either 60 nmole (112 microg) or 300 nmole (560 microg) GV1001 in combination with 60 nM (68.4 microg) HR2822 and granulocyte macrophage-colony stimulating factor.

High sensitivity assays for docetaxel and paclitaxel in plasma using solid-phase extraction and high-performance liquid chromatography with UV detection.

Background: The taxanes paclitaxel and docetaxel have traditionally been used in high doses every third week in the treatment of cancer. Lately there has been a trend towards giving weekly low doses to improve the therapeutic index. This article describes the development of high performance liquid chromatographic (HPLC) methods suitable for monitoring taxane levels in patients, focusing on patients receiving low-dose therapy.

Immediate or delayed radiotherapy in advanced non-small cell lung cancer (NSCLC)? Data from a prospective randomised study.

Background And Purpose: To compare the course of symptoms and health-related quality-of-life (HRQOL) after immediate thoracic radiotherapy (TRT) between symptomatic (S) and non-symptomatic (NS) patients with advanced NSCLC.

Patients And Methods: 407 stage III/IV patients were initially treated with immediate TRT within a randomised phase III trial comparing different fractionation schedules. At inclusion, patients were prospectively stratified according to presence (S) or absence (NS) of tumour-related chest/airway symptoms to facilitate comparison between these groups.