Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine.

Background: The modest improvement in median survival of advanced non-small-cell lung cancer (NSCLC) by cisplatin-based chemotherapy has led to the current opinion that clinical benefit for the patient is at least as important an end-point as objective response rate (ORR) or survival. Clinical benefit response was the primary end-point of this prospective randomised trial in symptomatic, advanced stage IIIB/IV NSCLC, comparing single agent gemcitabine (GEM) to cisplatin-based chemotherapy.

Patients And Methods: Patients received either GEM (1000 mg/m2, days 1, 8 and 15) or cisplatin (100 mg/M2, day 1) plus Vindesine (3 mg/m2, days 1 and 15) (PV), both every four weeks.

Gemcitabine plus etoposide in chemonaive extensive disease small-cell lung cancer: a multi-centre phase II study.

Background: Both gemcitabine and etoposide are active in the treatment of small-cell lung cancer (SCLC), and are characterised by mild toxicity profiles. The combination of both drugs was found to be feasible and active in a phase I dose-finding study in solid tumours. Therefore, a phase II trial was initiated to examine the activity and toxicity of this schedule in extensive disease SCLC.

High frequency of cytolytic T lymphocytes directed against a tumor-specific mutated antigen detectable with HLA tetramers in the blood of a lung carcinoma patient with long survival.

We have identified an antigen recognized by autologous CTL on the lung carcinoma cells of a patient who enjoyed a favorable clinical evolution, being alive 10 years after partial resection of the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and encoded by a mutated sequence in the gene coding for malic enzyme, an essential enzyme that converts malate to pyruvate. In the tumor cell line derived from the patient, only the mutated malic enzyme allele is expressed, because of a loss of heterozygosity in the region of chromosome 6 that contains this locus.

A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.

By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2.

Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited-disease small-cell lung cancer: prolonged intrathoracic tumor control and high central nervous system relapse rate. Groupe d'Oncologie-Pneumologie Clinique de l'Université Catholique de Louvain, Brussels and Liège, Belgium.

Background: The role of chemotherapy dose-intensification in small-cell lung cancer (SCLC) remains unclear. This phase I-II study evaluates feasibility and outcome of combination chemotherapy at moderately elevated doses with concomitant thoracic radiotherapy in limited-disease SCLC.

Patients And Methods: Moderately elevated doses of ifosfamide-epirubicin (cycles 1 and 3) and of carboplatin-etoposide (cycles 2 and 4) were given with G-CSF and peripheral blood stem-cell (PBSC) support.

Cutting edge: rapid cloning of tumor-specific CTL suitable for adoptive immunotherapy of melanoma.

Adoptive immunotherapy using CTL has provided some clinical benefit to patients with metastatic melanoma. Use of cloned CTL of known specificity might improve clinical effect, but technical difficulties have limited exploration of this possibility. We have used fluorescence-driven cell sorting to clone tumor-specific CTL after staining with tetrameric MHC class I/peptide complexes.

Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed.

Derivation of tumor-specific cytolytic T-cell clones from two lung cancer patients with long survival.

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively.

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer.

The combination of the limits encountered with current therapies and the increased knowledge of immunology have opened perspectives for the use of immunomodulators in the management of lung cancer patients. Both humoral and cellular immunity are now evaluated in diagnosis and treatment of cancer. Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested with various imaging techniques to improve detection and staging of lung cancer.

[A phase II multicenter study of gemcitabine in non small cell lung cancers].

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle).

Systemic supply to a pulmonary arteriovenous malformation: potential explanation for recurrence.

A pregnant woman presented with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) and a single pulmonary arteriovenous malformation (AVM) that had been embolized 5 years previously. Partly due to pregnancy, recanalization of the aneurysm occurred with subsequent hemoptysis. Despite successful therapeutic reembolization of the afferent pulmonary artery, hemoptysis recurred 5 days later.

A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.

Many human tumor cells have been shown to express antigens that are recognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature of a number of melanoma antigens has been defined recently. Here we describe the characterization of an antigen recognized on a renal cell carcinoma by autologous CTL clones. This antigen is encoded by the HLA-A2 gene present in the tumor cells.

Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study.

Gemcitabine is a novel nucleoside analogue with activity in solid tumours. This study assessed the objective response rate to gemcitabine given weekly intravenously at a dose of 1250 mg/m2 for 3 weeks followed by 1 week of rest (one cycle) in chemonaive patients with inoperable non-small cell lung cancer (NSCLC). 161 patients with NSCLC were recruited from 10 sites in nine countries.

Dermatomyositis and bronchial squamous cell carcinoma: evidence for a true relationship.

The authors report a case of dermatomyositis (D.M) in a 57-year-old man, associated with a squamous cell bronchial carcinoma. The complete resolution of the dermatomyositis after radical resection of the bronchial tumor strongly suggested a paraneoplastic phenomenon.

Bronchioloalveolar carcinoma: computed tomography findings.

The aim of the present study was to investigate the appearance of bronchioloalveolar lung carcinoma on computed tomography (CT) scans, and to determine the frequency of signs suggestive of this diagnosis. CT features of 42 cases with pathologically proven bronchioloalveolar carcinoma were retrospectively analysed for pattern, size, location and secondary signs suggesting the diagnosis. Bronchioloalveolar carcinoma had one of the following patterns: solitary nodule or mass (16), lobar consolidation (10), multilobar consolidations (13) and diffuse nodules (3).

3D spiral CT of the tracheobronchial tree.

Objective: Because of intrinsic limitations of transverse cross-sectional imaging methods, CT sometimes is insufficient for adequate evaluation of complex tracheobronchial anomalies. This article describes a complementary 3D procedure specifically dedicated to the study of the tracheobronchial tree.

Materials And Methods: The procedure combines a specific spiral CT acquisition with 2 or 4 mm collimation, 3D surface rendering of the tracheobronchial aerial content, and double obliquity multiplanar reformats directly planned on the 3D virtual object.

[Spontaneous pneumothorax. Results of pleural talc therapy using thoracoscopy].

The aim of this retrospective study is to evaluate the advantage of thoracoscopy and the efficacy of talcage in the treatment of spontaneous pneumothorax (SP). Two hundred cases have been analyzed with a follow-up of 1 to 8 years after the occurrence of the disorder. The ratio man/woman is 4/1.

Expression of mage genes by non-small-cell lung carcinomas.

Human gene MAGE-I codes for an antigen that is recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). This antigen is potentially useful as a target for cancer immunotherapy because gene MAGE-I is not expressed in any normal tissues except the testis. We tested 46 surgical samples of non-small-cell lung carcinomas and observed MAGE-I expression in 16 of them (35%).

Dose-dependent interleukin-3 stimulation of thrombopoiesis and neutropoiesis in patients with small-cell lung carcinoma before and following chemotherapy: a placebo-controlled randomized phase Ib study.

Purpose: To evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with small-cell lung cancer (SCLC) before and following multiagent antineoplastic therapy in a placebo-controlled, randomized, double-blind study.

Patients And Methods: Twenty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.

Genes coding for tumor antigens recognized by human cytolytic T lymphocytes.

In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone.