Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study.

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m(2), day 1), or regimen B, cisplatin (100 mg/m(2), day 1) plus vinorelbine (25 mg/m(2), days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 x 10(12) particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.

Imaging of intra- and extraabdominal desmoid tumors.

Desmoid tumors are characterized by proliferation of fibroblastic cells that arise from the fascia or aponeurosis of muscle. They are most commonly found in the abdomen of adults, arising from the anterior abdominal wall, mesentery, or retroperitoneum. At sonography, desmoids have variable echogenicity, with smooth, well-defined margins. On contrast-enhanced computed tomographic scans, the tumors are generally high attenuation (relative to muscle) and have either ill- or well-defined margins. At magnetic resonance imaging, desmoids have low signal intensity relative to muscle on T1-weighted images and variable signal intensity on T2-weighted images. There are no specific imaging features to distinguish desmoid tumors from other solid masses. The diagnosis of desmoid tumor should be considered in patients with an abdominal mass, a history of abdominal surgery or injury, or Gardner syndrome.

Is adjuvant treatment with vinblastine effective in reducing the occurrence of distant metastasis in limited squamous cell lung cancer? A randomized study.

In order to study the usefulness of treatment with vinblastine (VLB) in the prevention of cancer metastasis in squamous cell lung cancer, 50 patients with locoregional disease were randomized to receive either locoregional RT alone (group A) or a weekly intravenous bolus injection of VLB (6 mg/m2) concurrently with and after locoregional radiotherapy (RT) (55 Gy in 6 weeks) until the appearance of metastases (group B). Neither the incidence of death with metastases, metastasis-free survival (MFS) nor overall survival (S) were significantly affected by treatment with the drug. However, due to the limited number of patients in each group, the power of the statistical test was such to allow only the detection of differences in MFS and S to or more than 80 per cent at the P = 0.05 level. Local tumor response was significantly superior in group B (P less than 0.05). Acute toxicity (dysphagia, myelosuppression) during RT was significantly worse in group B. During long-term therapy with VLB, mild polyneuropathy developed in the majority of patients in group B. Furthermore, seven patients discontinued treatment with VLB during maintenance due to compliance (4) and excessive neurotoxicity (3). This treatment schedule with VLB is not recommended for patients with locoregional squamous cell lung cancer as significant toxicity is present during and after RT and significant increase in MFS and S is lacking. Because of an apparent increase in local response, the combination of VLB and RT merits further investigation in those tumors where local tumor control is crucial.

Idiopathic familial hemochromatosis: limited disease extent with prolonged survival and arthritis.

Three siblings with idiopathic hemochromatosis are presented. They are remarkable because of the particularly benign disease and absence of typical HLA phenotype in the index case. In only one of the patients is the glucose tolerance disturbed. This case also has an HLA A3 phenotype. A typical hemochromatosis arthropathy is described in two patients. Following venesection a subjective improvement of the arthritis was reported by one patient.

Lower motor neuron disease in a patient with Hodgkin's disease treated with radiotherapy.

A case of lower motor neuron disease after extended field irradiation for cervical stage IA nodular sclerosing Hodgkin's disease is reported. Recurrence of Hodgkin's disease is excluded and other diagnostic possibilities are discussed. We compared this case with twenty-four similar cases reported in the literature after irradiation of the spinal cord for Hodgkin's disease or other neoplasms. Special features included the relatively advanced age of the patient, the long latency period, a premonitory CK-rise and reversibility. The entity is considered to be a very rare and relatively benign complication of spinal cord irradiation important to recognize as an entity in order to avoid extensive reevaluation.