News

SAN DIEGO--A therapy for advanced lung cancer patients who have not responded to other treatments is showing promise in studies at M.D. Anderson Cancer Center. In this phase I trial, 18 patients with non-small-cell lung cancer (NSCLC) and missing or defective copies of the tumor-suppressor p53 gene have received injections directly into their tumors of an adenovirus containing the p53 wildtype gene.

Gene therapy for prostate cancer faces hurdles similar to those being encountered for other cancers and nonmalignant processes. The greatest obstacle is the identification of efficient delivery systems, since numerous animal models and cell culture systems have shown potential efficacy when most cells express the introduced genetic material. Early prostate cancers are easily accessible to gene vector introduction, and the predictable metastatic patterns of this cancer may offer additional advantages for gene therapy. This article reviews gene vectors and gene products, as well as ongoing trials of gene therapy that have recently begun in prostate cancer. [ONCOLOGY 11(6):845-856, 1997]

CHICAGO--Cellular tumor bio-markers may be able to identify patients with N1 non-small-cell lung adenocarcin-oma who could achieve better survival and control of metastasis through aggressive adjuvant therapy, Ritsuko Komaki, MD, said at the Radiological Society of North America meeting.

VIENNA--Although the majority of patients with advanced non-small-cell lung cancer (NSCLC) are too ill to tolerate platinum therapy, the more benign safety profile of gemcitabine (Gemzar) is opening up the possibility of palliative chemotherapy for a wider group of NSCLC patients.

Overexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]

NASHVILLE-In 1996, delivery difficulties were the major barrier to breast cancer gene therapy, Jeffrey T. Holt, MD, said at a plenary session of the San Antonio Breast Cancer Symposium.

With the increased use of doxorubicin-based chemotherapy, chemoendocrine therapy, and high-dose chemotherapy with autologous bone marrow transplantation or peripheral blood progenitor-cell reinfusion, the role

ST. PETERSBURG, Russia--High doses of the investigational antiestrogen toremifene (Fareston) proved safe and effective as palliative therapy in patients with advanced renal cell carcinoma, say Dr. Michael Gershanovich and colleagues, of the Professor N. N. Petrov Research Institute of Oncology, St. Petersburg, and Orion Corporation, Turku, Finland.

SAN ANTONIO-Although paclitaxel (Taxol) is still being evaluated as a single agent in advanced breast cancer, to determine optimal dosing and schedule, it is also being studied for use in combination with other cytotoxic agents, as adjuvant therapy in early-stage disease, and as part of high-dose chemotherapy regimens used with stem cell transplant.

In recent years, the treatment of many patients with non-small-cell lung cancer (NSCLC) has evolved into a multidisciplinary effort combining the talents of medical oncologists, radiation oncologists, and thoracic surgeons. Prospective, randomized trials have demonstrated improved survival rates in patients with locally advanced disease who are treated with cisplatin (Platinol)-based induction chemotherapy prior to radiation therapy[1,2] or surgery.[3,4] However, interpretation of these and other studies and application of the findings to the management of an individual patient require a thorough understanding of prognostic factors and staging.

ORLANDO--Fludarabine (Flu-dara) improves response, duration of response, and progression-free survival over standard therapy in previously untreated patients with active B-cell chronic lymphocytic leukemia (CLL), and it should be included in the list of drugs for first-line treatment of this disease, Kanti R. Rai, MD, said at the 38th Annual Meeting of the American Society of Hematology (ASH).

Patients with advanced non-small-cell lung cancer (NSCLC) who are treated with chemotherapy and radiation therapy live longer, on average, than patients treated with radiation therapy alone, according to results of a long-term follow-up study by Robert O. Dillman, md, and colleagues at the Hoag Cancer Center, Newport Beach, California. In the study report appearing in the September 4th issue of the Journal of the National Cancer Institute, the authors recommend that cisplatin (Platinol)-based chemotherapy followed by radiation therapy be considered the current standard treatment for advanced (stage III) disease.

Responding to the need for more efficacious and less toxic treatments for chronic myelogenous leukemia (CML), researchers at the University of Pennsylvania are exploring a novel form of gene therapy. By interfering with the transmission of a crucial message, they hope to prevent malignant cell growth without affecting normal hematopoietic cells.

Rockville, Md --GenVec has begun a phase I study of its in vivo gene-based product, AdgvCD. 10, in 18 patients with liver metastases of colectoral cancer . An advenovirus vector modified to carry the cytosine deaminase gene will be administered directly into the hepatic tumor. The gene expresses an enzyme that converts 5-fluorocytosine,an oral anti-fungal agent , into the potent anticancer agent 5-fluorouracil.. The conversion occurs only at the site of gene expression, the company said.

DNA sequence analysis of the complete p53 tumor-suppressor gene provides predictive information about breast cancer patients' response to therapy, according to a study published in the October 1995 issue of Nature Medicine. The study analyzes the associations between tumor mutations and patient outcome--especially in relation to therapy--using Sequence-Based Diagnosis, (SBD), a new concept for complete DNA sequencing. Although previous studies have examined p53 using various molecular biologic methods, this study represents the first complete sequencing of the p53 gene in a large retrospective study of a population-based cohort. The study also confirms that since mutations are found over the entire coding sequence, some could be missed using traditional DNA analysis protocols.

SAN ANTONIO--Although the literature suggests that peripheral blood stem cell support for hematologic salvage after high-dose chemotherapy is somewhat less expensive than autologous bone marrow transplant (ABMT), the difference is nowhere near the $80,000 disparity found in diagnostic-related group (DRG)-based reimbursement, Philip Bierman, MD, said at a lymphoma symposium sponsored by the University of Texas M.D. Anderson Cancer Center.

MIAMI BEACH--Pretreatment hemoglobin level has been shown to have an independent effect on local control and survival in patients with T1-T2 squamous cell carcinomas of the glottic larynx, Douglas A. Fein, MD, reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO). Based on this finding, it may be advisable to correct anemia in these patients before starting radiation therapy, he said.

New research that is bringing ribozyme therapy closer to clinical trials was presented at the recent meeting of the American

The POpulation HEalth Model (POHEM) lung cancer microsimulation model has provided a useful framework for calculating the cost of managing individual cases of lung cancer in Canada by stage, cell type, and treatment modality, as well as the total economic burden of managing all cases of lung cancer diagnosed in Canada. These data allow an estimation of the overall cost effectiveness of lung cancer therapy. The model also provides a framework for evaluating the cost effectiveness of new therapeutic strategies, such as combined modality therapy for stage III disease or new chemotherapy drugs for stage IV disease. By expressing the cost of lung cancer treatment as cost of life-years gained, such analyses allows useful comparisons of the cost effectiveness of these treatments with those of other costly but accepted medical therapies. [ONCOLOGY 9(Suppl):147-153, 1995]

DNA sequence analysis of the p53 gene may provide information about the response to therapy for breast cancer patients,

MONTREAL, Canada--The centerpiece of efforts to develop gene therapy to treat human immunodeficiency virus (HIV) disease at the University of California, San Diego, has been the use of ribozymes, Flossie Wong-Staal, PhD, said at the 19th International Congress of Chemotherapy.

GAITHERSBURG, Md--Genetic Therapy, Inc. has begun phase I testing of a gene therapy protocol designed to protect patients' blood from the destructive effects of high-dose chemotherapy. The trial, headed by Kenneth H. Cowan, MD, PhD, of the NCI, will include approximately 18 metastatic breast cancer patients being treated at the NIH.

BASLE, Switzerland--Sandoz Ltd. has entered into a merger agreement with Genetic Therapy, Inc (Gaithersburg, Md) with a cash tender offer valued at $295 million. The acquisition "puts Sandoz at the forefront of gene therapy technology," said Daniel Vasella, MD, CEO of Sandoz Pharma.

PARIS, France--Comparison of two sequential Radiation Therapy Oncology Group (RTOG) trials has shown that the addition of cisplatin (Platinol) and etoposide (VePesid) to hyperfractionated radiation therapy significantly boosts survival in patients with inoperable non-small-cell lung cancer (NSCLC), Ritsuko Komaki, MD, reported at the American Radium Society meeting.

WASHINGTON--The U.S. Patent and Trademark Office has awarded a broad patent on gene therapy to the National Institutes of Health. Six years after filing the application, NIH and its licensee, Genetic Therapy, Inc. of Gaithersburg, Maryland, can now use the patent for ex vivo human gene therapy.

GAITHERSBURG, Md--The National Institutes of Health (NIH) has licensed its broad patent covering gene therapy techniques to Genetic Therapy, Inc. The inventors cited on the patent are gene therapy pioneers W. French Anderson, Steven Rosenberg, and Michael Blaese.

Radiation Therapy Oncology Group Study 91-11 offers patients with stage III and IV squamous cell carcinoma of the glottic and supraglottic larynx a chance to save their voice box.

COLLEGEVILLE, Penn--A patient with advanced non-small-cell lung cancer has become the first to receive an injection of a p53/retrovirus gene therapy into existing tumor cells, Introgen Therapeutics, Inc. and RPR Gencell, a division of Rhône-Poulenc Rorer, have announced.

MENLO PARK, Calif--Ansan, Inc., an operating company of Titan Pharmaceuticals, has received FDA approval to start a phase I trial of its butyric acid derivative AN-9 in patients with solid tumors. In preclinical studies, AN-9 demonstrated broad anticancer activity and may have less toxicity than standard chemotherapeutic agents, the company said.

NASHVILLE--Researchers at the National Institutes of Health have seen objective responses in some of the 15 patients treated to date in the first clinical trial of gene therapy in brain tumors, Michael Blaese, MD, said at the scientific subcommittee session on gene therapy at the American Society of Hematology (ASH) meeting.