Philadelphia-Gene therapy has successfully restored the visual function of blind dogs with a rare congenital retinal disease, according to early research results. This breakthrough holds implications for the treat- ment of several human retinal degenerative diseases within the next several years.
PHILADELPHIA-T-cell depletion had no clear advantage over immunosuppressive drug therapy in patients receiving a matched, unrelated donor bone marrow transplant, John E. Wagner, MD, reported at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 274).
Non–small-cell lung cancer (NSCLC) accounts for approximately80% of all lung tumors. Patients diagnosed with early-stage diseasegenerally undergo surgery, but up to 50% develop local or distantrecurrences. The benefit of chemotherapy in this disease is modest, butnew drugs and combined strategies offer hope of improved survivalrates. Because the disease recurs outside the chest in 70% of cases, oneof the foremost goals of therapy is to prevent distant dissemination. Tothis end, chemotherapy may be administered preoperatively or afterresection of the tumor. The first part of this article, which concludesnext month, will address adjuvant and neoadjuvant chemotherapy inearly-stage non–small-cell lung cancer.
Bolaños-Meade et al provide aconcise review of tandemtransplantation for patientswith multiple myeloma. High-dosechemotherapy with autologous stemcell support has been shown to improveresponse rates, event-free survival,and overall survival overconventional chemotherapy in a majorrandomized clinical trial-the IntergroupeFrançais du Myélome(IFM)-90 trial.[1] This procedure isnow accepted as the standard of carefor newly diagnosed myeloma patientsyounger than age 70 years. However,the same study demonstrated the needto improve upon single autografts, asthe overall survival rate at 7 years inthe transplant group was only 43%.Conceptual Basis ofTandem AutograftsUsing tandem transplants, investigatorshave aimed to improve outcomesby incrementally achievinghigher complete response rates withrepeated cycles of high-dose therapyrequiring stem cell support. With theirTotal Therapy protocol-a series ofnon–cross-resistant chemotherapyregimens culminating in tandemtransplantation-researchers from theArkansas Cancer Research Centershowed that the complete responserate increased from 26% to 41%following the first and second transplant,respectively.[2] On multivariateanalysis, complete response wasa significant prognostic factor forimproved outcome.
The management of germ cell tumors has advanced dramatically,with cure rates approaching 90% to 95%. Treatment of stage I/Aseminomas generally includes orchiectomy and adjuvant radiotherapy.Treatment of stage I/A nonseminomatous germ cell tumors involvesorchiectomy followed by retroperitoneal lymph node dissection oractive surveillance. One of the major advances has been the introductionof cisplatin-based chemotherapy for metastatic disease and thedevelopment of a system of risk attribution. The logical managementof any patient with curable disease is to provide curative therapy andthen follow the patient in a structured manner, to diagnose and treatany complications in a timely manner.
HOUSTON-Introgen Therapeutics, Inc. has published data from its phase II study combining Advexin, an adenoviral vector containing the p53 tumor-suppressor gene, with radiation therapy in patients with nonmetastatic non-small-cell lung cancer (NSCLC) (Clinical Cancer Research, January 2003). The patients were ineligible to receive surgery or combination therapy with radiation and chemotherapy.
PHILADELPHIA-Remissions induced by gemtuzumab ozogamicin (Mylotarg) monotherapy in patients with first-relapse acute myeloid leukemia (AML) can be prolonged with subsequent therapy. Allogeneic hematopoietic stem cell transplant was particularly effective and even produced some long-term remissions in patients who did not respond to gemtuzumab, Eric Sievers, MD, reported at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 327).
BETHESDA, Maryland-Cell signaling pathways offer many potential targets for antitumor therapies, but hitting those targets is proving more difficult than researchers had anticipated, according to John J. Wright, MD, PhD. He is senior clinical investigator, Investigational Drug Branch, Cancer Therapy Evaluation Program, at the National Cancer Institute in Bethesda, Maryland.
Champlin and colleagues haveelegantly summarized the conceptof nonmyeloablativestem cell transplantation (NST),stressing the importance of this newlyemerging procedure for the treatmentof patients with life-threateningmalignant hematologic and nonhematologicdiseases. This review doesnot include a description of the safetyand efficacy of NST for the treatmentof many life-threateningnonmalignant diseases for which noalternative therapy exists. This categoryencompasses a long list of geneticdisorders, diseases caused by adeficiency of stem cell products, andsyndromes associated with immunedeficiency. However, discussion ofthese illnesses is beyond the scopeof this review, which focuses oncancer.
BRIDGEWATER, New Jersey-The US Food and Drug Administration (FDA) has approved Taxotere (docetaxel, Aventis) as first-line therapy, in combination with cisplatin (Platinol), in patients with unresectable, locally advanced or metastatic non-small-cell lung cancer (NSCLC).
During the 1990s, perhaps no other therapy for women with breast cancer was more controversial than high-dose chemotherapy with autologous bone marrow and/or peripheral stem cell support. With encouraging results from late phase I and early phase II trials in the early to mid-1990s, high-dose chemotherapy was promoted by its many enthusiastic proponents as a potentially great leap forward for women with high-risk, node-positive or metastatic disease.
Interleukin-2 (IL-2, Proleukin) is one of the most effective agents in the treatment of metastatic renal cell carcinoma and metastatic melanoma. High-dose IL-2 therapy produces overall response rates of 15% to 20%;
WASHINGTON-Donna Przepiorka, MD, PhD, formerly of the Baylor College of Medicine and now at the University of Tennessee, Memphis, has become chair of the Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC). She replaces Stacy Nerenstone, MD, of Hartford Hospital in Connecticut, whose term expired. Dr. Przepiorka’s research has focused largely on transplantation immunobiol-ogy and she has a background in cellular and gene therapy. Her term as committee chair will end on June 30, 2004.
BERKELEY HEIGHTS, New Jersey-Genta Incorporated has initiated a new clinical trial with its lead anticancer drug Genasense in patients with multiple myeloma. The study will assess the safety and efficacy of Gena-sense in combination with thalidomide (Thalomid) and dexamethasone in patients who have failed standard therapy. The trial will be conducted at the University of Maryland and is sponsored by the NCI pursuant to Genta’s Cooperation Research and Development Agreement (CRADA). Genasense works by inhibiting the production of Bcl-2, a protein made by cancer cells that blocks chemotherapy-induced cell death. Genasense may enhance the effectiveness of current anticancer treatments, Genta said in a news release.
Evry, France-Neurotech will refocus its efforts on ophthalmic technologies, halting research and development activities in the fields of neuroscience and cell therapy.
n ROCKVILLE, Maryland-The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 3 that phase II results of AstraZeneca Pharmaceuticals’ EGFR tyrosine kinase inhibitor Iressa (ZD1839, gefitinib) as third-line therapy for advanced non-small-cell lung cancer (NSCLC) were "reasonably likely to predict clinical benefit." The FDA considers this a recommendation for accelerated approval. Look for a complete report of the ODAC decision and a review of the phase II trials of Iressa in NSCLC in next month’s issue of ONI.
Although treatment of advanced non-small-cell lung cancer has been improved with the availability of such new agents as the taxanes, topoisomerase inhibitors, vinorelbine (Navelbine), and gemcitabine (Gemzar), platinum-
Lung cancer is the leading cause of cancer-related death in the United States. There was rapid progress in the treatment of lung cancer during past decades, but local control and survival rates are still poor.
Lung cancer remains the primary cause of cancer-related death in both men and women in the United States. Chemotherapy has been shown to provide a survival benefit in patients with advanced non-small-cell lung cancer (NSCLC), and current regimens have produced median survivals of approximately 8 months and 1-year survival rates of 30% to 35% in patients with stage IIIB and IV disease. Nevertheless, there remains room for improvement. Irinotecan (CPT-11, Camptosar) has demonstrated efficacy in the treatment of small-cell lung cancer (SCLC). It also appears to have promising activity in advanced NSCLC, producing overall response rates of up to 32%. Combinations of irinotecan and cisplatin or carboplatin (Paraplatin) have resulted in overall response rates of 25% to 56% in phase II and III studies in patients with advanced disease, with median survivals ranging from 9 to 13 months and 1-year survival rates of 33% to 58%. Current irinotecan-based doublet and triplet regimens appear to produce promising response rates with manageable toxicities. In addition, irinotecan has demonstrated potential as a radiosensitizing agent and is currently being evaluated in several trials of combined-modality therapy in patients with locally advanced NSCLC. Early trials of irinotecan in combination with cisplatin or carboplatin along with radiation therapy have reported overall response rates of 60% to 67%. The approach appears to have potential and warrants further study. [ONCOLOGY 16:1153-1168, 2002]
ORLANDO, Florida-Although a combination of paclitaxel, carboplatin (Paraplatin), and thoracic radiation therapy is commonly used to treat patients with locally advanced non-small-cell lung cancer (NSCLC), the optimal sequencing of these
PHILADELPHIA-"Do not exclude the fit elderly from combined modality therapy for locally advanced non-small-cell lung cancer (NSCLC)," Corey. J. Langer, MD, of Fox Chase Cancer Center, reported in his poster presentation (ASCO
ORLANDO-Preliminary results of a French study show improved event-free survival for patients with indolent non-Hodgkin’s lymphoma (NHL) who received high-dose chemotherapy with purged autologous stem cell transplantation as first-line therapy, compared with conventional standard therapy.
ORLANDO-Patients with locally advanced, un1resectable, non-small-cell lung cancer (NSCLC) who received the radiation enhancer RSR13 (efaproxiral) along with thoracic radiation therapy (RT) had a median survival of more than 20
In less than a decade, docetaxel (Taxotere) has progressed from initial studies in anthracycline-refractory metastatic breast cancer to several large, phase III randomized trials evaluating its efficacy as adjuvant, neoadjuvant, and first-line therapy for metastatic breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer. In other tumor types, including prostate, head and neck, gastric, and bladder cancer, ongoing phase III trials are comparing docetaxel-containing regimens to previously established regimens. For the seven tumor types reviewed in this supplement, phase III study information for docetaxel or docetaxel-based combinations are presented. Impressive results have been consistently demonstrated in the trials reported to date.
Docetaxel (Taxotere) has shown activity both as a single-agent and in combination with multiple other cytotoxic agents in the front-line therapy of advanced, metastatic non-small-cell lung cancer (NSCLC). A randomized, phase III trial demonstrated a survival advantage for docetaxel over best supportive care in the front-line setting, with docetaxel achieving a 2-year survival of 12% vs 0% for best supportive care. Combinations of docetaxel with the platinum agents have been the most extensively studied in the front-line setting and have produced notably high response rates and encouraging median survivals.
ORLANDO-A gene-profiling chip might help identify children with acute lymphoblastic leukemia (ALL) who are at low risk of relapse and could be spared intensive therapy, or who are at high risk for treatment-induced acute myeloid leukemia (AML) and should not be treated with topoisomerase II inhibitors.
LOS ANGELES-Progress in treating cancer-related anemia has accelerated in the almost 20 years since the human erythropoietin gene was cloned. That was in 1983. Ten years later, the Food and Drug Administration approved epoetin alfa (Epogen, Procrit) for transfusion-preventing treatment of patients with anemia-complicating therapy.
The 5-year survival of patients with locally advanced squamous cell cancers of the head and neck is still less than 30%. Treatment of these cancers involves significant functional impairment, diminished quality of life, and considerable time and expense. Local recurrence and distant metastases are still fairly common, and the development of second primary cancers has a significant impact on survival in patients with initial early-stage disease. Despite the success of combination chemoradiation in locally advanced head and neck cancers, these facts stress the need for improved treatment of this disease.
Philadelphia-Much progress has been made in the development of gene therapies for retinal dystrophies during the last decade. Albert Maguire, MD
Dr. Armitage presents a succinct and thorough review of the role of mitoxantrone (Novantrone) in patients with non-Hodgkin’s lymphoma (NHL). He begins by emphasizing the importance of accurate diagnosis as described in the World Health Organization classification which evolved from the Revised European American Lymphoma classification. Both of these present day classifications are based on the immunologic principles separating lymphomas into B- and T-cell disorders developed in the 1970s by Lennert, Lukes, and Collins.[1,2] His review addresses multiple issues in mitoxantrone therapy, including dose intensity, cardiotoxicity, combination therapy with nucleoside analogs in low-grade lymphomas, the impact of rituximab (Rituxan), therapy for acquired immunodeficiency syndrome (AIDS)-related lymphoma, and the role of high-dose mitoxantrone as part of a preparative regimen for autologous transplants.
