News

A number of molecularly targeted agents directed at critical pathways involved in cell survival and cell proliferation have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while diminishing acute and long-term toxic effects. Systematic evaluations of agents such as these are essential if continuing improvements in outcome are to be achieved in children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these agents in pediatric populations

BETHESDA, Maryland-A long-term study to determine which of two common strategies is better for treating HIV-infected individuals was initiated in January, as 21 US centers and several Australian sites began enrolling the first 1,000 patients. Participants in the SMART trial (Strategies for Management of Anti-Retroviral Therapies) are randomized to receive immediate, aggressive antiretroviral therapy ("hit-hard-early") or no HIV drugs until CD4+ T-cell counts fall below 250 cells/µL ("go-slow").

NEW YORK-In patients with metastatic cutaneous melanoma who have already failed or are refractory to standard treatment, Allovectin-7, a targeted gene therapy using a nonviral delivery system, can induce both local and systemic responses in tumors injected weekly, results of a multicenter phase II study suggest.

Front-line treatment for previously untreated follicular B-cell lymphoma with the iodine-131-labeled anti-CD20 antibody tositumomab (Bexxar) has been reported to result in a 97% response rate and a 74% complete response rate. Although the median duration of response has not yet been reached with a median follow-up of 2.7 years, concerns have been raised over the tolerability of salvage treatments upon relapse of disease. We have reviewed the clinical course of the 28 patients that have relapsed among the original group of 76 patients treated with tositumomab/iodine-131 tositumomab as front-line therapy.

There have been significant advances in our understanding of the biology of acute myelogenous leukemia (AML), and to a lesser extent, in its treatment. Dr. Estey has provided an excellent overview of the current state of the clinical management of the disease. He has described both the standard therapeutic approaches, including allogeneic hematopoietic stem cell transplantation, as well as the role of investigational therapy. The present state of clinical research in AML is reviewed in some detail in the context of the broad clinical investigation of the disease at the M. D. Anderson Cancer Center. Dr. Estey makes a strong argument for the early consideration of investigational therapy, focusing on patients for whom "standard" therapy is demonstrably inadequate.

SAN ANTONIO-A retrospective study presented at the 24th Annual San Antonio Breast Cancer Symposium (abstract 18) has shown that breast cancer patients selected for treatment with trastuzumab (Herceptin) combination therapy on the basis of HER-2 gene amplification by fluorescent in situ hybridization (FISH) may have improved clinical benefits.

MIAMI BEACH-Histone deacetylase (HDAC) inhibitors have emerged as promising new candidates in T-cell lymphoma therapy. Phase I data reported by National Cancer Institute (NCI) investigators showed responses in all patients treated with

The search for effective postoperative adjuvant therapy for patients with resected non-small-cell lung cancer (NSCLC) has been spurred by a high rate of failure after definitive surgery. Except for patients with resected T1, N0, M0 lesions, failure rates exceed 30%. Widespread application of adjuvant therapy has been reined in by a disappointing lack of effectiveness in this setting.

CHICAGO-The degree of oxygenation of malignancies in the neck may indicate which patients with squamous cell carcinoma should receive adjuvant therapy, according to a study conducted at Duke University Medical Center.

SILVER SPRING, Maryland-The FDA’s Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended that the agency amend the labeling of Herceptin (trastuzumab, Genentech) to include a new gene-detection test to identify women with metastatic breast cancer who are likely to benefit from the therapy. The 16-to-0 vote backed adding the PathVysion HER-2 DNA Probe Kit to the labeling. The kit is made by Vysis, Inc., now owned by Abbott Laboratories.

Gainesville, FL-Scientists seeking to use gene therapy to reverse a form of inherited blindness have won a $9.8-million grant from the National Institutes of Health (NIH).

Efforts at preventing and treating fungal infection in hematopoietic stem cell transplant (HSCT) recipients must take into account the types of infections likely to be encountered during the different risk periods in hosts with different underlying risks. Given the emergence of molds as prevalent pathogens and the long duration of risk in allogeneic HSCT recipients, optimal antifungal prophylaxis would consist of treatment that can be given over a prolonged period and that would provide both anti-Candida and anti-Aspergillus activity. Optimal empiric therapy would consist of a broad-spectrum agent in the absence of more sensitive and specific methods for microbial diagnosis. Fluconazole (Diflucan) is currently the standard prophylactic agent for candidiasis, although mold-active agents and alternative strategies for polyene administration are being investigated. The gold standard for empiric therapy is currently a polyene antifungal, yet an increased appreciation for amphotericin B-resistant yeasts and molds, and less toxic mold-active alternatives, might lead to the use of other compounds in the future. The recent development of multiple alternatives emphasizes our need to establish treatment algorithms that consider both the likely pathogens and potential toxicities. [ONCOLOGY 15(Suppl 9):15-19, 2001]

WASHINGTON-Combining gene therapy with radiotherapy may provide a useful approach to combating human esophageal cancers, said Vinay Kumar Gupta, MD, of the University of Chicago Medical School, at the 54th Annual Cancer Symposium of the Society of Surgical Oncology.

SAN FRANCISCO-Platinum-based chemotherapy with either gemcitabine (Gemzar) or paclitaxel (Taxol) caused fewer terminations of therapy for progressive disease or adverse events than the reference regimen of platinum with vinorelbine (Navelbine) in advanced non-small-cell lung cancer (NSCLC).

Advances in molecular virology and biotechnology have led to the engineering of vectors that can efficiently transfer genes to target cells. Gene therapy strategies were developed along two lines: Cytotoxic approaches

HOUSTON-‘‘We appear to be approaching a ceiling for benefits of cytotoxic chemotherapy in advanced non-small-cell lung cancer (NSCLC). All recent randomized studies have had similar results, and there has been no clear efficacy benefit from nonplatinum combinations or triplets. Certainly for advanced disease and even for early disease, where metastases kill most patients, a paradigm shift is needed, and that shift will probably be to targeted therapy that works against specific biologic pathways," said Roy S. Herbst, MD, PhD. Dr. Herbst is assistant professor of medicine and chief of the Section of Thoracic Oncology at the University of Texas M.D. Anderson Cancer Center in Houston, Texas.

CHICAGO-Amifostine (Ethyol) has a number of effects on transcription factors and may also mimic antitumor gene therapy by upregulating expression of manganese superoxide dismutase (MnSOD), according to David J. Grdina, MBA, PhD, professor of radiation and cellular oncology at the University of Chicago.

BETHESDA, Md-Enrollment has begun in a trial of Neovastat (Aeterna Laboratories), also known as AE-941, to test the Canadian-produced shark cartilage extract in patients with unresectable stages IIIA and IIIB non-small-cell lung cancer (NSCLC) who are undergoing induction chemotherapy and radiation therapy.

SAN FRANCISCO-Used with concurrent radiation therapy after induction chemotherapy, an investigational agent that decreases hemoglobin’s oxygen-binding affinity produced good response rates and favorable projected survival rates in patients with unresectable non-small-cell lung cancer (NSCLC).

SAN FRANCISCO-Amifostine (Ethyol) reduced acute pneumonitis and severe esophagitis while significantly increasing the complete response rate in patients receiving chemoradiation for inoperable stage II or III non-small-cell lung cancer (NSCLC) during a randomized phase III study. Hypotension was significantly more frequent among those receiving amifostine, although only one patient discontinued therapy because of a hypotensive episode.

MONTVILLE, NJ-The FDA has approved Campath (alemtuzumab) humanized monoclonal antibody for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have been treated with alkylating agents and have failed fludarabine (Fludara) therapy. Campath was developed by M&I Partners, a 50-50 joint venture of Millennium Pharmaceuticals, Inc. and ILEX Oncology, Inc. The agent will be marketed and distributed in the United States by Berlex Laboratories, Inc.

WASHINGTON-Imiquimod (Aldara), an immune response modifier used to treat genital warts, provided effective therapy for both actinic keratosis and primary superficial basal cell carcinoma in pilot studies presented at the 59th Annual Meeting of the American Academy of Dermatology.

NEW ORLEANS-A protein-based compound called BL22 produced complete remissions in patients with hairy cell leukemia resistant to standard therapy with purine analogs. Results of the phase I trial were reported at the 92nd Annual Meeting of the American Association for Cancer Research (AACR).

VENICE, Italy-Adjuvant therapy with the investigational vaccine Melacine helps prevent relapses in patients with stage IIA melanoma, investigators from the Southwest Oncology Group (SWOG) 9035 Study Group announced at the Fifth World Conference on Melanoma. Mela-cine, being developed by Corixa (Seattle), consists of a mixture of allogeneic melanoma cell lysates plus an immunologic adjuvant (Detox).

About 50,000 hematopoietic stem cell transplantations are performed yearly, primarily for malignancies. Use of this therapy increased dramatically over the past 30 years due to its proven and potential efficacy in diverse

NEW YORK-Median survival has pushed past 18 months in a trial of concurrent low-dose gemcitabine (Gemzar) and radiation therapy in highly selected patients with stage III non-small-cell lung cancer (NSCLC), according to a report at the Chemotherapy Foundation Symposium XVIII.

Gemcitabine has demonstrated activity in a broad range of solid tumors with good tolerance. In combined modality therapy, gemcitabine has achieved response rates ranging between 30% and 60% in patients with non-small-cell

As the chemotherapy horizons have expanded in colorectal cancer with development of oxaliplatin (Eloxatin) and irinotecan (CPT-11, Camptosar), so too have our approaches to therapy. Numerous immunotherapy and gene

Lamont et al have presented a very clear and concise review of current gene therapy strategies in the management of squamous cell carcinoma of the head and neck. While the presentation highlighted the most important work to date in this expanding field, it also made reference to some controversies and challenges that we are now facing. With this in mind, I would like to expand on and clarify several points raised by the authors.

Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials. [ONCOLOGY 15(3):303-314, 2001]