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SAN FRANCISCO-Patients with inoperable non-small-cell lung cancer (NSCLC) who receive 20 Gy of radiation therapy in five fractions achieved slightly superior palliation of thoracic symptoms than those receiving a single 10-Gy dose, according to a study presented at the 43rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 30). An unexpected finding was that patients receiving the five-fraction therapy survived significantly longer, the study authors said.

Dr. Alan Sandler’s sweeping review of the role of irinotecan (CPT-11, Camptosar) in the treatment of small-cell lung cancer (SCLC) leaves few stones unturned. Some perspective, however, is necessary. To date, with the exception of the Japan Clinical Oncology Group trial, which demonstrated the superiority of irinotecan in combination with cisplatin compared to standard therapy with etoposide and cisplatin, no other new platinum agent combination has proven superior to standard therapy in the treatment of extensive SCLC.[1] The Noda study, published recently in the New England Journal of Medicine, has sparked considerable interest and anticipation in the medical oncology community.

A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for 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 and other agents in pediatric populations.

Yttrium-90 ibritumomab tiuxetan (Zevalin) has been shown to be an effective and well-tolerated therapy for patients with relapsed B-cell non-Hodgkin’s lymphoma (NHL), with a response rate significantly higher than that seen with rituximab (Rituxan).

Increasing data suggest that rituximab may have activity in a variety of uncommon B-cell malignancies. Although earlier preliminary data suggested a high response rate in hairy cell leukemia (HCL) (Thomas et al: Blood 94:705a[abstract 3116], 1999), the complete response rate of 20% in patients who had previously failed cladribine (Leustatin) therapy reported by Nieva et al was considered disappointing (abstract #1535). A more promising approach to patients with refractory HCL is the BL-22 immunotoxin, in which anti-CD22 is linked to a Pseudomonas exotoxin (Kreitman et al: N Engl J Med 345:241-247, 2001). Of 16 patients treated on a phase I study who had failed at least one purine analog, 13 responded, including 11 complete remissions. At a median of 16 months, only three complete responders relapsed and these were successfully reinduced.

Tositumomab/iodine-131 tositumomab (Bexxar) is a novel active agent against CD20-positive lymphoma. There is a paucity of data examining the tolerance and outcome of hematopoietic stem cell transplantation (HSCT) for relapse after tositumomab/iodine-131 tositumomab.

ORLANDO-High-dose therapy with stem cell support improves event-free survival in patients with mantle cell lymphoma when performed in first remission, according to results of a European Intergroup study presented at the 41st Annual Meeting of the American Society of Hematology (abstract 3572).

Rituximab (Rituxan) has shown high activity in relapsed follicular lymphomas when given alone, and phase II studies indicate that its addition to chemotherapy may further improve response rates substantially. Because prospective randomized studies have not been available so far, the German Low Grade Study Group (GLSG) started a multicenter national trial in patients with relapsed or refractory follicular cell lymphoma (FCL) or mantle cell lymphoma (MCL). As patients were treated for first-line therapy with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), the FCM (fludarabine [Fludara], cyclophosphamide, mitoxantrone [Novantrone]) combination was chosen for salvage chemotherapy.

ORLANDO-Adding rituximab (Rituxan) to paclitaxel (Taxol)/topotecan (Hycamtin) salvage therapy raises response rates by about 25%, more than triples complete response rates, and is effective in both primary refractory and relapsed aggressive B-cell lymphomas.

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.