News

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.

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.