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Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]

Inoperable non–small-cell lung cancer has become the domain of combined-modality treatment based on several recent, large, phase III studies. Results of Radiation Therapy Oncology Group (RTOG) phase II studies have

CHICAGO-Systemic chemotherapy would seem to be a reasonable option to reduce the number of deaths from metastatic transitional cell bladder carcinoma. To date, however, systemic neoadjuvant chemotherapy has failed to show an effect on survival, and the jury is still out on the issue of chemotherapy following definitive therapy, said Derek Raghavan, MD, chief of medical oncology, University of Southern California Norris Cancer Center.

Prospects for the multimodality treatment of non–small-cell lung cancer have improved substantially with the demonstration of fairly dramatic results, in terms of 5-year survival, in several phase III trials that employed

The activity and toxicity profiles of carboplatin (Paraplatin) and paclitaxel (Taxol) used as single agents in non–small-cell lung cancer made them logical agents for study in combination therapy. Once preliminary trials

Scientists fear that existing genetic techniques will be misused before the consequences of altering the human blueprint on personal, generational, and societal levels are fully realized. At St. Jude Children’s Research Hospital in Memphis, Tennessee,

Despite growing evidence that patients with advanced non–small-cell lung cancer have improved survival and better symptom control with modern systemic therapy, there is still resistance to the use of chemotherapy because

Combined-modality approaches integrating carboplatin (Paraplatin) and low doses of weekly paclitaxel (Taxol) with thoracic radiation therapy for prolonging survival in patients with locally advanced non–small-cell lung cancer

Single-agent, intratumoral gene therapy that targetsthe p53 gene is well tolerated and shows evidence of antitumor activity in patients with recurrent squamous cell carcinoma of the head and neck, according to the preliminary results of phase II clinical

The article by Drs. Gordon and Vokes provides the reader with a comprehensive overview of the treatment of locally advanced unresectable non–small-cell lung cancer (NSCLC) with chemotherapy and radiation therapy. The authors

PHILADELPHIA-Intranasal delivery of an adenoviral vector containing the murine interleukin-12 (IL-12) gene has been shown to inhibit osteosarcoma lung metastases in mice. IL-12 is a molecule that activates the immune system and has recently been shown to have antiangiogenic activity. “Our hypothesis is that IL-12 interfered with tumor angiogenesis,” Laura L. Worth, MD, PhD, said at the annual meeting of the American Association for Cancer Research.

A pharmaceutical treatment may offer patients an alternative to the usual surgical removal of basal cell carcinomas, according to a presentation at the annual meeting of the American Academy of Dermatology in New Orleans. The results

Stanford researchers have devised a novel approach for delivering a clot-busting gene to blocked leg arteries in animals, effectively restoring blood flow to the damaged vessels, according to a new study presented at the 24th scientific meeting of

Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy

Rituximab (Rituxan) is active in low-grade non-Hodgkin’s lymphoma (NHL), but its efficacy in poor-prognosis intermediate-grade NHL is unknown. To address this issue, we administered rituximab to seven patients with CD20-positive diffuse large cell NHL who had progressive disease despite high-dose therapy and peripheral stem-cell transplantation (PSCT). The median age was 59 years (range, 45-62 years) with ECOG performance status 0-1. Prior to rituximab therapy, all patients had undergone PSCT, with responses of two complete responses (CRs), two partial responses (PRs), one patient with stable disease (SD), and two patients with progressive disease (PD). The CRs lasted 9 and 11 months. Upon relapse or progression of disease, the patients received 4 weekly infusions of rituximab (375 mg/m²).

About 20%-50% of patients with stage IV Hodgkin’s disease may suffer a relapse after initial chemotherapy-induced remission. Consolidative radiotherapy has been used in combination with chemotherapy to reduce relapse at areas of initial bulky disease; however, no survival benefit has been shown in the few randomized studies.

Our studies have shown that unconjugated antibody therapy targeted to the B-cell marker CD20 by the anti-CD20 antibody, C2B8, inhibits the growth of B-cell lymphomas in vitro. We have also demonstrated that B-lymphoma tumor cells can be sensitized to subtoxic doses of therapeutic drugs by the same antibody.

Contamination of the peripheral blood stem-cell (PBSC) graft with lymphoma and residual disease remaining in the patient after high-dose therapy are two potential causes of relapse after autologous transplantation. Using a tumor-specific monoclonal antibody may be one way to purge the stem-cell graft in vivo and increase the efficacy of the preparative regimen. Rituximab (Rituxan) is an IgG1 kappa chimeric mouse/human antibody containing murine light- and heavy-chain variable regions and human gamma 1 heavy-chain and light-chain constant regions. The antibody reacts specifically with the CD20 antigen found on the surface of malignant and normal B-cells.

NAPLES-Nearly one-third of the estimated 144,000 new non-small-cell lung cancer (NSCLC) patients diagnosed in the United States each year are over the age of 65, and these patients often do not have access to the range of treatment options available to younger patients. Platinum-based therapy is often avoided due to concerns about tolerability.

Overexpression of the bcl-2 gene can be detected in approximately 80% to 90% of patients with advanced-stage follicular NHL, as well as in 20% to 30% of those with diffuse large B-cell NHL. A number of studies have attempted to correlate outcome with residual disease using PCR in patients who have achieved a clinical complete response with chemotherapy, antibody treatment, or high-dose therapy with stem-cell support. However, the studies have been inconsistent, and, therefore, the clinical value of such measurements has been limited.

AVENTURA, Florida-Herceptin (trastuzumab) has produced major objective responses in 20% to 25% of patients with previously untreated metastatic breast cancers that overexpressed the HER-2 breast cancer gene. The monoclonal antibody is approved for use as first-line therapy in combination with paclitaxel (Taxol) and as a single agent in second- and third-line therapy.

TORONTO-CD34+ selection of peripheral blood stem cells (PBSCs) significantly reduces tumor cell contamination while providing safe and rapid hematologic recovery for multiple myeloma patients receiving myeloablative therapy, Dr. A.K. Stewart, of Toronto Hospital, reported at ASH.

SAN ANTONIO-In a trial of first-line, single-agent therapy for metastatic breast cancers that overexpress the HER-2 breast cancer gene, Herceptin (trastuzu-mab) resulted in major objective responses in 20% to 25% of patients. The monoclonal antibody is approved for use as first-line therapy in combination with paclitaxel (Taxol) and as a single agent in second- and third-line therapy.

MIAMI BEACH-As more cancer patients undergo allogeneic and autologous peripheral blood stem cell (PBSC) and bone marrow transplants, more long-term complications crop up. Two papers presented at the ASH meeting addressed the late effects of reduced bone density and development of therapy-related leukemia.

WASHINGTON-Walden-ström’s macroglobulinemia is a rare low-grade B-cell lymphoproliferative disorder. Patients with Waldenström’s also often have small lymphocytic lymphoma (SLL). Hyperviscosity in Waldenström’s responds temporarily to plasmapheresis. Alkylator therapy, fludarabine (Fludara), and cladribine (Leustatin) are effective in many cases, but there are no good options for patients refractory to purine analogs.

Rituximab (IDEC-C2B8 [Rituxan]) is a chimeric anti-CD20 monoclonal antibody (MoAb) that was recently approved by the FDA for the treatment of patients with low-grade or follicular B-cell non-Hodgkin’s lymphoma. Its potential efficacy in other B-cell malignancies is currently being explored. This article reviews the mechanisms of action of rituximab, as well as preclinical data and results of the clinical trials that led to its approval. Also discussed are the mechanics of administering rituximab on the recommended weekly ´ 4 outpatient schedule. Finally, the article describes ongoing and planned trials of rituximab in other dosage schedules, in other B-cell neoplasms, and in conjunction with chemotherapy. As the first MoAb to gain FDA approval for the treatment of a malignancy, rituximab signals the beginning of a promising new era in cancer therapy. [ONCOLOGY 12(12):1763-1770, 1998]

SAN DIEGO--The longest follow-up studies to date on dose-intensive therapy with peripheral blood stem cell or bone marrow support in patients with Hodgkin’s disease or non-Hodgkin’s lymphoma (NHL) show some promising results with specific drug regimens.

INDIANAPOLIS--Eli Lilly and Company’s Gemzar (gemcitabine) has received FDA approval for use as first-line treatment of inoperable, locally advanced, or metastatic non-small-cell lung cancer (NSCLC) in combination with cisplatin (Platinol). The agent was previously approved as first-line, single-agent therapy of locally advanced or metastatic pancreatic cancer

It was not until 1995 that a phase III randomized trial demonstrated that autologous stem cell transplants (ASCT) improve the progression-free and overall survival of patients with relapsed refractory diffuse aggressive non-Hodgkin’s lymphoma. Investigators are now focusing on improving the clinical benefit of transplants. The relative contributions made by more intensive preparative regimens, purging, concomitant immunotherapy, and the timing of transplants are under study. Also, as transplant trials shift from relapsed disease to initial therapy, anticipated benefits must be balanced against both short-term and long-term toxicities.[ONCOLOGY 12(Suppl 8):56-62, 1998]

Doctors at the University of Pittsburgh Cancer Institute are exploring a new experimental therapy in which they transfer the tumor-suppressing gene TP53 (alias p53) into patients to reverse tumor progression. University of Pittsburgh clinical