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ONCOLOGY Vol 13 No 3

Dr. Natale Cascinelli, president of the World Health Organization (WHO) Melanoma Program, declared intraoperative lymphatic mapping to be the standard of care for melanoma. He made this statement during his presentation of the abstract, “An Overview on Sentinel Lymph Node Dissection” at the 9th International Congress on Anti-Cancer Treatments in Paris.

A 60-patient phase II study was conducted to determine the safety and efficacy of retreatment with the anti-CD20 monoclonal antibody (MoAb) rituximab (Rituxan) in patients with low-grade or follicular non-Hodgkin’s lymphoma (NHL). Patients were relapsed or refractory to prior chemotherapy but had previously responded to rituximab. Upon progression of disease, patients received IV infusions of rituximab at 375 mg/m² weekly × 4. Patient characteristics were 55% males with medians of: age, 56 years; three prior therapies; 14.2 months since last treatment; and 4.7 years since diagnosis.

Elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine tartrate (Navelbine) injection enjoy improved survival over those receiving best supportive care, according to a study published in the February issue of the Journal of the National Cancer Institute.

The role of allogeneic bone marrow transplant (BMT) as a treatment for advanced non-Hodgkin’s lymphoma (NHL) has not been established. Historical limitations tothis approach have included the relatively advanced age of these patients, as well as their extensive treatment prior to BMT. Accordingly, only limited data have been reported about overall and/or disease-free survival in these patients. Depletion of T-cells offers the potential for older patients to undergo allogeneic BMT by reducing complications related to graft-vs-host disease (GVHD), but whether the graft-vs-lymphoma effect would be correspondingly reduced is unknown.

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.

Campath-1H is a humanized anti-CD52 monoclonal antibody (MoAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of Campath-1H in patients with low-grade NHL. Fifty patients with advanced, heavily pretreated, low-grade NHL were treated with Campath-1H (30 mg administered as a 2-hour intravenous (IV) infusion 3 times weekly for up to 12 weeks).

Protease inhibitors, routinely used to treat the human immunodeficiency virus (HIV) in the United States, are highly effective against the subtype C viral strain thought to be most prevalent worldwide, report Stanford researchers.

Waldenström’s macroglobulinemia is a rare, low-grade lymphoproliferative disorder for which few therapies are effective. Although patients with Waldenström’s macroglobulinemia often are reported with cases of small lymphocytic lymphoma, this disease has characteristic lymphoplasmacytic histology, bright CD20 expression, and IgM paraproteinemia. Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody that produces a 50% response rate in previously treated low-grade lymphoma, but has no previously described efficacy in the Waldenström’s macroglobulinemia subtype. We report 7 patients with Waldenström’s macroglobulinemia treated on clinical trials performed by IDEC Pharmaceuticals (N = 6) or at our institution (N = 1). Characteristics of these patients included a median age of 60 years (range, 50-75 years) with 5 being female. All patients were symptomatic, with a median performance status of 1 (range, 1-3), with all having measurable disease independent of paraproteinemia.

Several published reports have suggested that although there is a lesser relapse rate for allogeneic bone marrow transplantation (BMT) compared to autologous BMT in patients with low-grade lymphoma, no survival advantage was evident because of higher toxicity associated with allogeneic BMT. To address this issue, we compared outcome in 38 patients with low-grade lymphoma who received allogeneic BMT to 72 patients who underwent autologous BMT at our institution.

Combination chemotherapy, such as CHOP (cyclophosphamide, doxorubicin HCl, Oncovin, and prednisone), or purine analogs, such as fludarabine (Fludara), are commonly used in the treatment of alkylating agent–resistant, relapsed, low-grade B-cell non-Hodgkin’s lymphoma (NHL). Response rates of around 50% are seen, with median remission duration of 6 to 9 months.

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.

Apanel that included top oncologists at some of the nation’s premier cancer centers criticized the National Cancer Institute(NCI) for not looking behind statistics showing that poor people and ethnic minorities have higher cancer rates in some instances. The Institute of Medicine (IOM), which is part of the National Academy of Sciences, chartered the Committee on Cancer Research Among Minorities and the Medically Underserved. Representatives from the Robert Lurie Cancer Center, Fox Chase Cancer Center, Memorial Sloan-Kettering Cancer Center, and the Stanley S. Scott Cancer Center sat on the committee, which was chaired by M. Alfred Haynes, the former president and dean of the Drew Postgraduate Medical School.

Researchers have identified a mechanism that may explain where colorectal tumors arise and at what age the tumors develop in people with hereditary nonpolyposis colorectal cancer (HNPCC). The results of the study, conducted at Ohio State’s Comprehensive Cancer Center, help clarify why some people with the same HNPCC-related genetic mutation develop colorectal tumors at 30 years of age while others develop tumors at age 60. They also help explain why tumors in some patients develop in the distal area of the large intestine rather than in regions closer to the large intestine’s junction with the small intestine, which is more typical.

Actress Jane Seymour, a strong advocate of alternative cancer therapies, was the headlining witness at hearings of the Government Reform Committee held on February 24. Rep. Dan Burton (R-Ind.), chairman of the committee, held the hearings to find out whether federal agencies-be they health care providers, such as Medicare, or research-based, such as the NCI-are aggressive enough in promoting alternative therapies. Those like Burton, who feel that federal agencies have to be more aggressive, support the “Access to Medical Treatment Act,” a bill promoted in the last two Congresses, and again in this one, by Rep. Peter DeFazio (D-OR). DeFazio’s bill had a hearing in 1998 in Burton’s committee, which has no legislative jurisdiction.

Rituximab (Rituxan), a chimeric monoclonal antibody (MoAb), binds with high affinity to the CD20 antigen found on malignant and normal B-cells, but not on other normal tissues. CD20 is an attractive target because of the accessibility and sensitivity of malignant B-cells to lysis via immune effector mechanisms. This MoAb mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. Also, it has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis in vitro.

Rituximab (Rituxan) was recently approved for use in relapsed and previously treated low-grade non-Hodgkin’s lymphoma (NHL); however, little data exist regarding the safety of this agent in patients with hematologic malignancies who have a high number of tumor cells in the blood. We describe our preliminary experience with two such patients in whom we noted a rapid reduction of blood tumor cells, which was associated with severe pulmonary infusion-related toxicity and thrombocytopenia. Two additional patients were collected from physician-submitted reports of adverse events related to rituximab treatment.

With the aim to overcome the limitations of ex vivo bone marrow purging, we have assessed the ability of the anti-CD20 monoclonal antibody rituximab (Rituxan), given in combination with chemotherapy, to eradicate polymerase chain reaction (PCR)–detectable disease, and to enable the harvesting of large amounts of uncontaminated peripheral blood progenitor cells in patients with low-grade lymphoma (in vivo purging). From April 1997 to July 1998, 20 consecutive patients entered the study. Eligibility included age £ 60 years, a diagnosis of untreated mantle cell lymphoma or of refractory/early relapsed follicular lymphoma, CD20 expression by tumor cells, histologic bone marrow infiltration, and availability of a molecular marker for minimal residual disease detection.