ONCOLOGY Vol 13 No 3

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).

Patients with advanced Hodgkin’s disease-Ann Arbor stage IIB to IV-were randomized to treatment with either four

We have previously shown that disease status at the time of autologous bone marrow transplant (BMT) and relapse in a prior radiation field are the most important predictors of outcome for patients with relapsed or primary refractory Hodgkin’s disease (J Clin Oncol 11:704,1993). We have extended this analysis to include 194 patients treated at our center, with a median follow-up of 5 years (range, 1 month to 10 years). All patients were treated with salvage chemotherapy (usually DHAP [dexamethasone, ara-C, and Platinol] or mini-BEAM [BCNU, etoposide, ara-C, and melphalan]) to maximum response, and received the same high-dose chemotherapy regimen, consisting of etoposide (60 mg/kg) and melphalan (160 mg/m²).

African-Americans are leading the fight against breast cancer in communities across the country. The Witness Project, the East-West Breast Express, and the Navigator Program are just a few examples of innovative programs funded by the Susan G. Komen Breast Cancer Foundation and their local affiliates that are improving the future for many African-American women.

Aphase III clinical trial conducted by researchers at Lehigh Valley Hospital, Allentown, Pennsylvania, found that the OncoVAX colon cancer vaccine reduced the 5-year recurrence rate of patients with stage II colon cancer patients by 61% and improved their cancer-free survival rate by 50%. The study, published in a recent issue of the Lancet, compared patients who underwent surgery alone to patients who had surgery plus the vaccine.

The success of purine nucleoside analogs in the treatment and management of indolent leukemias has generated interest in

A cooperative national clinical trial has produced the first major treatment advance in years for small-cell lung cancer. The study, which was published in the February 1999 issue of the New England Journal of Medicine, used two treatments of radiation daily, combined with chemotherapy, compared to the usual practice of delivering one radiation dose per day. Specifically, the protocol covered small-cell lung cancer limited to one-half of the chest area.

Clinical trials with yttrium-90 and iodine-131 radioimmunotherapy have demonstrated efficacy in the treatment of non-

Transformation from indolent B-cell non-Hodgkin's lymphoma (NHL) to a more aggressive histology occurs frequently in the natural history of these diseases, and is generally associated with a poor prognosis. Histologic conversion occurs in 25%-80% of patients with follicular NHL, but is less frequently seen in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), reported in 3%-10% of patients. Between December 1982 and August 1997, 27 patients (14 male, 13 female) with a history of indolent B-cell NHL/CLL that had transformed to diffuse large B-cell lymphoma (DLCL) underwent autologous bone marrow transplantation (BMT). All patients were previously treated for indolent NHL/CLL with a median of threeprior therapies, and were similar with respect to whether transformation occurred early (< 18 months from diagnosis) or late.

Unlabeled monoclonal antibodies (MoAbs) are attractive for the treatment of non-Hodgkin’s lymphoma (NHL) as they may: (1) mediate cytotoxicity with complement (complement-dependent cytotoxicity [CDC]) or effector cells (antibody-dependent cellular cytotoxicity [ADCC]); (2) effect apoptosis; (3) be less toxic, less immunogenic, and more effective than toxin- or drug-conjugated MoAbs; (4) not require the complex procedures needed for radiolabeled MoAb therapy (RIT); and (5) not produce the myelosuppression typical of high-dose RIT.

Rituximab (Rituxan) is the first monoclonal antibody (MoAb) approved for the treatment of non-Hodgkin’s lymphoma (NHL). This anti-CD20 MoAb is effective in inducing apoptosis, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC). In single-agent studies in relapsed or refractory low-grade or follicular NHL (International Working Formula [IWF] types A-D), an overall response rate (ORR) of 48% has been reported.

Age is a risk factor and a prognostic parameter in elderly high-grade non-Hodgkin’s lymphoma (NHL) patients. Several

Drs. Peeters and Haller provide a thorough review of the recent historical development, current state of knowledge, and future of adjuvant therapy for early-stage colon and rectal cancers. They provide reasonable recommendations for the

This review of the use of brachytherapy (also known as interstitial or intracavitary radiation therapy) in children with soft-tissue sarcomas is well-written and timely. The authors have done an excellent job of summarizing the characteristics of the

The article by Drs. Peeters and Haller provides the details of 20 years of investigation into the adjuvant therapy of colorectal cancer. The authors describe pivotal trials through which an international cast of investigators have identified adjuvant

Dr. Nag and colleagues provide an overview of brachytherapy, describe its application in pediatric oncology, and review the clinical experience in childhood solid tumors. The limited number of publications includes Dr. Nag’s own important, innovative clinical research using remote afterloading high-dose-rate (HDR) brachytherapy with twice-daily fractions in children with sarcoma.[1]

The CHOP (cyclophosphamide, doxorubicin, Oncovin, and prednisone) regimen has been the standard approach to patients with advanced-stage intermediate-grade non-Hodgkin’s lymphoma (NHL) for more than 20 years.A randomized comparison between CHOP, m-BACOD (methotrexate, bleomycin, Adriamycin, cyclophosphamide, Oncovin, and dexamethasone).

The currently available nucleoside analogs, such as fludarabine, have revolutionized the approach to the treatment of indolent lymphoid malignancies. Fludarabine is the most effective agent for the treatment of chronic lymphocytic leukemia (CLL) and also exhibits major activity in low-grade NHL. Despite the impressive rates of complete remissions, patients with these malignancies remain incurable, and new agents are needed.

The role of interferon-alfa (Intron A, Roferon) in the management of patients with low-grade NHL remains controversial. More than 10 randomized trials have been reported.

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.

High-dose chemotherapy with autologous stem-cell support has clearly demonstrated efficacy in patients with relapsed or refractory Hodgkin’s disease (Horning et al: Blood 89:801-813, 1997) and is probably superior to salvage chemotherapy in this setting (Yuen et al: Blood 89:814-822, 1997). Disease burden and chemosensitivity have been shown to be predictive of long-term outcome following the transplant. However, a clear advantage may be difficult to demonstrate because of late complications, including secondary malignancies, particularly acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) (Roberts et al, abstract #2984).

The relative clinical efficacy of autologous or allogeneic bone marrow transplantation (BMT) remains a controversial issue. In most series, outcomes with the two types of transplants have been comparable; relapse is more common with autologous BMT due to contamination of stem cells, whereas allogeneic BMT is associated with greater treatment-related mortality.

The use of all-trans-retinoic acid (ATRA [Vesanoid]) has revolutionized the treatment of patients with acute promyelocytic leukemia (APL)(Tallman et al: N Engl J Med 337:1021-1028, 1997). However, a significant proportion of patients still relapse and die from their disease. Studies from China have indicated that arsenic trioxide is effective even in patients who did not respond to ATRA, and subsequent research has suggested that it works by a different mechanism of action (Shen et al: Blood 89:3354-3360, 1997).

As more new therapeutic agents enter clinical trials, it becomes increasingly more important to have standardized response criteria. Uniform guidelines facilitate acquisition of comparable data, interpretation of data, comparisons of the results among various clinical trials, and identification of new agents with promising activity.

The role of combined-modality therapy for Hodgkin’s disease was the subject of several abstracts presented at the ASH meeting. Radiation therapy has traditionally been the standard approach for patients with early-stage disease. However, several recent studies have suggested an important role for chemotherapy, either alone or in combination with radiation.

Rituximab is a chimeric human-mouse anti-CD20 monoclonal antibody that has been studied most widely in patients with follicular non-Hodgkin’s lymphomas (NHLs). This antibody has induced responses in about half of these cases, including a 6% complete remission rate, with responses lasting a median of 11.6 months (McLaughlin et al: J Clin Oncol 16:2825-2833, 1998). Rituximab has only entered widespread clinical use over the past year. As a result, data are just beginning to emerge on the long-term results with this agent.

Gerhartz and coworkers (abstract #1293) and the German Hodgkin’s Group (Diehl et al, abstract #2002) presented their results with interoup (Diehl et al, abstract #2002) presented their results with intensified regimens. The former investigators used a time-intensified COPP (cyclophosphamide, Oncovin, procarbazine, and prednisone)/ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine, Prokine]) support. Complete remission rates were 62% with COPP/ABVD, as compared with 79% for the intensified regimen. This was taken as evidence of benefit from the higher-dose program. However, these findings are consistent with results that have been reportedfor ABVD and other anthracycline-containing regimens (Canellos et al:N Engl J Med 327:1478-84, 1992; Duggan et al: Proc Am Soc Clin Oncol 16:12a [abstract 43], 1997).

Although thousands of patients have been treated with rituximab to date, researchers are just beginning to understand the basis on which this agent works. Rituximab is believed to induce tumor regression by several mechanisms of action, including antibody-dependent cellular cytotoxicity (ADCC), complement-mediated cytotoxicity (CDC), and induction of apoptosis. The mechanism by which apoptosis occurs also has not been clearly elucidated.

In general, rituximab has an acceptable toxicity profile. However, as the drug has been used more widely, new side effects have been identified that warranted a modification of the package insert. Approximately 70 serious infusion-related events have been reported, with 8 fatalities out of an estimated14,000 patients treated. Death was associated with bronchospasm, hypotension, and severe respiratory distress, with no clear predisposing factors.

Allogeneic BMT has generally been limited to patients younger than age 50 to 55 years, and to those with good performance status and renal function. Several approaches are being evaluated to allow these poorer-risk patients to safely undergo transplantation. The successful use of submyeloablative (“mini”) transplants has previously been reported by groups from Israel (Slavin et al: Blood 91:756-73, 1998) and M. D. Anderson (Khouri et al: J Clin Oncol 16:2817-2824, 1998). A moderately myelosuppressive agent, such as cyclophosphamide (Cytoxan, Neosar), and an immunosuppressive drug, such as fludarabine (Fludara), are used as the preparative regimen. Following BMT, allogeneic donor leukocytes may be used to eliminate residual disease or mixed chimerism. Further study of this interesting approach is ongoing.