Alternatives to Standard Chemotherapy Prolong Survival in Lymphoma, Leukemia Patients

ORLANDO, Fla., Dec. 9 /PRNewswire/ -- Chemotherapy, the most common type of treatment for cancer patients, can cause troublesome side effects, such as nausea and vomiting, hair loss, fatigue, and life-threatening toxicities. An important area of progress has been the development of minimally toxic non- chemotherapy agents that add to the effectiveness of chemotherapy. Three studies being presented today at the 48th Annual Meeting of the American Society of Hematology (ASH(TM)) highlight the benefits of alternative treatments to standard chemotherapy.

"These treatment studies demonstrate the promise of biologic agents that can be used as substitutes or as additions to chemotherapy in the treatment of many cancers," said Charles A. Linker, MD, University of California, San Francisco. "These new treatments are fulfilling the promise of research based on improved understanding of the cancer cell. We are able to offer treatments that both improve outcomes and preserve quality of life."

Novel Treatment of Burkitt Lymphoma with Dose-Adjusted EPOCH-Rituximab: Preliminary Results Showing Excellent Outcome [Abstract #2736]

Burkitt lymphoma (BL) is a rare and highly aggressive cancer that has several clinical variants. The "endemic" form occurs in Africa where it represents the most common childhood cancer. The "sporadic" form is most common in western countries, and primarily occurs in children and young adults, but can also affect older individuals and HIV-infected patients.

Symptoms of the disease vary widely. Patients with endemic BL often experience facial bone or jaw swelling, loose teeth, and swollen lymph nodes. Sporadic BL patients most often develop abdominal tumors or symptoms of bowel obstruction, and HIV-associated BL usually presents with lymph node and bone marrow disease. Because of the very aggressive nature and rapid growth rate of BL, effective treatment is urgently needed. Current treatments involve intensive multi-agent chemotherapy and are highly effective but very toxic, particularly in both older and HIV-infected patients.

Previous research at the National Cancer Institute (NCI) has shown that dose-adjusted (DA) EPOCH and rituximab (DA-EPOCH-R -- a combination chemotherapy regimen) is well tolerated and effective in another aggressive lymphoma called diffuse large B-cell lymphoma. Based on the hypothesis that DA-EPOCH-R would be effective in BL because of its rapid growth rate, researchers at NCI initiated a study.

A total of 17 eligible patients with untreated BL were enrolled in the trial that included both HIV-negative and HIV-positive patients. More than half (53 percent) of participants had advanced disease (stage III/IV, 9 patients), and 65 percent had disease that spread to other body organs (11 patients). HIV-negative patients (n=13) received six cycles of DA-EPOCH-R, and HIV-positive patients (n=4) received an average of only three cycles to reduce chemotherapy damage to the immune system.

In this study, DA-EPOCH-R was extremely successful. All patients achieved complete remission and tolerated the treatment well. One patient also received additional radiotherapy to a site of remaining disease. After an average follow-up of 28 months, all patients were alive and in remission. Compared to standard treatments for BL, patients receiving the DA-EPOCH-R regimen experienced low toxicity, with only 10 percent of treatment cycles requiring hospitalization for low blood counts and fever.

"These preliminary results suggest that DA-EPOCH-R is highly effective in treating Burkitt lymphoma and at the same time is very well tolerated in all age groups," said Kieron Dunleavy, MD, National Cancer Institute. "DA-EPOCH-R represents a fundamental departure from standard chemotherapy strategies and may significantly advance the therapeutic index of Burkitt lymphoma treatment."

Front-Line Combined Immuno-Chemotherapy (R-CHOP) Significantly Improves the Time to Treatment Failure and Overall Survival in Elderly Patients with Advanced Stage Follicular Lymphoma-Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG) [Abstract #482]

Follicular lymphoma (FL) is a common type of non-Hodgkin lymphoma characterized by follicular growth and a low-grade, slow growth pattern in the lymph nodes. FL occurs in elderly patients, who often are well over 60 years old, and despite improvement of therapeutic concepts, FL remains incurable in the advanced stages of disease. Therefore, the key challenge for the future is to develop treatment strategies that can improve treatment outcome without adding major side effects.

To test the value of combination therapies with chemo and new targeted therapies, rituximab was added to the common combination chemotherapy "CHOP" (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the German Low Grade Lymphoma Study Group (GLSG) conducted by researchers at the Klinikum Grosshadern, Munich, Germany. In an analysis focusing on treatment effect on elderly patients in the study cohort, investigators collected data on 221 patients more than 60 years of age during a multicenter, phase III, randomized study of R-CHOP (CHOP with one infusion of rituximab (375 mg/m2) on the day before the start of chemotherapy; 109 patients) versus CHOP alone (112 patients) in advanced stage, untreated FL. The two groups were similar in patient characteristics, in particular their risk profile. The CHOP combination chemotherapy, with or without rituximab, was given for six to eight cycles. Study results showed that elderly patients responded well to the combination therapy and, importantly, tolerated the R-CHOP chemotherapy regimen without any additional toxicities, compared to CHOP chemotherapy alone. Patients in both groups experienced similar side effects of treatment, predominantly myelosuppression (reduced production of blood cells).

Patients who received R-CHOP had a higher overall response rate and longer time to treatment failure (TTF) than patients who received CHOP alone (5.0 years vs. 2.1 years). The estimated four-year progression-free survival was 62.2 percent for R-CHOP patients, compared to just 27.9 for CHOP patients. Most importantly, the use of R-CHOP prolonged the overall patient survival compared to CHOP alone, at 90 percent versus 81 percent, respectively. In further analyses, individual factors such as elevated serum levels, low hemoglobin levels, number of nodal areas (>4), and application of CHOP alone were independently associated with a shorter TTF.

"The addition of rituximab to CHOP in treating advanced stage follicular lymphoma significantly improves the outcome of patients with previously untreated follicular lymphoma, not only in young patients, but also in patients of advanced age," said Christian Buske, MD, Klinikum Grosshadern, Munich, Germany. "The efficacy and low side effects of R-CHOP suggest that the addition of rituximab to standard therapy may offer doctors and patients a better option when choosing treatment for the disease."

Long-Term Follow-Up Confirms the Benefit of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL) [Abstract #565]

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) representing approximately 10-15 percent of all adult AML cases. The prognosis of APL has been poor, mainly due to characteristic hemorrhagic (bleeding) complications, which can be aggravated by chemotherapy and lead to early death. Since 1986, the innovative application of all-trans retinoic acid (ATRA) in APL treatment in China has dramatically improved the clinical outcome of patients, and the complete rate of remission has increased to 90-95 percent. After further consolidation and maintenance therapy using ATRA and chemotherapy, the five-year overall survival reached 60-70 percent. Subsequently, arsenic trioxide (As2O3) has proven to be another effective agent for both relapsed and newly diagnosed APL cases, and has become a current standard therapy for relapsed patients with previous treatment of ATRA and/or chemotherapy.

Even with these encouraging statistics, a sizable proportion of patients have relapsed and become resistant to treatment. To further improve the clinical outcome of APL patients, optimization of treatment protocol is warranted. This molecular study demonstrated that both ATRA and As2O3 directly targeted a specific protein (the leukemic PML-RARalpha fusion protein) through different pathways, and a significant synergy in eradicating leukemia in mice was observed.

These results prompted a team of researchers from the Shanghai Institute of Hematology to test a strategy combining ATRA and As2O3 in front-line treatment for newly diagnosed APL. Once complete response (CR) was achieved, the patients were given three courses of consolidation chemotherapy and then five cycles of sequential treatment of ATRA, As2O3, and methotrexate (6- MP/MTX).

To further confirm the long-term benefit, the team compared the study group to patients receiving front-line therapy of ATRA and chemotherapy. Through the last follow-up in April 2006, two of the 56 patients underwent extramedullary relapse and one also relapsed in marrow. Both patients obtained and maintained a second CR with rescue treatment consisting of ATRA/As2O3 and chemotherapy. A third patient died suddenly with suspected CNS leukemia. The other 53 patients were alive and remained in hematologic remission. With a median follow-up of 48 months (25-60 months), the four-year overall survival and event-free survival were estimated at 98.1 percent and 94.2 percent, respectively. For the historical group with a median follow-up of 56 months (12-79 months), the four-year overall survival and event-free survival were estimated at 83.4 percent and 45.6 percent.

"These data clearly demonstrated a benefit of front-line combination of ATRA and As2O3 in terms of overall or event-free survival," said Sai-Juan Chen, MD, Deputy Director, Shanghai Institute of Hematology and senior author of the study. "It is also showing that the protocol is simple and convenient enough to be carried out even in an outpatient department, which significantly improves the quality of life. With prolonged follow-up, we hope that we can define a curative treatment for this disease."

The American Society of Hematology (http://www.hematology.org/) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.