MINNEAPOLIS-The Cancer and Leukemia Group B (CALGB) investigators have undertaken a number of "provocative" studies, not only of cancer therapy in the elderly but also of pharmacokinetics and barriers to clinical trial participation for older cancer patients, according to Vicki Morrison, MD. The studies are under the direction of the CALGB Cancer in the Elderly Committee, an outgrowth of the Elderly Working Group formed about a decade ago to address issues specific to older patients, said Dr. Morrison, associate professor of medicine at the University of Minnesota, Minneapolis. Therapy Trials in the Elderly One important Committee investigation underway is CALGB 9793/ ECOG-SWOG 4494. This phase III intergroup trial compares CHOP (cyclophosphamide [Cytoxan, Neosar]/ doxorubicin(Drug information on doxorubicin) HCl/vincristine [Oncovin]/ prednisone(Drug information on prednisone)) chemotherapy vs CHOP plus rituximab(Drug information on rituximab) (Rituxan) in stage I to IV non-Hodgkin's lymphoma patients 60 years of age and older. The study includes 632 patients with previously untreated diffuse large cell B-cell lymphoma and performance status 0 to 3. Following an induction randomization to CHOP or CHOPrituximab, responders are further randomized to maintenance rituximab for 6 or 8 cycles (every 6 months for 2 years if the IgG level is above 500 units/ mL) or observation. Ancillary studies are planned in CALGB 9793, including one that correlates dose intensity with outcome. "There have been series reported over the years saying older people do morepoorly with this disease because they are given lower doses of chemotherapy, so that's one aspect that will be looked at," Dr. Morrison said. The CALGB Cancer in the Elderly Committee also has an ongoing study of postoperative therapy for elderly breast cancer patients. The study, CALGB 49907, compares capecitabine(Drug information on capecitabine) (Xeloda) with CMF (cyclophosphamide [Cytoxan, Neosar], methotrexate, and fluorouracil) or AC (doxorubicin and cyclophosphamide(Drug information on cyclophosphamide)) chemotherapy in women with operable breast adenocarcinoma. About 110 patients have been enrolled in the trial so far. At the 2003 meeting of the American Society of Clinical Oncology (ASCO), CALGB committee co-chair Hyman Muss, MD, reported a breast cancer study of the relationship between age and outcome in node-positive women who received adjuvant therapy (ASCO abstract 11). The results show that older patients had more treatment-related deaths, said Dr. Muss, professor of medicine and associate director for clinical research, Vermont Cancer Center, University of Vermont, Burlington. However, the data also suggested that older patients who undergo aggressive chemothera-py regimens derive a greater benefit vs more standard regimens, similar to what is observed in younger patients. Pharmacokinetic Trials Other of the CALGB trials are assessing the pharmacokinetics of specific chemotherapeutic agents. The ongoing CALGB 9762 trial (ASCO 2001, abstract 265) has been evaluating clearance and toxicity of paclitaxel(Drug information on paclitaxel) with advancing age. In 2001, after 3 years, there were 142 patients 55 years of age or older on study receiving paclitaxel as a single agent. Investigators found that with increasing age, there was a significant decline in total body clearance, decrease in white blood cell nadir, and increase in area under the curve (AUC). Barriers to Clinical Trial Accrual A third focus of the committee is investigating what might be done to improve accrual of elderly patients to clinical trials. In CALGB 9670, Kornblith et al reported the main barriers to accrual as reported by oncologists treating breast cancer patients at 10 of the group's sites (Cancer 95:989-996, 2002). It was the perception of these physicians that some elderly patients have significant comorbidities that may affect response to therapy. Others noted that there is a concern regarding excessive toxicity. In addition, elderly patients do not often meet eligibility criteria for trials, and even if they do meet the criteria, their compliance may be poor because of difficulty in understanding complex clinical trial protocols. A subsequently published retro-spective study (J Clin Oncol 21:2268- 2275, 2003), noting that 48% of breast cancer patients are at least 65 years old, found older breast cancer patients were significantly less likely to be offered a clinical trial. Among stage II patients, 68% of the younger patients (< 65 years old) were offered a clinical trial, vs 34% of older patients (> 65 years old) (P = .0004). When offered a trial, however, a nearly equal number of younger and older patients (about half) decided to participate. Investigators found age and stage of disease were both predictors of being offered a clinical trial, while the greatest barrier to enrolling older women was the physician's perceptions about age and toxicity tolerance. Telephone monitoring and educational interventions may reduce barriers to therapy in the elderly. A CALGB study that recently closed accrued 180 elderly breast, colorectal, and prostate cancer patients and randomized them to a telephone monitoring intervention plus educational materials, or educational materials alone. Intensive Intervention Also under study is the hypothesis that an intensive educational intervention may increase accrual of elderly cancer patients to clinical trials. In CALGB 36001, patients were randomized to a control arm or an intervention arm that included didactic symposia,a binder of materials, and email reminders. An abstract describing the study is under consideration for presentation at ASCO 2004. In the future, studies of the Cancer in the Elderly Committee may include investigations of biomarkers (eg, prostate-specific antigen) in the elderly. There are also plans to develop trials in the elderly for malignancies such as metastatic lung cancer, particularly in regard to poor-performancestatus patients. "In addition," Dr. Morrison said, "there has been some discussion of looking at chemotherapy toxicities among older patients in some of the recent CALGB studies and comparing this to older literature on this topic."