Growth Factors ReduceToxicity, Allow Greater DoseIntensity in Elderly PatientsWith Cancer

BETHESDA, MD-Older cancer patients should receive adequate prophylaxis with growth factors to ensure that they can receive full-dose chemotherapy without dose reductions, according to Ralph V. Boccia, MD. If doses are reduced or delayed because of cytopenia, the treatment might be less successful; in fact, there are very few cases in which doses for the fit elderly should be reduced: "You won't end up with the outcome, and you will still end up with the toxicity," said Dr. Boccia, director of research at the Center for Cancer and Blood Disorders, Bethesda, Maryland. There is ample evidence, he said, to show that age is not a contraindication to standard-dose chemotherapy for lung, breast, colorectal, and prostate cancer, along with non-Hodgkin's lymphoma. Cancer patients more than 65 years of age are less tolerant of chemotherapy, and they have a higher risk of adverse effects such as neutropenia and anemia. However, fit older patients who receive adequate prophylaxis now appear to be able to tolerate the bone marrow suppression caused by their treatment. Benefits of Growth Factors "There are effective ways to cope with treatment-related toxic effects," said Dr. Boccia. For example, multiple trials have shown that hematopoietic growth factors reduce the incidence of neutropenia, and more importantly neutropenic infections, vs no administration of growth factors. In proposed guidelines, expertsrecommended that patients aged 70 years or older receive hematopoietic growth factors such as filgrastim(Drug information on filgrastim) in any combination chemotherapy regimen that has dose intensity equivalent to CHOP (cyclophosphamide [Cytoxan, Neosar]/doxorubicin HCl/ vincristine [Oncovin]/prednisone) or AC (doxorubicin/cyclophosphamide). In addition, the experts say hemoglobin (Hb) should be maintained at 12 g/dL or above with erythropoietic agents (Oncology 14:221- 227, 2000). For elderly patients, erythropoietic agents can help ameliorate fatigue, complications of anemia and chemotherapy toxicity. Studies (J Clin Oncol 19:2865-2874, 2001) have shown that correcting anemia this way may improve survival in cancer patients. Erythropoietic agents also have been shown to improve quality of life in multiple studies, including a study by Glaspy et al (The Oncologist 7:126- 135, 2002), in which investigators looked at Functional Assessment of Cancer Therapy-Anemia (FACT-An) scores relative to Hb improvement in more than 4,000 community-treated cancer patients receiving epoetin alfa(Drug information on epoetin alfa) (Procrit). Glaspy et al found that even small increases in Hb yielded improvements in quality of life. "This can even occur in patients with progressive dis-ease, if you correct anemia, which is pretty striking," Dr. Boccia said. CHOP-14 Plus G-CSF Superior to CHOP-21 Elderly patients may also benefit from dose intensification enabled by use of growth factors. This was shown in a trial by the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) that suggested that the 14-day CHOP regimen could become the new standard regimen for NHL patients more than 60 years of age. In the DSHNHL trial, presented at the 2001 meeting of the American Society of Hematology (abstract 3027), investigators randomized more than 807 elderly patients (age range, 61 to 75 years) with aggressive NHL to 6 cycles of the typical CHOP-every-21- days schedule (CHOP-21), or one of three comparator arms: CHOP every 21 days plus etoposide(Drug information on etoposide) (CHOEP-21); dose-intensive CHOP every 14 days (CHOP-14) plus granulocyte colonystimulating factor (G-CSF [Neupogen]) support; or dose-intensive CHOP plus etoposide every 14 days (CHOEP-14) plus G-CSF support. Relative dose intensities were 95% for CHOEP-21 and 93% for CHOP- 14 plus. "Clearly, they were able to maintain dose intensity [by] giving cytokine therapy [with] these two regimens," Dr. Boccia said. For standard CHOP-21, the complete response rate was 63.2%, compared with 77% for dose-intense CHOP-14 with G-CSF support (P = .009). At a median of 40 months' observation time, overall survival was 49% for CHOP-21 and 64.3% for CHOP-14 (P = .04). "What was impressive was that the response rate looked quite good," said Dr. Boccia. "If you intensify using cytokine support, the response rate is higher and overall survival appears to be up."