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In Very Old Patients, Minimal Toxicity, Stable Disease May Trump Response or Survival Benefit

In Very Old Patients, Minimal Toxicity, Stable Disease May Trump Response or Survival Benefit

BOCA RATON, Florida- Cancer treatment "success" in the very elderly may depend not as much on improving survival or achieving response as on stabilizing disease or delaying progression while minimizing toxicity, according to Alan J. Koletsky, MD. Clinical trials traditionally focus on end points such as response rate, median survival, or overall survival. But for older people with a life expectancy of less than 10 years, these outcomes may not be relevant, said Dr. Koletsky, an oncologist with the Center for Hematology- Oncology, in Boca Raton, Florida. Relevant Outcomes "If you offered a patient the choice of having stable disease for a period of at least 6 months with a reasonably good quality of life or a short-lived response achieved without insignificant toxicity, he or she might prefer the former, which in a traditional phase II study might not be considered a response," Dr. Koletsky said. Notably, a number of clinical development efforts have aimed at enhancing drug tolerance without sacrificing the efficacy of therapy: Enhancing Drug Tolerance, Preserving Efficacy

  • Low-dose weekly schedule- Docetaxel (Taxotere) is one drug that has been evaluated on a low-dose weekly schedule, which has a more favorable safety profile compared with the conventional every-3-weeks schedule, according to Dr. Koletsky. In patientswith prostate cancer, prostate-specific antigen (PSA) levels and objective response rates are similar to those seen with the conventional schedule (Ann Oncol 12:1273-1279, 2001; Proc ASCO 18:3335A, 1999). Moreover, docetaxel may have an additional mechanism of action, angiogenesis inhibition, when given weekly (Int J Cancer 104(1):121-129, 2003.
  • Pegylated liposomal derivatives- These are active and well tolerated versions of other drugs such as cisplatin, anthracyclines, or interferon alfa. Liposomal anthracyclines have been used in breast cancer, ovarian cancer, and myeloma. The spectrumof toxicity is different from that seen with traditional anthracycline therapy. "Hand-foot syndrome is more commonly seen," Dr. Koletsky said, "but a number of toxicities common in the elderly, such as mucositis, hair loss, and cardiotoxicity, are really limited."
  • Capecitabine (Xeloda)-This agent, the tumor-activated fluorouracil (5-FU) has been favored in the elderly, according to Dr. Koletsky. It is convenient and relatively well tolerated, and its pharmacology is not significantly influenced by age or liver function. "This is one of the few drugsfor which the package insert indicates a higher dose than we may eventually use," he said.
  • Epirubicin in breast cancer- Researchers have compared low-dose weekly epirubicin (Ellence) with gemcitabine (Gemzar) as first-line treatment in elderly women (more than 70 years of age) with metastatic breast cancer. Time to progression favored epirubicin (6.1 vs 3.4 months), as did response rate (40% vs 16%). There was also somewhat less grade 3 to 4 neutropenia in the epirubicin arm (18% vs 26%)(Eur J Cancer 37[suppl 6, S146]:110, 2001).
  • Oral targeted therapies-The agent gefitinib (Iressa) may reduce symptoms related to disease, data show. In a phase II trial including patients with non-small-cell lung cancer who received gefitinib following failure of one or two chemotherapy regimens, about 40% had improvement in disease-related symptoms (ASCO 2002, abstract 1167).
  • A majority of partial responders (78%) had symptom improvement, as did more than half of patients with stable disease. Progression-free survival time was 4.2 months in patients who had improvement in disease-related symptoms, vs 2.0 months for those who did not. "This is an example of taking a group of patients who would normally have a poor quality of life, and affording them the possibility of stable disease and a reasonably good quality of life," Dr. Koletsky said.
     
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