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

December 1, 2003

This special supplement to Oncology News International presents 17 reports fromthe first annual Geriatric Oncology Consortium (GOC) multidisciplinary conference,‘‘Advancing Cancer Care in the Elderly.’’ Reports focus on issues in geriatric oncology,in particular team-based patient assessment and care delivery,adherence to medication, accrual to clinical trials, appropriate dosingthrough supportive therapy, radiation therapy, cognition problems, pain management,reassessment of outcomes, and caregiving issues.

BOCA RATON, Florida-Cancer treatment "success" in the veryelderly may depend not as much onimproving survival or achieving responseas on stabilizing disease or delayingprogression while minimizingtoxicity, according to Alan J. Koletsky,MD.Clinical trials traditionally focus onend points such as response rate, mediansurvival, or overall survival. Butfor older people with a life expectancyof less than 10 years, these outcomesmay 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 choiceof having stable disease for a period ofat least 6 months with a reasonablygood quality of life or a short-livedresponse achieved without insignificanttoxicity, he or she might preferthe former, which in a traditional phaseII study might not be considered aresponse," Dr. Koletsky said.Notably, a number of clinical developmentefforts have aimed at enhancingdrug tolerance without sacrificingthe efficacy of therapy:Enhancing Drug Tolerance,Preserving Efficacy

  • Low-dose weekly schedule-Docetaxel (Taxotere) is one drug thathas been evaluated on a low-dose weeklyschedule, which has a more favorablesafety profile compared with theconventional every-3-weeks schedule,according to Dr. Koletsky. In patientswith prostate cancer, prostate-specificantigen (PSA) levels and objectiveresponse rates are similar to those seenwith the conventional schedule (AnnOncol 12:1273-1279, 2001; Proc ASCO18:3335A, 1999). Moreover, docetaxelmay have an additional mechanismof action, angiogenesis inhibition,when given weekly (Int J Cancer104(1):121-129, 2003.
  • Pegylated liposomal derivatives-These are active and well toleratedversions of other drugs such ascisplatin, anthracyclines, or interferonalfa. Liposomal anthracyclines havebeen used in breast cancer, ovariancancer, and myeloma. The spectrumof toxicity is different from that seenwith traditional anthracycline therapy."Hand-foot syndrome is morecommonly seen," Dr. Koletsky said,"but a number of toxicities commonin the elderly, such as mucositis, hairloss, and cardiotoxicity, are really limited."
  • Capecitabine (Xeloda)-Thisagent, the tumor-activated fluorouracil(5-FU) has been favored inthe elderly, according to Dr. Koletsky.It is convenient and relatively well tolerated,and its pharmacology is notsignificantly influenced by age or liverfunction. "This is one of the few drugsfor which the package insert indicatesa higher dose than we may eventuallyuse," he said.
  • Epirubicin in breast cancer-Researchers have compared low-doseweekly epirubicin (Ellence) with gemcitabine(Gemzar) as first-line treatmentin elderly women (more than 70years of age) with metastatic breastcancer. Time to progression favoredepirubicin (6.1 vs 3.4 months), as didresponse rate (40% vs 16%). Therewas also somewhat less grade 3 to 4neutropenia in the epirubicin arm(18% vs 26%)(Eur J Cancer 37[suppl6, S146]:110, 2001).
  • Oral targeted therapies-Theagent gefitinib (Iressa) may reducesymptoms related to disease, datashow. In a phase II trial including patientswith non-small-cell lung cancerwho received gefitinib following failureof one or two chemotherapy regimens,about 40% had improvementin disease-related symptoms (ASCO2002, abstract 1167).

A majority of partial responders(78%) had symptom improvement, asdid more than half of patients withstable disease. Progression-free survivaltime was 4.2 months in patientswho had improvement in disease-relatedsymptoms, vs 2.0 months forthose who did not."This is an example of taking agroup of patients who would normallyhave a poor quality of life, and affordingthem the possibility of stabledisease and a reasonably good qualityof life," Dr. Koletsky said.