Use of Chemotherapy Supported for Elderly Despite Side Effects

BOSTON—The elderly may suffer more from the side effects of chemotherapy, but toxicity should not necessarily prevent them from receiving life-saving or palliative treatment, according to two speakers at the 14th international meeting of the Multinational Association for Supportive Care in Cancer (MASCC) and International Association for Oral Oncology.

Matti S. Aapro, MD, of the Institut Multidisciplinaire d’Oncologie, Genolier, Switzerland, urged greater use of supportive care—including prophylactic use of agents such as filgrastim (Neupogen); pegfilgrastim (Neulasta); epoetin alfa (Epogen, Procrit); and darbepoetin alfa (Aranesp)—to ensure that elderly patients can complete chemotherapy cycles on schedule. "Existing means of supportive care should allow adequate chemotherapy use in almost every person who may need this approach for cure or efficacious palliation of cancer," he said.

Carsten Bokemeyer, MD, of Tuebin-gen University Hospital, Germany, recommended sequential single-agent therapies for most elderly patients until clinical trials prove combination therapies to be superior for this population. Each combination therapy has to be considered separately, he said, cautioning that in many cases they have not been proven more beneficial than single-agent therapies for patients, regardless of age.

Both Drs. Aapro and Bokemeyer complained of a lack of data on toxicity in the elderly. "Most new trials have excluded elderly patients," Dr. Bokemeyer said. Oncologists considering combination treatments often find "no clear correlation of dose intensity and toxicity and age," he said.

Dr. Aapro reported that a literature review found patients over the age of 70 had a significantly higher incidence of grade 3-4 neutropenia, neutropenic infections, anemia, and thrombocytopenia when given CHOP-like regimens. In nine studies of elderly patients given chemotherapy for non-Hodgkin’s lymphoma, the risk of life-threatening neutropenia was greater than 40%, he said, while the risk of associated infections ranged from 21% to 47%.

Similarly, he said, when given CMF (cyclophosphamide, methotrexate, fluorouracil), breast cancer patients above the age of 65 have more than twice as much grade 3 hematologic toxicity as younger patients: 9.2% vs 4.5%.

He cited myelosuppression as the most common chemotherapy-induced toxicity and said depleted hematologic stem cell reserves and/or chronic disease is the most common complicating factor in elderly patients.

Preventing anemia is especially important because "anemia impairs the function of virtually every organ and tissue," he said, urging prophylactic use of erythropoietin. "The American Society of Clinical Oncology recommends prophylactic hematopoietic growth factors," Dr. Aapro said. "In many countries, this is not done."

He concluded with a call for MASCC to develop joint guidelines with other leading cancer organizations on supportive care for elderly patients. The European Organization for Research and Treatment of Cancer (EORTC) is preparing guidelines for the management of myelo-suppression in elderly cancer patients, according to Dr. Aapro, who also presented guidelines that have been proposed by the National Comprehensive Cancer Network (NCCN).

The Societé Internationale d’Oncolo-gie Geriatrique (SIOG) is working on geriatric assessment guidelines, and MASCC committees are doing similar work with respect to mucositis, antibiotics, and antiemetics, he said.

Combination Therapies

Dr. Bokemeyer presented the emergence of combination therapies as particularly vexing for oncologists treating elderly patients. Many chemotherapies are as effective in older patients as in younger patients, he said, but fear of toxicity in elderly patients has resulted in a preference for single-agent regimens. Adding to the difficulty, he said, is that strict comparison of single-agent and combination therapies has not been done in many situations, so "the answer to which is better cannot be given for the elderly patient."

One factor to consider, Dr. Bokemeyer suggested, is whether the combination therapy results in a survival gain that outweighs the increased costs and toxicity. "Although combination regimens may achieve higher response rates, the impact on overall survival, even in younger patients, has only been demonstrated in a few specific situations," he said.

Sequential Single-Agent Therapy

Combination chemotherapy is feasible in elderly patients who do not have comorbidities and are generally in good health, he said. For the majority of patients, however, he suggested that sequential single-agent chemotherapy remains the treatment of choice, with the caveat that "it remains open whether to start slower." For the frail elderly, he added, most cytotoxic therapy is to be avoided.

In all cases, Dr. Bokemeyer said, the decision between curative treatment and palliative care needs to be discussed with the patient. "This basic question has not been answered independent of age," he said.