Reports

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31st Congress of the European Society of Medical Oncology

Istanbul, Turkey / September 29-October 3, 2006

According to Dr. Mario Dicato, Head of Internal Medicine, Department of Hematology-Oncology, Luxembourg Medical Centre, “More than 50% of cancers develop in patients over 65 years of age and the median age at presentation of many common cancers such as gastric cancer, pancreatic cancer and multiple myeloma is over 70 years.”

Moreover, life expectancy of affected patients is increasing. As a result, 20 years ago, one in four people in Europe would suffer cancer in the course of their lifetime; today, that figure is one in three. The challenges associated with treating cancer in elderly patients, with the emphasis on multiple myeloma, were addressed here during the scientific sessions.

Elderly Patients: A Case Apart

For a medical oncologist, elderly cancer patients may differ from younger patients in a number of ways. Dr. Silvio Monfardini, Professor of Medical Oncology, Azienda Ospedale Università, Padova, Italy, cited the presence of comorbidity, impaired functional status, mental deterioration and depression, and lack of family support. As a result, he suggested these patients require special care, supporting his opinion with the results of an Italian survey that found that “most chiefs of oncology departments agreed that special therapeutic protocols with specific guidelines were necessary for elderly cancer patients” (Monfardini et al. Crit Rev Oncol Hematol 2006; 58(1):53-9).

Unfortunately, elderly patients are often excluded from clinical trials and clinical decisions are further hindered because elderly cancer patients are a very heterogeneous group. The International Society of Geriatric Oncology (SIOG) developed an important tool, known as the Comprehensive Geriatric Assessment (CGA), which takes patient variability into account. The CGA essentially identifies three patient groups, which Dr. Monfardini described as “fit,” “vulnerable” and “frail,” and treatment varies accordingly.

For Dr. Monfardini, “Management of toxicity is an important consideration in elderly cancer patients.” Given that the life expectancy of older patients is lower, the treatment goals often differ from those of younger patients. There is perhaps more emphasis on improving quality of life than aiming for a complete cure. An important criterion for judging new treatments is therefore the toxicity profile. For the indication of multiple myeloma, bortezomib, a proteasome inhibitor, and lenalidomide, related to thalidomide, represent important advances.

Corroborative Study Findings

Dr. María Victoria Mateos, Hematology Department, University Hospital of Salamanca, Spain, presented the results from a subanalysis of the APEX (Assessment of Proteasome Inhibition on Extending Remission Results), which compared the safety and efficacy of bortezomib and dexamethasone in relapsed multiple myeloma patients. According to Dr. Mateos, “In patients over 65 years, bortezomib proved more effective than high doses of dexamethasone, and this was also reflected in a longer median time to progression.”

The next step was to investigate the addition of the proteasome inhibitor to first-line therapy because, as Dr. Mateos explained, “In elderly patients ineligible for autologous stem-cell transplant, melphalan plus prednisone [MP] is the standard treatment but the response rate is relatively poor.” This prompted a Spanish group, which included Dr. Mateos, to evaluate the addition of bortezomib to MP (MPV) in 60 untreated patients with stage I-III multiple myeloma aged 65 years or over (median age, 74 years) (Mateos et al. Blood 2006;108(7):2165-72). The overall response rate, defined as the primary efficacy end point, was 70% in the MPV arm after cycle 1. This compares with a 42% response rate after six cycles of MP therapy alone in a historical comparison.

According to the results from a subset of the study population, efficacy appeared unaffected in patients with retinoblastoma gene deletion and with heavy-chain IgH translocations, both of which are thought to be markers of poor response to MP alone. Moreover, the safety profile of MPV was acceptable and similar to previous studies in elderly patients. Toxicities could be managed satisfactorily and tended to decrease after cycle 3.

Dr. Mateos also presented studies with thalidomide, which has also been investigated as an addition to first-line MP treatment of multiple myeloma. Like bortezomib, its addition increased the number of responders, but a higher incidence of thrombotic events was observed compared to MP treatment alone.

Another new treatment related to thalidomide, lenalidomide, has also shown some promising results when added to standard MP chemotherapy in newly-diagnosed multiple myeloma. In his discussion of new treatments for multiple myeloma, Dr. Dicato cited the results from a study by Palumba et al. presented at the 2006 meeting of the American Society of Clinical Oncology. In that study, 54 patients aged 65 years or over were randomized to four different dose levels of oral lenalidomide plus MP. Overall response was 17% and partial response was 68%. The principal toxicities were grade 3/4 neutropenia (66%) and grade 3/4 thrombocytopenia (34%).

Use of thalidomide was associated with frequent thrombotic events and thromboembolism was reported in 4.8% of patients despite treatment with ASA. However, Dr. Dicato pointed out that these toxicities could generally be managed satisfactorily.

Renal Failure

Renal failure, which is common in the elderly, is often greatly exacerbated by multiple myeloma and the cancer treatment itself. Patients with renal failure do not respond as well to some treatments and have a poorer prognosis. As Dr. Heinz Ludwig, Center for Oncology and Hematology, Wilhelminenhospital, Vienna, Austria, pointed out, “To enable optimum therapy in patients with renal impairment, cancer therapy should be fast-acting and effective and patients will need good supportive care.” For such patients, bortezomib may be a therapeutic option because median time to response—39 days in the first two cycles—is fast. Another advantage in patients with renal impairment, according to Dr. Ludwig, is that response is independent of renal function.

Multiple Myeloma with Tandem Transplants

Summary

The growing number of elderly cancer patients demands appropriate action. This is a patient population with significant comorbidity that is often unable to withstand full-dose chemotherapy. It is therefore important to search for new therapies with better toxicity profiles. This is true for those patients affected by multiple myeloma.

Delegates here this week heard of promising new immunomodulatory therapies that can safely be added to standard chemotherapy. A clinical study was presented that provides important data on the efficacy and safety of the proteasome inhibitor bortezomib as part of first-line treatment in elderly patients who are unable to undergo autologous stem-cell transplantation. It was also demonstrated that the addition of thalidomide and, in particular, oral lenalidomide, to standard chemotherapy for multiple myeloma may also improve response.