All patients received a modified R-CHOP treatment with reduced doses of the following drugs: doxorubicin, 25 mg/m²; vincristine, 1 mg/m²; and cyclophosphamide, 400 mg/m². Rituximab and prednisone were given at standard doses (ie, 375 mg/m² and 40 mg/m² for 5 days, respectively). A prophylactic injection of pegfilgrastim was administered the day after chemotherapy. Cycles were administered every 3 or 4 weeks.

Results
All patients achieved a partial or complete remission. Three patients experienced severe infections requiring hospitalization. Two patients had congestive heart failure: one had decreased ventricular function and myocardial infarction, and the other experienced worsening of a preexisting chronic atrial fibrillation. None of our patients experienced severe cytopenias, mucitis, or renal or neurologic toxic effects. In 2 cases, the treatment had to be discontinued, and these patients died of adverse effects. The other 2 completed 6 cycles of treatment and at last follow-up (15 and 21 months) remained alive and in complete remission. Clinical data and outcomes are summarized in the Table.

View this table: [in this window] [in a new window] [as a PowerPoint slide]   Table. Clinical Data and Treatment Outcomes

Comment
In the overall population, the outcome of PCLBCL,LT is improved by R-CHOP, which is now considered the standard first-line treatment.^1-2 Alternative treatments such as radiotherapy or rituximab as single-agent therapy are proposed only if the condition of the patient does not allow R-CHOP treatment because these regimens have a lower complete response rate and a higher relapse rate.² Furthermore, radiotherapy is possible only for localized lesions.

Nevertheless, doxorubicin use is limited by cardiac toxic effects, which are known to be more frequent in elderly patients at lower cumulative doses.³ Moreover, elderly patients can have a lower tolerance of other chemotherapy toxic effects such as cytopenias, mucitis, and digestive adverse effects. In clinical practice, a reduction in doses can be made in consideration of the age of the patient, the presence of cardiopathy, and/or a poor general condition. Nevertheless, there is no consensus on the precise indications or amounts for this dose reduction.

In our patients, the doses were reduced based only on the age criterion. While we observed serious infectious and/or cardiac adverse effects in our 3 oldest patients, and 2 patients died of these complications, the other 2 achieved prolonged complete remission.

In our geriatric series, the expected efficacy of the treatment was counterbalanced by a poor tolerance of adverse effects, emphasizing the need for a pretherapeutic comprehensive geriatric assessment, which includes an evaluation of physiologic age, function, comorbidities, and nutritional, social, and economic needs.⁴ If this assessment shows that the patient is too fragile to receive standard treatment, less aggressive treatments should be discussed, such as radiotherapy or rituximab as single-agent therapy. Liposomal doxorubicin must also be evaluated in this indication.

Further clinical studies are needed to evaluate more precisely the outcomes of dose-reduced anthracycline-containing chemotherapy plus rituximab in elderly patients treated for PCLBCL,LT and to determine accurately its indications with regard to less aggressive treatments in this particular population.

AUTHOR INFORMATION
Correspondence: Dr Guyot, Hôpital Bichat, Service de Dermatologie, 46 rue Henri Huchard, 75877 Paris CEDEX 18, France (alexis.guyot{at}bch.aphp.fr).

Accepted for Publication: June 10, 2009.

Author Affiliations: Departments of Dermatology (Drs Guyot, Valeyrie-Allanore, and Bagot) and Pathology (Dr Ortonne), Henri-Mondor Hospital, APHP, Créteil, France; and Université Paris XII (Drs Guyot, Valeyrie-Allanore, and Bagot), Créteil.

Author Contributions: All authors had full access to all of the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Guyot, Ortonne, Valeyrie-Allanore, and Bagot. Acquisition of data: Guyot, Ortonne, and Bagot. Analysis and interpretation of data: Guyot, Ortonne, Valeyrie-Allanore, and Bagot. Drafting of the manuscript: Guyot, Ortonne, Valeyrie-Allanore, and Bagot. Critical revision of the manuscript for important intellectual content: Bagot. Study supervision: Bagot.

Financial Disclosure: None reported.