Delivery and Toxicity of Fludarabine-Based Combination Chemotherapy Regimens in Older Patients.

Fludarabine (F)-based combination chemotherapy regimens are highly effective in a range of indolent lymphoproliferative disorders. Despite the prevalence of such disorders in older patients, the deliverability of these regimes in patients aged >= 60 has not been assessed. We analysed the delivery and toxicity of three F-based regimens, all using F 25 mg/m2/dx3 q28d, in 82 adults aged >= 60 years, and compared this with the same regimens in 99 adults aged < 60. The sample comprised 66 patients (32 >= 60) treated with F and cyclophosphamide (C; 250 mg/m2/dx3); 29 with F and mitoxantrone (M; 10 mg/m2 x1; 12 >= 60); and 86 with FC and rituximab (R; 375 mg/m2 x1; 38 >= 60). 349 cycles in older patients were compared with 393 cycles in younger patients for haematologic nadirs, infectious complications and organ toxicity. Both groups received a median of 4 cycles, although older patients were more likely to require dose reduction (4.3% of cycles versus 1.2%, P < 0.001) and growth factor support (3.8% versus 1.8%, P=0.01). The cohorts were well matched for baseline characteristics other than age.

Overall, older patients had a slightly higher rate of infections (18%/cycle versus 15%/cycle), though this was not statistically significant (P = 0.28). For severe (grade >=3) infections the difference was minimal: 6% versus 7% (P< 0.5). The rates of neutropenia < 1.0 and 0.5 were 13% and 22% versus 11% and 20% for older and younger patients, respectively (all P values>0.1). The rates of thrombocytopenia < 100 and < 50 were 21% and 5% versus 16% and 5% for older and younger cohorts (all P values < 0.1). Other organ toxicities were uncommon, and showed no difference between age groups. Treatment-related mortality in both cohorts was <1% (P > 0.5).

Comparison within the cohort aged over 60 showed that those aged 70 and over were at higher risk of haematological and infectious toxicity. 82 cycles delivered to 23 patients aged >= 70 were compared with 267 cycles delivered to 61 patients aged 60 to 69. The rate of infection for those over 70 was 25% versus 16% in those aged 60 to 69, though this was not statistically significant (P=0.07). For severe infections (grade >=3), the rates were 13% versus 6% (P=0.03), while rates of neutropenia < 0.5 and thrombocytopenia < 50 were 32% and 15% versus 8% and 3% for those >= 70 and 60 to 69 respectively (all P values > 0.001).

These results demonstrate that F-based regimens are well tolerated and can safely be delivered to most older patients, with a modestly increased rate of infectious morbidity, but no increased treatment-related mortality. However, for patients aged >=70 the increased rate of toxicity mandates careful patient selection and monitoring.