A Retrospective Study On the Efficacy of Relative Dose Intensities of Non-Hodgkin's Lymphoma Treatments: Response to Chemotherapy and Overall Survival.

A common problem with chemotherapy treatments is reduced dose-intensities from treatment delays due to chemotherapy induced toxicities. In 2004, Lyman and colleagues assessed the overall incidence of reduced dose-intensities for 4,522 non-Hodgkin's lymphoma (NHL) patients. They determined that 53% of the patients, due to treatment delays of >7 days (24%) or reduced doses of >15% (40%), received a relative dose intensity (RDI) of <85% compared to NCCN standard dosage, with a mean RDI of 80.57% and a median of 86.48% (Lyman et al 2004 J Clin Onc). A similar study conducted by Lepage et al found 28% of 311 lymphoma patients were treated with <70% of the standard NCCN dose. These patients exhibited decreased chemotherapy response rates and shorter 2 year survival rates, with 61% surviving two or more years compared to 72% of patients getting >70% RDI (Lepage et al 1993 Annals Onc). In light of these studies, we conducted a retrospective chart analysis to assess the average RDI for NHL patients treated at our outpatient oncology clinic between 2006 and 2008, and determine if RDIs had a noticeable impact on patient responses to treatment.

The primary objective of our chart review was to calculate the delivered dose intensities of chemotherapy for 60 NHL patients, and determine if a higher RDI resulted in better responses to chemotherapy and 2 year survival rates. We included only patients who received the 21-day cycle cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen, Rituximab-CHOP (R-CHOP) regimen, cyclophosphamide, vincristine, prednisone and rituximab (R-CVP) regimen, or the 14-day cycle R-CHOP regimen. Patients received between 3 and 8 cycles of chemotherapy over a period of 2 to 4 months. We calculated RDI by entering the dates of each cycle of chemotherapy, and the dose delivered of each drug in the regimen, into the Nearspace Inc. RDI calculator (http://www.nearspace.com/medical%2Dcalculator/rdi/). Any delays and/or reductions in the dosage (compared to the standard NCCN 21 or 14 day cycle CHOP/CVP regimen dosages) would result in a lower overall RDI.

Twelve (25%) of the 60 NHL patients received an RDI of less than 85%, and 5 patients (8.3%) received less than 70% of the standard NCCN dose. Nine patients (15%) received dose reductions of >15% and 10 patients (17%) had treatment delays of >7 days. The mean RDI was 91% and the median was 95%. There was minimal difference between the average RDIs for the treating regimens (CHOP = 91%, R-CHOP 14 = 91%, R-CHOP 21 = 91% and R-CVP = 88%). Patients over the age of 65 received an average RDI of 85% whereas patients under the age of 65 received an average RDI of 94%. Stage I patients (n=10, 16.7%) received an average RDI of 95%, stage II patients (n=11, 18.3%) received an average RDI of 90%, stage III patients (n=17, 28.5%) received an average RDI of 92%, and stage IV patients (n=22, 36.5%) received an average RDI of 87%. Forty-seven patients (78.3%) had a complete response to chemotherapy (average RDI = 92%), 4 patients (6.7%) exhibited a partial response (average RDI = 90.75%), 5 patients (8.3%) showed signs of stable disease (average RDI = 80.6%), and 4 patients (6.7%) had progressive disease (average RDI = 91%). The overall 2 year survival rate for all patients was 93.3%: the survival rate of patients with RDIs <85% and patients with RDIs >85% were both 93.3%.

Both the mean and median RDI we found were higher than those found in the study by Lyman et al (91% and 95% respectively compared to 81% and 86%), and only 25% of patients received <85% RDI compared to 53% of patients in the study by Lyman and colleagues (Lyman et al 2004 J Clin Onc). The average RDI for our 60 patients was higher than that noted in previous studies (91% vs. 80.57% and 79%), and the overall 2 year survival rate was also correspondingly increased (93.3% vs. 61%) (Lepage et al 1993 Annals Onc; Lyman et al 2004 J Clin Onc). Our study is limited by its small sample size, and is inconclusive regarding whether a RDI of above or below the NCCN standard 85% does impact overall survival (both lower and higher RDI groups had a 93.33% survival rate). However we did find that fewer reduced doses and/or delayed treatments does in fact increase overall 2 year survival rates (93% compared to 72%, Lepage et al 1993) and had a positive impact on chemotherapy responses (87% exhibiting a complete response compared to 53%, Lyman et al 2004). Our study highlights the significance of limiting dose delays and reductions in chemotherapy regimens in order to improve patient responses.

No relevant conflicts of interest to declare.