Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non-Hodgkin's lymphoma

Survival in patients with intermediate or high grade non-Hodgkin’s lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP

“…The Cox analysis (that considered the effect on survival of two variables: 'study', introduced as a categorical variable stratified on 5 levels, and 'treatment' introduced as a categorical variable stratified on 2 levels) calculated a relative death risk of 0.92 for third generation regimens vs. CHOP (95% CI: 0.80 to 1.06; P = 0.26). The study-specific values of relative death risk (Cox model) were not significantly different from one another (study by Wolf et al (1997): 1.00 with 95% CI of 0.86 to 1.17, P = 0.99; study by Fisher et al (1993): 1.02 with 95% CI of 0.91 to 1.14, P = 0.76; study by Montserrat et al (1996): 1.08 with 95% CI of 0.99 to 1.30, P = 0.42; study by Jerkeman et al (1999): 0.91 with 95% CI of 0.78 to 1.05, P = 0.20; all risk values calculated in comparison with the study by Gordon et al (1992) which was assumed to have death risk = 1); these data show that the inter-trial heterogeneity of the clinical material was acceptable. The meta-analysis plot based on crude death rates is shown in Figure 2.…”

“…The results of our inter-study comparison based on the Cox model showed that the heterogeneity across the 5 trials was not statistically significant; this finding therefore supports the reliability of our meta-analytical calculations. Among the 5 trials included in our analysis (Table 1), there were 4 negative studies (Gordon et al, 1992;Fisher et al, 1993;Montserrat et al, 1996;Jerkeman et al, 1999) together with a single positive study (Wolf et al, 1997) that found a survival improvement. The positive study has very similar characteristics in comparison with the others in terms of both patient selection criteria (very similar to the studies by Fisher et al (1993) and Montserrat et al (1996)) and type of aggressive chemotherapy (identical to the studies by Fisher et al (1993) and Jerkeman et al (1999)).…”

“…The survival information for these patients was derived from: a) Figure 2 for the study by Wolf et al (1997) (survival graphs based on the intention-to-treat approach); b) Figure 2 for the study by Fisher et al (1993) (survival graphs based on the intention-to-treat approach); c) Figure 1 for the study by Gordon et al (1992) (bytreatment analysis with no survival graph based on the intentionto-treat approach); d) Figure 4 for the study by Montserrat et al (1996) (survival graphs based on the intention-to-treat approach); e) the original raw data of survival in the case of the study by Jerkeman et al (1999) (data based on the intention-to-treat approach excluding those patients who were randomized in the absence of the inclusion criteria).…”

“…In the 2 trials by Gordon et al (1992) and Wolf et al (1997), the legends of the survival graphs provided complete information on the time distribution of deaths and on the time distribution of rightcensored patients. In the 2 trials by Fisher et al (1993) and by Montserrat et al (1996), the survival information was estimated by the approximate procedure described in Appendix 1.…”

“…On the other hand, the results of Phase-III randomized trials evaluating third generation schemes vs. CHOP (Gordon et al, 1992;Fisher et al, 1993;Cooper et al, 1994;Montserrat et al, 1996;Wolf et al, 1997;Jerkeman et al, 1999) have never been included in a systematic overview or in a meta-analysis.…”