Page 72 - Read Online

Table 2: OS risk factors This last value is much lower than that we have reported at
Univariate analysis 2-year in our study (70%) and suggests that the addition
P HR IC 95% of rituximab to GDP regimen significantly increases its
Sex 0.555 1.31 0.53-3.24 efficacy. However, an occurrence rate for grade III/IV
Age 0.289 1.74 0.62-4.85 leukopenia of 37.5% and 25% for thrombocytopenia
LDH 0.271 1.80 0.63-5.12 was found. These rates are higher than those we have
Stage 0.863 0.91 0.32-2.62 observed in our study and the reason is not clear. In
IPI 0.823 1.15 0.34-3.92
NPT 0.389 1.40 0.60-3.76 our study, 45 patients with aggressive refractory/relapsed
NPT: number of previous treatments; LDH: lactate dehydrogenase; DLBCLs not eligible for ASCT were treated with GDP-R
IPI: international prognostic index; OS: overall survival achieving an ORR of 48.8% with a median duration of
response of 13.59 months (range: 2.13-58.6 months).
Table 3: TTF risk factors Moreover, GDP-R resulted safe: no febrile neutropenia
Univariate analysis Multivariate analysis was recorded; grade-4 neutropenia was registered
P HR IC 95% B P HR IC 95% in one patient, and two patients developed grade-2
Sex 0.551 1.28 0.57-2.87 neurotoxicity. These data confirm GDP-R therapy is a
Age 0.536 1.37 0.51-3.66 reasonable option for refractory/relapsed DLBCLs in
LDH 0.290 1.59 0.67-3.76 patients who are not eligible for ASCT. In particular,
Stage 0.243 1.80 0.67-4.85 patients pre-treated with 2 or < 2 lines of therapy had a
IPI 0.041 2.82 1.01-7.87 1.29 0.048 3.65 1.24-10.7 better ORR than that of ones (63% vs. 22%) receiving
NPT 0.019 2.59 1.17-5.74 1.15 0.029 3.17 1.12-8.95 more than 2 lines before GDP-R, with a median TTF of
NPT: number of previous treatments; LDH: lactate dehydrogenase; 22.2 months vs. 2.7 months (P = 0.029 in multivariate
IPI: international prognostic index; TTF: time to treatment failure Cox model). Even IPI influenced TTF with a median of
17.3 months for patients with IPI value less or equal to
nucleoside analog. It is a competitive substrate with 2 and 3.4 months for patients with IPI > 2 (P = 0.048
deoxycytidine for incorporation into DNA, and in in multivariate Cox model). These data suggest that
this way, it inhibits DNA replication and repair. It is a exposition to numerous different chemotherapeutic
derivative of cytidine and even if it is similar to cytosine regimens selects chemoresistant neoplastic cells that
arabinoside, it can be absorbed by cells faster, more are difficult to be eradicated. Moreover, they suggest
effectively phosphorylated, and it remains in cells for a that within the entire population of patients with
longer of time. Gemcitabine inhibits the DNA synthesis refractory/relapsed DLBCLs not eligible for ASCT the
by preventing the activity of ribonucleotide reductase, number of previous chemotherapeutic regimens and
and this conduces to a reduction of the concentration of IPI value select those who benefit more from GDP-R
intracellular nucleotide pool. In this way, gemcitabine treatment. It is likely that the disease was intrinsically
has more antitumor activities and a lighter bone marrow more aggressive in patients with higher IPI index and
inhibition than higher dosage of cytosine arabinoside. [5,6] in those who required multiple chemo-treatments. In
As far as we know, one previous study [12] only has fact, tumor phenotype and its biological aggressiveness
been conducted using the same GDP-R regimen of are different in any cancer. In the multivariate analyses,
chemoimmunotherapy in patients with refractory/relapsed among the evaluated prognostic factors, the number
DLBCLs as in our report. In this study, in 50 successive of previous chemo-treatments and IPI index were
patients, the 2-year OS and progression-free survival significant variables for TTF. This finding suggests
were 70% and 48%, respectively. Hence, both these that the number of previous chemo-treatments and IPI
end-points was the same or similar to those we have are independent prognostic factors. Moreover, tumor
reported in our study. ORR was 72% and grade III-IV phenotype can change during the progression of the
neutropenia and thrombocytopenia occurred in 34% disease due to genetic instability of cancer cells. This
and 40% of patients. However, the schedule adopted by could account for the lack of a significant correlation
the investigators in this study was different than in ours. between the number of previous chemo-treatments
In fact, cisplatin was given at 25 mg/m IV on the days or IPI and OS. In fact, prognostic factors other than
2
1-3 instead of 75 mg/m on the day 1 and rituximab was the number of previous chemo-treatments and IPI
2
delivered on the day 1 instead of on the day 2. These and inherent to tumor phenotype can prevail with the
slight differences could have affected both ORR and progression of the disease.
toxicity that were higher than in our study. Moreover,
another previous study evaluated the efficacy of GDP In conclusion, the shown results, even if based on a
regimen given with the same schedule as in our study retrospective monocentric study and a small sample
but not including rituximab. [13] In this study, the ORR size, evidence that for patients with relapsed/refractory
was 58.3% for assessable patients, and the 1-year OS DLBCL, who cannot benefit from HDT and GDP-R is a
rate was 41.7%. reliable and well-tolerated therapeutic choice.

62
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ Issue 2 ¦ February 29, 2016 ¦