autologous blood and marrow transplantation - Blog Science ...

Elias et al.
(CAV) and with etoposide (CAE), but not etoposide and cisplatin (EP), were
associated with a longer median survival in extensive-disease patients. The relative
range of doses administered and response and survival advantages were modest. 10
Seven randomized trials have tested the role of dose intensity in SCLC, almost
exclusively in the extensive-stage setting. 11-17
The actual delivered doses when
reported were significantly less different between the arms than the planned dose
intensity differences (1.2- to 2-fold). Three of these trials showed a modest survival
advantage for the higher-dose therapy. Arriagada et al. treated LD patients with six
cycles of conventional dose chemotherapy wherein the first cycle only was
randomly assigned conventional dose vs. modest intensification. 17
A complete
response and survival advantage for the patients receiving the intensified
chemotherapy was remarkable, since the relative difference in the two groups was
so small. While this result could reflect chance, it is possible that dose intensity,
particularly if given early in the course of treatment, may be more effective in the
limited- rather than the extensive-stage setting. Early intensification and treatment
of earlier stage disease are two themes to consider when designing new trials.
Multidrug cyclic weekly therapy was designed to increase the dose intensity of
treatment by taking advantage of the differing toxicities of the weekly agents.
Although patient selection effects were evident, early phase II results were quite
promising. 18
' 19
No survival benefits were documented in the randomized trials, 20-23
perhaps related to the greater dose reductions and delays required for the weekly
schedules compared with every-3-weeks conventional therapy, thus the actual
delivered dose intensities were not that different. Moreover, not only were doses and
schedules varied, but so were the regimens, leading to interpretation obstacles.
Follow-up is still too limited to evaluate late disease-free survival plateau differences.
Currently established cytokines (e.g., granulocyte and granulocyte-macrophage
colony-stimulating factors [G-CSF and GM-CSF]) were able to maintain dose
intensity across multiple cycles 24
without demonstrable survival advantage. With
cytokine use, a modest increment in dose intensity, limited by cumulative thrombocytopenia,
can be achieved (1.5- to 2-fold). The effectiveness of various
thrombopoietins or other cytokines to increase achievable dose intensity remains
uncertain. The underlying cardiovascular and pulmonary comorbidity, median age
of 60-65 years, and enhanced risk of secondary smoking-related malignancies
inherent in lung cancer patients contribute to an increased risk when applying doseintensive
therapy.
DOSE INTENSITY: WITH CELLULAR SUPPORT
This summary includes older trials of patients with SCLC undergoing
autologous bone marrow transplantation (autoBMT) if specifics about their
response status (relapsed or refractory; untreated; or responding to first-line
403