At the meeting in July 1999, symposium faculty also led sessions that
answered questions from the participants. New applications for the
management of small-cell lung cancer (SCLC) provide the focus for
these discussions, which followed each of the presentations.
Irinotecan in Small-Cell Lung CancerJapanese
TrialsMasahiro Fukuoka, et al
Question: If your randomized SCLC trial comparing
cisplatin/etoposide with cisplatin/irinotecan reveals a survival
advantage for the cisplatin/irinotecan arm, could
cisplatin/irinotecan become the new standard of treatment for
extensive SCLC in Japan?
Answer: The results of this study could provide strong
evidence of a survival advantage for cisplatin/irinotecan as initial
therapy for extensive SCLC. If so, we would want to confirm the
survival advantage with a second randomized study. Once confirmed,
the cisplatin/irinotecan regimen could become the new standard of
treatment in Japan.
Question: Can you comment on the incidence of grade 3/4
diarrhea in your studies?
Answer: The lower incidence of grade 3/4 diarrhea in the
Japanese studies could well be due to our aggressive use of a
prophylactic antidiarrheal regimen, or to our longer experience with
irinotecan, or both. However, since this safety variable was not
tested in our studies, the reasons for our success against severe
chemotherapy-induced diarrhea remain speculative.
Question: Would you comment on the impact of the randomized
trials of single-agent irinotecan and the combination of cisplatin
plus irinotecan in NSCLC?
Answer: There have been two randomized studies in metastatic
NSCLC. One study did not show an improvement in survival overall, but
a subset analysis of patients with stage IV NSCLC revealed a survival
advantage for the cisplatin/irinotecan combination. Additionally, the
results of the first study revealed that single-agent irinotecan was
comparable to cisplatin/vindesine in terms of overall survival
(Masuda N, Fukuoka M, Negoro S, et al: Proc Am Soc Clin Oncol
18:459a, 1999). The second phase III study (Niho C, Nagao Y,
Nishiwaki A, et al: Proc Am Soc Clin Oncol 18:492a, 1999) comparing
these combinations revealed no survival advantage for
Phase I/II Study of Weekly Irinotecan and Paclitaxel in Patients With
Small-Cell Carcinoma of the LungDaniel A. Rushing, MD
Question: Would you comment on the reporting of response rates
in your study? Specifically, how do the response rates compare, post
cisplatin/etoposide versus post cisplatin/etoposide and
Answer: In this study, the patients were pretreated with the
cisplatin/etoposide combination. The response to the pretreatment
combination was assessed first. Subsequently, after the patients
received the irinotecan combination, the response to both treatments
was assessed. This was done to evaluate improvement attributable to
the irinotecan combination. However, the study did not provide de
novo evidence of an advantage for the irinotecan combination.
Question: Would you consider reversing the order of the study
so as to better evaluate the response to the combination of
paclitaxel and irinotecan?
Answer: Yes, that would also be a reasonable approach. It
certainly would make sense to consider sequential therapy with these
combinations. No one knows which order is best. Giving the paclitaxel
and irinotecan combination up front would provide investigators
clearer evidence of efficacy in terms of response to that
combination. However, it is not clear that reversing the order of
treatments would have any effect on outcome.
Extensive Small-Cell Lung Cancer: A Treatment OverviewAlan
Question: It is difficult to compare the benefits of the new
combinations. Are any studies planned to compare new combinations
directly with each other, as opposed to new combinations versus
Answer: Not at this point. Research currently centers on
adding newer agents to the more traditional agents, such as the
ongoing Intergroup study for extensive SCLC that compares
cisplatin/etoposide vs cisplatin/etoposide/paclitaxel. Dr. Fukuoka
also recently completed a randomized trial of cispla-tin/etoposide vs
cisplatin/irinotecan (Noda K, Nishiwaki Y, Kawahara S, et al: Proc
Soc Clin Oncol 19:483a, 2000) that showed superior survival for
irinotecan plus cisplatin over standard etoposide plus cisplatin in
patients with extensive disease SCLC.