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
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.
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 cisplatin/irinotecan.
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 paclitaxel/irinotecan?
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.
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 established regimens?
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.