Questions and Answers: Non–Small-Cell Lung Cancer

At the meeting in July 1999, symposium faculty also led sessions that answered questions from the participants. New applications for the management of non–small-cell lung (NSCLC) cancer provide the focus for these discussions, which followed each presentation.

Overview of Metastatic NSCLC—Alan Sandler, MD

Question: What are the most favorable prognostic factors for patients with metastatic non–small-cell lung cancer?

Answer: In a retrospective multivariate analysis of clinical trials in advanced non–small-cell lung cancer conducted by ECOG from 1981 to 1992, the following prognostic factors were identified statistically as favorable: ECOG performance status of 0, absence of metastatic disease symptoms, normal appetite, and absence of bone or hepatic metastases. (Jiroutek M, Johnson D, Blum R, et al: Proc Am Soc Clin Oncol 17:461a, 1998.)

Question: Can you discuss some of the novel noncytotoxic antineoplastic agents in development?

Answer: There is a wide range of new agents under development. An important new group, the angiogenesis inhibitors, inhibit the development of new blood vessels that tumors require for growth. This group includes Endostatin and Angiostatin, agents developed by Judah Folkman at Harvard. These agents are currently being evaluated in phase I clinical trials. Genentech has developed anti-VegF, an antibody directed against vascular endothelial growth factor. In addition, the metalloprotease inhibitors such as marimostat have some anti-angiogenesis activity and also diminish the likelihood of metastases. Signal transduction modifiers are also under development and are related in function to the angiogenesis and metallopro-tease inhibitors. All of these agents derive from research in and broader understanding of cell biology.

Phase I–II Trial of Irinotecan, Carboplatin, and Paclitaxel in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer—Ronald Natale, MD, et al

Question: Your results are intriguing, yet the dose of irinotecan (100 mg/m² q 3 weeks) is rather small. Do you suspect some drug-drug synergy (ie, could irinotecan or its metabolite SN-38 be acting as a modulator)?

Answer: The results could have been due to drug-drug synergy, but this cannot be certain. If there were a drug-drug interaction, it occurred as a result of an intracellular modulation of either carboplatin or paclitaxel, as happens when leucovorin is added to 5-FU. On the other hand, the pharmacokinetics of either carboplatin or paclitaxel could have had an impact on irinotecan or its metabolite, SN-38. However, because pharmacokinetics were not evaluated in this study, there really is no way to answer this question definitively.

Evolution of Combined Modality Therapy for Stage III Non–Small-Cell Lung Cancer—David Gandara, MD, et al

Question: It is clear that the addition of chemotherapy to radiotherapy is superior, in terms of survival, to radiotherapy alone. Would you comment on whether concurrent or sequential chemoradiotherapy is superior?

Answer: Until recently there have been no studies comparing concurrent and sequential chemoradiotherapy. However, a recent study by Fukuoka showed a survival advantage for concurrent combined modality therapy. (Andoh T, Ishii K, Suzuki Y, et al: Characterization of a mammalian mutant with a campothecin-resistant DNA topoisomerase I. Proc Natl Acad Sci USA 84:5565-5569, 1987.) The study involved just over 300 patients and used split-course rather than continuous radiation therapy. Another recently completed study sponsored by the RTOG compared the Dillman regimen with cisplatin and vinblastine given sequentially versus another arm that incorporated the same therapy given concurrently, and a third arm in which the patients received cisplatin and oral etoposide with concurrently administered hyperfractionated radiotherapy. The results of this study will be presented at ASCO 2000. (Curran W, Scott C, Langer R, et al: Proc Am Soc Clin Oncol 19:484a, 2000.)

Outpatient Weekly Irinotecan and Concurrent Radiation Therapy for Stage III Unresectable NSCLC: A Vanderbilt-Ingram Cancer Center Affiliate Network (VICCAN) Trial—Hak Choy, MD

Question: Would you comment on the incidence of pneumonitis in your study as compared to other studies with irinotecan and radiotherapy?

Answer: This was the first study of concurrent radiochemotherapy in which there was no fatal pneumonitis. This may have been due to the small number of patients enrolled (13) and the small tumor volume irradiated in this study. Also, the investigators attempted to limit the radiation exposure to preserve lung tissue. There are too many variables and too few patients to arrive at any meaningful conclusions about the absence of pneumonitis in this study. Further studies are needed to address this question.

Question: Could you describe the treatment volumes in your study and compare them to other studies examining the newer agents with concurrent radiotherapy (eg, the CALGB trial)?

Answer: The initial volume of 4,000 Gy was directed at tumor in the mediastinum; the boost to the primary that involved the nodes was 2,000 Gy. All of it was given at 200 Gy per fraction. This is consistent with standard treatment and is similar to other studies.