Summary
Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were stored in a database and logistic regression analyses were performed to identify predictive factors for early death. During the first cycle, 118 out of 937 patients (12.6%) died. In 38 patients (4%), the cause of death was sepsis. Significant risk factors were age, performance status (PS), lactate dehydrogenase (LDH) and treatment with epipodophyllotoxins and platinum in the first cycle (EP). Risk factors for ENTD were age, PS and LDH. Extensive stage had a hazard ratio of 1.9 (P = 0.07). Risk factors for ETD were EP, PS and LDH, whereas age and stage were not. For EP, the hazard ratio was as high as 6.7 (P = 0.0001). We introduced a simple prognostic algorithm including performance status, LDH and age. Using a prognostic algorithm to exclude poor-risk patients from trials, we could minimize early death, improve long-term survival and increase the survival differences between different regimens. We suggest that other groups evaluate our algorithm and exclude poor prognosis patients from trials of dose intensification.
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References
Bork, E., Ersbøll, J., Dombernowsky, P., Bergman, B., Hansen, M. & Hansen, H. H. (1991). Teniposide and etoposide in previously untreated small-cell lung cancer: a randomised study. J Clin Oncol 9: 1627–1631.
Bork, E., Hirsch, F. R., Jeppesen, N., Lassen, U., Vallentin, S., Østerlind, K., Mejer, J., Ingeberg, S., Bergman, B. & Dombernowsky, P. (1997). Oral etoposide (VP-16) every 3 wks. or continuously to elderly patients with small cell lung cancer (SCLC). Preliminary results of a randomaized study. Lung Cancer 18: (suppl.1) 25
Fetscher, M., Brugger, W., Engelhardt, R., Kanz, L., Hasse, J., Frommhold, H., Wenger, M., Lange, W. & Mertelsmann, R. (1997). Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer. Ann Oncol 8: 49–56.
Girling, D. J., Hopwood, P., Lallemand, G., Machin, D., Stephens, R. J. & Baily, A. J. (1996a). Randomised trial of four-drug vs. less intensive two-drug chemotherapy in the palliative treatment of patients with small-cell lung cancer (SCLC) and poor prognosis. Br J Cancer 73: 406–413.
Girling, D., Thatcher, N., Clark, P. I., Hopwood, P., Twiddy, S. & Stephens, R. J. (1996b). Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Group. Lancet 31: 563–566.
Hirsch, F. R., Hansen, H. H., Hansen, M., Østerlind, K., Vindeløv, L. L., Dombernowsky, P. & Sörensson, S. (1987). The superiority of combination chemotherapy including etoposide based on in vivo small-cell lung cancer: a randomized trial of 288 consecutive patients. J Clin Oncol 5: 585–591.
Jackson, D. V., Case, L. D., Zekan, P. J., Powell, B. L., Caldwell, R. D., Bearden, J. D., Nelson, E. C., Muss, A. B., Cooper, M. R., Richard, SIIF, White, D. R., Cruz, J. M., Caponera, M. E., Furr, C. S., Spurr, C. L. & Capizzi, R. L. (1988). Improvement of long-term survival in extensive small-cell lung cancer. J Clin Oncol 6: 1161–1169.
Johnson, D. H., Einhorn, L. H., Birch, R., Vollmer, R., Perez, C., Krauss, S., Omura, G. & Greco, A. (1987). A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 5: 1731–1738.
Kalwinsky, D. K., Look, A. T., Ducore, J. & Fridland, A. L. (1983). Effects of the epipodophyllotoxin VP-16-213 on the cell cycle traverse, DNA synthesis, and DNA strand size in cultures of human leukemic lymphoblasts. Cancer Res 43: 1592–1597.
Katakami, N., Takada, M., Negore, S., Ota, K., Fujita, J., Aryoshi, Y., Ikegami, H. & Fukuoka, M. (1996). Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. Cancer 77: 63–70.
Klasa, R. J., Murray, N. & Coldman, A. J. (1991). Dose-intensity meta-analysis of chemotherapy regiments in small-cell carcinoma of the lung. J Clin Oncol 9: 499–508.
Kristjansen, P. E. G. & Hansen, H. H. (1990). Management of small cell lung cancer: a summary of the third International Association for the Study of Lung Cancer Workshop on Small Cell Lung Cancer. J Natl Cancer Inst 82: 263–266.
Lassen, U., Kristjansen, P. E. G., Østerlind, K., Bergman, B., Sigsgaard, T. C., Hirsch, F. R., Hansen, M., Dombernowsky, P. & Hansen, H. H. (1996). Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up. Ann Oncol 7: 365–371.
Lassen, U., Hirsch, F. R., Østerlind, K., Bergman, B., Dombernowsky, P. & Hansen, H. H. (1998). Outcome of combination chemotherapy in extensive stage small cell lung cancer. Any treatment related progress? Lung Cancer 20: 151–160.
Morittu, L., Earl, H. M., Souhami, R. L., Ash, C. M., Tobias, J. C., Geddes, D. M., Harper, P. G. & Spiro, S. G. (1989). Patients at risk of chemotherapy-associated toxicity in small cell lung cancer. Br J Cancer 59: 801–804.
Murray, N., Livingston, R. B., Shephard, F. A., James, K., Zee, B. C., Langle-Ben, A., Kraut, M., Bearden, J., Goodwin, J., Crafton, C., Turrisi, A. T., Walde, D., Croft, H. & Ottaway, J. (1997). A randomized study of CODE plus thoracic irradiation versus alternating CAV/EP for extensive stage small cell lung cancer (ESCLC). Proc Am Soc Clin Oncol 16: 456
Østerlind, K., Sörensson, S., Hansen, H. H., Dombernowsky, P., Hirsch, F. R., Hansen, M. & Rørth, M. (1983). Continuous versus alternating combination chemotherapy for advanced small cell carcinoma of the lung. Cancer Res 43: 6085–6089.
Østerlind, K., Hansen, H. H., Hansen, H. S., Dombernowsky, P., Hansen, M. & Rørth, M. (1986). Chemotherapy versus chemotherapy plus irradiation in limited small cell lung cancer. Results of a controlled trial with 5 years follow-up. Br J Cancer 54: 7–17.
Østerlind, K., Hansen, M., Hirsch, F. R., Dombernowsky, P., Sörensson, S., Pedersen, A. G. & Hansen, H. H. (1991). Combination chemotherapy of limited small cell lung cancer. A controlled trial on 222 patients comparing two alternating regimens. Ann Oncol 2: 41–46.
Pedersen, A. G., Østerlind, K., Vindeløv, L., Sörensson, S., Hansen, M., Dombernowsky, P. & Hansen, H. H. (1987). Alternating or continuous chemotherapy of small cell lung cancer. A three armed randomized trial (abstract). Proc Am Soc Clin Oncol 6: 187
Pfluger, K-H, Schmidt, L., Merkel, M., Jungclas, H. & Havemann, K. (1987). Drug monitoring of etoposide (VP16-213). Correlation of pharmacokinetic parameters to clinical and biochemical data from patients receiving etoposide. Cancer Chemother Pharmacol 20: 59
Radford, J. A., Ryder, W. D. J., Dodwell, D., Anderson, H. & Thatcher, N. (1993). Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis. Eur J Cancer 29A: 81–86.
Souhami, R. L., Spiro, S. G., Rudd, R. M., Ruiz De Elvera, M. C., James, L. E., Gower, N. H., Lamont, A. & Harper, P. G. (1997). Five-day oral etoposide treatment for advanced small-cell lung cancer. Randomized comparison with intravenous chemotherapy. J Natl Cancer Inst 89: 577–580.
SPSS for Windows Statistical package, version 6.1.3, (1995).
Stahel, R. A., Takvorian, R. W., Skarin, A. T. & Canellos, G. P. (1984). Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU, and VP-16 in small cell carcinoma of the lung and a review of the literature. Eur J Cancer Clin Oncol 20: 1233–1238.
Stephens, R. J., Girling, D. J. & Machin, D. (1994). Treatment related deaths in small cell lung cancer trials: can patients at risk be identified?. Lung Cancer 11: 259–274.
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Lassen, U., Østerlind, K., Hirsch, F. et al. Early death during chemotherapy in patients with small-cell lung cancer: derivation of a prognostic index for toxic death and progression. Br J Cancer 79, 515–519 (1999). https://doi.org/10.1038/sj.bjc.6690080
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DOI: https://doi.org/10.1038/sj.bjc.6690080
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